Marc In het Panhuis, University of Wollongong
Namita Choudhury, RMIT University
Ferenc Horkay, National Institutes of Health
Jurgen Groll, University of Wurzburg
SB04.01: 3D and 4D Printing I
Marc In het Panhuis
Monday AM, December 02, 2019
Hynes, Level 3, Room 302
8:00 AM - SB04.01.01
Phase-Separating Biopolymer Conjugates in Designing Multicomponent Biomaterials
University of Delaware1Show Abstract
Microstructured hydrogels offer many opportunities in developing therapeutic matrices for guiding cell behavior. This presentation will outline our recent studies in formulating PEG- and (poly)peptide-based conjugates with nanoscale and microscale structures imparted by the controlled phase separation of multicomponent solutions. Resulting microstructured hydrogels can be manipulated on the basis of solution conditions and the composition of the polypeptide. The materials exhibit distinct microscale mechanical properties (1-15kPa) in ranges relevant for the development of synthetic pedicles for vascular grafts and high cytocompatibility over weeks in static and dynamic culture. Given our observations that the activation of fibroblasts and the differentiation of CD34+ stem cells can be directed in substrates with shear storage moduli in this range, our data suggest possible cell-materials platforms for modulating the activities of cells relevant in cardiovascular applications.
8:30 AM - SB04.01.02
3D-Extrusion Printing of Stable Constructs Composed of Polypeptide Hydrogels
Andreas Heise1,Robert Murphy1
Royal College of Surgeons in Ireland1Show Abstract
The field of tissue engineering and regenerative medicine aims to regenerate damaged tissues rather than their replacement via the creation of well defined, surgically implantable biomaterial constructs.The development of defined three-dimensional (3D) architecture fabrication for tissue engineering has been a recent emergence within the field. In particular, 3D printing represents a promising rapid prototyping technology for the production of intricate bio-inspired scaffolds/constructs. The primary feedstock materials used are polymeric hydrogels, which possess ideal physicochemical properties for these rapid 3D patterning techniques. Hydrogels encompass the capability to augment native tissue due to their comparative 3D nano-architecture while holding the potential to act as a mimetic of the extracellular environment. Recent work on 3D rapid prototyping with hydrogels has mainly focused on the use of natural polymers. Polysaccharides such as chitosan have been chemically functionalized and used as carriers within hydrogel inks. Recent reports also detail the fabrication of modified bio-native gelatin hydrogels which were 3D printed into cell laden constructs and self-healing structures respectively. More synthetic approaches have utilized poly(ethylene glycol) or acrylic monomer loaded inks. Despite these efforts, the limited number of suitable bio-inks has been identified as the major barrier to progress and the development of new advanced hydrogel applications.
We present a new family of copolypeptide based hydrogel ink capable of structural microfabrication using 3D extrusion printing. The material comprises an amphiphilic block or star copolymer structure which spontaneously form hydrogels through hydrophobic interaction. The chemical design allows the bulk phase of the hydrogel to remain intact after application of shear due to its self-recovery behavior. It is demonstrated that the composition of the materials is ideally suited for 3D printing; with scaffolds capable of maintaining structural cohesion after extrusion. Post extrusion UV-triggered fixation of the printed structures can be carried out resulting in stable hydrogel constructs. The constructs were found to be degradable, exhibited favorable release of encapsulated molecular cargo and did not affect the metabolic health of the commonly used fibroblastic cell line, Balb/3T3 cells. Moreove, the functionality of the amino acid building block allows the design of intrinsically antimicrobial constructs. In summary, the copolypeptide inks offer a new bioink platform that allow for rapid prototyping enabling the fabrication of defined intricate microstructures, providing a platform for complex scaffold development.
9:00 AM - SB04.01.03
3D Bio-Printed Platforms for Oral and Dental Diseases
American Dental Association1,National Institute of Standards and Technology2Show Abstract
Traditional treatments for periodontal and dental diseases have severe limitations, including high-cost, non-efficient drug delivery, and aging. For example, patients who receive tooth and gum grafts are subject to lifelong side-effects, such as increased rates of gum infections and oral malignancies. A solution to overcome these barriers is the integration of oral medicine and bioengineering within a single framework for potential translational and therapeutic purposes of dental diseases. Our lab focuses on identifying new biological targets involved in periodontal disease with the development of multidisciplinary tools, including organ-on-a-chip technologies, oral biology, and 3D printing technology. Our particular focus for today’s presentation is diabetes on oral health. Diabetes is a chronic, incurable disorder characterized by lack of resistance to insulin, leading to an excess of serum glucose, which negatively affects homeostasis of the oral epithelium [1,2]. Alterations or disruptions of the epithelial integrity can ultimately result in chronic inflammation and periodontal disease. We engineered a 3D platform to deconvolute the dynamic contribution of epithelium in diabetic periodontitis. The in-vitro disease epithelium model is a 3D printed microfluidic platform that is comprised of 3D cylindrical channel (diameter 160 µm) embedded within different stiffnesses (0.1kPa, 1kPa, 10kPa) of hydrogel solution of collagen I. Human oral keratinocytes (HOKs) were seeded and allowed to adhere through the collagen I wall. The epi-oral tube was exposed to 11 nmol/ml glucose to mimic diabetic conditions compared to control, 4 nmol/ml glucose under different stiffnesses. In addition, we introduced a pro-inflammatory stimulus into the 3D bio-printed platform, named lipopolysaccharides (LPS) (100 ng/ml) for 1hr. The diffusion of fluorescent dextran (70 kDa Texas Red, Thermo Fisher) (12.5 μg/mL) was imaged in real time with a confocal microscope (LSM 800, Carl Zeiss). The diffusive permeability coefficient (Pd) was calculated by measuring the flux of dextran into the collagen gel and fitting the resulting diffusion profiles to a dynamic mass conservation equation . The Pd was increased dramatically in LPS treated diabetic conditions compared to non-diabetic ones. Finally, LPS treatment increases FOXO1 translocation in diabetic HOKs. Collectively, the 3D bioengineered micro-platforms substantial provide insights on periodontitis area by developing sophisticated approaches, based on the 3D printing and organ-on-a-chip technology, avoiding the limitations of the 2D standard cell culture and enabling us to approach potential efficient treatments for periodontal diseases.
10:00 AM - SB04.01.04
3D Printing of Transparent and Conductive Heterogeneous Hydrogel-Elastomer Systems
Harvard University1Show Abstract
Interest in stretchable electronics has grown significantly in recent years, driving a need for soft and stretchable materials that can sustain high strains and still fulfill their function in applications such as wearable sensors for health monitoring or feedback sensors in soft robotics. Many stretchable conductors exist including liquid metals, nanowires, and micro-cracked metals. Conventional strategies of incorporating hard components with soft elastomers to attain stretchability often lead to failure of the hard-soft material interface and limited stretchability. The use of gels as soft conductors, where ions are the charge carriers instead of electrons, represents an entirely different approach that has gained popularity recently. Their high stretchability, when combined with recent improvements in toughness and stiffness, enable their use as stretchable electrical conductors, capacitive strain sensors, and chemical/pH sensors. Gel-based ionic circuits thus represent a unique class of devices within stretchable electronics. Fabrication of stretchable electronics using hydrogels requires integrating hydrogels with stretchable dielectrics such as dielectric elastomers; a process thus far achieved primarily via the combination of several different manufacturing techniques. We have developed an extrusion printing technique capable of fabricating an ionic circuit that integrates a LiCl-doped poly(acrylamide) (PAAm) hydrogel with a poly(dimethylsiloxane) (PDMS) dielectric elastomer. By incorporating hygroscopic salts such as LiCl into the hydrogel, we are able to prepare an ionically conductive hydrogel with excellent water-retaining properties. For printing reliability, we have optimized the rheological properties of a high ionic-strength hydrogel precursor using a nonionic rheological modifier. We show that the adhesion between oxygen plasma-treated PDMS and hydrogel increases with time to reach a stable value of 15 J m−2 after approximately six days. During that time, the contact angle of water on the PDMS interface remains constant at 30°, suggesting that hydrophobic recovery of plasma-treated PDMS is suppressed by the presence of the hydrogel. Furthermore, a thin viscous layer develops at the interface between PDMS and hydrogel, which results in energy dissipation upon debonding and which allows full recovery of the adhesion after debonding and rejoining. Finally, we demonstrate the viability of silane coupling agents to further enhance the adhesion between PDMS and hydrogel. By introducing a charge-neutral surfactant in the PDMS and adjusting silane concentrations in the PAAm, interfacial adhesion can be increased to the point that the system fails by cohesive failure within the hydrogel, achieving toughness values of up to 193 J m−2 for a fully printed PAAm hydrogel-on-PDMS bilayer. This result suggests that an integration strategy with silane coupling agents may enable robust extrusion printing of a wide variety of hydrogel and silicone elastomer chemistries.
10:30 AM - SB04.01.05
Stereolithographic 3D Printing of Self-Adhesive Double Network Hydrogels for Soft Actuators and Microfluidics
Eric DuBois1,Thomas Valentin1,Catherine Machnicki1,Dhananjay Bhaskar1,Francis Cui1,Ian Wong1
Brown University1Show Abstract
Hydrogel building blocks that are stimuli-responsive and self-adhesive could be utilized as a simple “do-it-yourself” construction set for soft machines and microfluidic devices. However, conventional covalently-crosslinked hydrogels are unsuitable since they are as static materials with poor interfacial adhesion. Here, we demonstrate ion-responsive interchangeable parts based on composite hydrogels that incorporate both covalent and ionic crosslinking. We use light-directed 3D printing to covalently-crosslink poly(ethylene glycol) diacrylate in the presence of anionic poly(acrylic acid) of much higher molecular weight. The addition of trivalent cations acts to crosslink the anionic polymer chains together. Using high cation concentrations drives strong crosslinking, which can result in dramatic hydrogel contraction. Mismatched contraction of layered ion-responsive and non-ion-responsive hydrogels can control bending and twisting actuation, which is utilized for a gripping device. Alternatively, moderate cation concentrations permit strong self-adhesion between hydrogel surfaces. LEGO-like hydrogel blocks with internal channels and external mechanical connectors can be stacked into complex microfluidic device geometries including serpentine micromixers and multilevel architectures. This approach enables “plug-and-play” hydrogel parts for ionic soft machines that mimic actuation, sensing, and fluid transport in living systems.
10:45 AM - SB04.01.06
3D Printing of Biocompatible and Structurally Relevant Hydrogel Scaffolds for Articular Cartilage Tissue Engineering
Mahmoud Amr1,Joshua Kernan2,Alia Mallah1,Terreill Robertson3,Haneen Abusharkh2,Olivia Reynolds2,Arda Gozen2,Bernard Van Wie2,Juana Mendenhall3,Vincent Idone4,Nehal Abu-Lail1
The University of Texas at San Antonio1,Washington State University2,Morehouse College3,Regeneron Pharmaceuticals Inc4Show Abstract
Osteoarthritis (OA) is a disease that affects more than 30 million adults in the US, posing a huge economical burden and adversely affecting people’s lifestyle. It is the hallmark of the degradation of Articular Cartilage (AC) lining moving joints, due to systemic, genetic, and injury related causes. One of the most prevalent types of OA is knee OA. Knee OA can cause enormous pain and discomfort and may lead to disability. No current single efficient treatment exists for knee OA. The disease is managed through pain killers, anti-inflammatory drugs, hyaluronic acid injections, and eventually a total knee replacement (TKR). Tissue Engineering (TE) offers an alternative route that is potentially capable of managing or treating OA while avoiding the limitations associated with OA’s traditional treatment routes. In TE, cells are seeded on a scaffold and grown in a bioreactor under a controlled environment in vitro. Ideally, the bioreactor is supplied with nutrients and built to mimic the mechanical shear stress, compression and oscillation pressures present in the knee. The product of interest of a TE approach is a functional AC tissue that mimics the native one in structure and function. AC has a unique structure that consists of three different zones (superficial, intermediate, and deep). Each zone is characterized by its own cellular and protein composition, fibrillar alignment, porosity and mechanical strengths. The variations in the zonal properties allow each zone to serve a specific AC function including lubrication and loadbearing. To our knowledge there is no current AC tissue engineered that mimics the native AC in structure and function. In a step towards replicating the AC unique zonal structure, we hypothesize that a structurally relevant scaffold that mimics the gradated anatomy of the native AC will guide the chondrocytes to create a native-mimicking tissue that can be used as an alternative to traditional cartilage grafts. Onto test our hypothesis, a biocompatible, biodegradable, and structurally relevant gradated scaffolds in composition, porosity and mechanics will be fabricated using 3D printing and optimized via testing in a bioreactor for appropriate AC growth. Our scaffolds are hydrogels consisting of Gelatin (GEL), Gum Arabic (GA), and Sodium Alginate (SA) mixed in different concentrations and crosslinked by cooling, Calcium Chloride (CaCl2), 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-Hydroxysuccinimide (NHS) respectively to achieve a mechanically stable structure. To print the scaffold, we have modified the commercial 3D bioprinter BioX from Cellink with a pressure amplifier and a home-made software control to achieve high printing pressure and time-efficient printing of scaffolds with different printing parameters. With that, we have been able to 3D print scaffolds with line width as fine as 250 µm using a 100 µm nozzle and a pressure of 700 kPa at room temperature using the hydrogel composed of (8.2% GA, 4.2% GEL, 8.2% SA). When bovine chondrocytes were cultured on the hydrogels for 14 days, they were viable. Biochemical assays confirmed that the cells with their pre-mature tissue expressed AC-specific biomarkers such as glycosaminoglycan (GAGs) and total collagen. To improve on our current findings, ongoing work aims at characterizing the ultimate tensile strength, elastic modulus, and hardness of the structural scaffolds using a universal testing machine. We hypothesize that the resulting AC tissue will have better native-mimicking AC structure and function when the mechanical properties of the scaffold mimics those of the native AC ECM properties. Ultimately in the future, the 3D printed structural scaffold combined with cell-laden hydrogels will be grown in a unique centrifugal bioreactor to create a mechanically and biologically native-mimicking AC tissue.
11:00 AM - SB04.01.07
A Mechanically Enhanced Electroactive Hydrogel for 3D Printing Using a Multileg Long Chain Crosslinker
Yong-Woo Kang1,Jaesung Woo1,Hae-Ryung Lee1,Jeong-Yun Sun1
Seoul National University1Show Abstract
Electroactive hydrogels (EAHs) are receiving attention in soft robotics. 3D printing makes EAHs even more attractive, due to the diversification and elaboration of actuations. However, 3D printing needs a large amount of photoinitiator for faster printing, which makes the printed hydrogels so brittle that they cannot produce large scale 3D printing. Here, we developed a 3D printable EAH based on poly(3-sulfopropyl acrylate, potassium salt) (PSPA) using glycidyl methacrylated hyaluronic acid (GMHA) as a mechanically enhancing multileg long chain (MLLC) crosslinker. The MLLC crosslinking improved the stretchability of the PSPA-based hydrogel to 49% from 28%, while maintaining the same level of electroactivity. Additionally, the fracture toughness of the PSPA-based hydrogel remarkably increased from 11 J/m2 to 40 J/m2 with crosslinking by the MLLC. Using the mechanically enhanced EAH, i.e., the GMHA-PSPA EAH, the 3D printing of elaborate structures, e.g., ‘Leaning Tower of Pisa’ and a hand, and their electroactuation were successfully demonstrated.
11:15 AM - SB04.01.08
3D Printing of Programmable Microbial Hydrogels
Avinash Manjula Basavanna1,2,Anna Duraj-Thatte1,2,Neel Joshi1,2
Wyss Institute for Biologically Inspired Engineering1,Harvard University2Show Abstract
Over the years, 3D printing technology has witnessed the development of numerous inks and bioinks for various applications. Bioinks are especially challenging as it requires biocompatibility, resembling microenvironment that favors cellular viability/adhesion, adequate mechanical properties and the capabilities for chemical/photochemical functionalization. Building on these characteristics and advances, herein, we present programmable living inks comprising of microbial hydrogels. Our innovative strategy provides unprecedented control on the characteristics of the ink as well as the ability to systematically regulate the microbes embedded in the 3D patterns.
11:30 AM - SB04.01.09
Nanoscale Hydrogel 3D Printing with Focused Electron Beam
Andrei Kolmakov1,Tanya Gupta1,2,Glenn Holland1,Evgheni Strelcov1,2,Joshua Schumacher1,Yang Yang1,2,Mandy Esch1,Vladimir Aksyuk1
National Institute of Standards and Technology1,University of Maryland2Show Abstract
Additive manufacturing of hydrogel scaffolds has become the key technology for tissue engineering, soft robotics, biosensing, drug delivery and biomedical research in general. The progress in the field has been advanced via development of special polymerization initiators coupled with modern additive manufacturing techniques. The current state of the art 2-photon, and stereolithography curing techniques allow for 3D printing of submicron scale hydrogel features. Further advancement in printing time and resolution could be envisioned by using curing radiation with shorter wavelength and larger crosslinking cross-section. Despite of highly developed electron, ultraviolet and X-ray lithography of dry polymers to pattern nanoscopic features, 3D printing from liquid hydrogel precursor solutions is hard to realize due to vacuum incompatibility of liquid samples. In this work we resolve this “pressure gap” impediment and demonstrate a technique for in-liquid hydrogel 3D-sculpturing using fluidic enclosures equipped with electron transparent windows. The principle of the technique, details of the curing mechanism and factors affecting the ultimate feature size (resolution), are described and validated through the comparison of experiments and simulations. The potential of this technique is demonstrated on few selected examples such as live-cell encapsulation, synthesis of nanocomposite hydrogels and microfabrication of mesoscopic 3D-hydrogel structures.
11:45 AM - SB04.01.10
Matrix Assisted 3D Printing of Cellulose Nanofiber Hydrogels
Sungchul Shin1,Jinho Hyun1
Seoul National University1Show Abstract
In the matrix assisted 3D printing, rheological properties of materials are of importance for the formation of highly resolved structures. The concentration of hydrophobically modified-CNF (Hphob-CNF) and hydrophilic-CNF(Hphil-CNF) hydrogels was fixed at 1%, and petroleum-jelly was mixed with liquid paraffin at a ratio of 3: 1 for the 3D printing. The viscosity change of hydrogels and petroleum-jelly ink showed a shear thinning behaviour, which was an important parameter for the easy extrusion of ink in direct ink writing. The Hphob-CNF hydrogel continued to show a high colloidal stability without any stabilizer as the Hphil-CNF hydrogels showed. It is considered that the viscosity of CNF hydrogels is mainly determined by the aspect ratio of fibers, the number of ends and the branch of fibers rather than the surface property of high aspect ratio of nanofibers. The sol-gel transfer properties of Hphob-CNF matrix and Hphil-CNF ink exhibited elastic properties over a wide range of shear stress, making it very useful as a printing matrix and a printing ink. Channel forming petroleum-jelly ink also showed the elastic properties confirming the stability in printing. The applicability of the CNF hydrogels embedding microchannels will be introduced in the presentation.
SB04.02: Biomedical Applications
Monday PM, December 02, 2019
Hynes, Level 3, Room 302
1:30 PM - *SB04.02.01
Granular Hydrogels for Biomedical Applications
University of Pennsylvania1Show Abstract
Hydrogels represent a class of biomaterials that have great promise for the repair of tissues, particularly due to our ability to engineer their biophysical and biochemical properties. Hydrogels can provide instructive signals through material properties alone (e.g., mechanics, degradation, structure) or through the delivery of therapeutics that can influence tissue morphogenesis and repair. In recent years, we have transitioned from traditional hydrogels to granular hydrogels that are comprised of smaller hydrogel units (i.e., microgels). Granular hydrogels have advantages in that they can be designed through heterogeneous microgels to introduce complexity to the material, they support cell invasion through the space between microgels, and they can be packed together to act as solids that can be easily extruded through a syringe.
Here, I will give examples of the design and use of granular hydrogels based on hyaluronic acid for use as injectable therapeutics, as well as in 3D printing. Microfluidic devices are used to fabricate the microgels using photoinitated thiol-ene reactions or radical polymerizations for intraparticle crosslinking where crosslinkers can be stable or responsive to local proteases. For cardiac therapeutics, we injected heterogeneous granular hydrogels into the myocardium and showed selective microgel degradation to release factors and introduce porosity for cellular ingrowth. In 3D printing, we jammed together microgels to form shear-thinning and self-healing hydrogels that could be printed either onto surfaces or within other hydrogels. These could be cell-laden or stabilized where necessary with secondary crosslinking. Most recently, we designed these granular hydrogels to be conductive, through an in situ metal reduction process of silver onto microgels and then jamming into solids with high conductivity due to increased surface area when compared to traditional hydrogels. The conductive granular hydrogels were shown to influence electrical tissue bridging in muscle defects and could be 3D printed into conductive lattices. Overall, the granular hydrogel design opens up new opportunities in the design of functional hydrogels in biomedical applications.
2:00 PM - *SB04.02.02
Hyaluronic Acid and Polypeptides Assemblies—New Designs, from Thin Coatings to Hydrogels with Antimicrobial Properties
Inserm / University of Strasbourg1Show Abstract
All implantable biomedical systems face several risks once in contact with the host tissue: excessive immune response to the implant and development of bacterial biofilms. A multifunctional surface coating that can address all these two issues concomitantly would significantly improve clinical outcomes. We hypothesized that polyarginine (PAR), a synthetic highly cationic polypeptide, can act on macrophages to control innate immune response because arginine is an important component of macrophage metabolism. Moreover, PAR is susceptible to act as an antimicrobial agent due to its positive charges. We developed a new polyelectrolyte multilayer film based on PAR and hyaluronic acid (HA). The layer-by-layer PAR/HA films have a strong inhibitory effect on the production of inflammatory cytokines released by human primary macrophages subpopulations . This could reduce potential chronic inflammatory reaction following implantation. Next, we show that PAR/HA films were very effective to inhibit Gram-positive and Gram-negative pathogenic bacteria associated with infections of medical devices  . We demonstrate that exclusively films constructed with poly(arginine) composed of 30 residues (PAR30) acquire a strong antimicrobial activity. Moreover, changing HA by another synthetic or natural polyanion did not provide any more antimicrobial activity. HA is a key component of the system and the mechanism behind this property has been elucidated. The cytocompatibility of the PAR/HA films was assessed with several cell types playing a major role in tissue regeneration. This system can also be fabricated in the form of hydrogel, useful to provide antibacterial properties to porous implants like surgical meshes. In this case, a precise controlled release can be achieved with strong efficiency over multi-infections. Recent developments to render these systems smart and responsive have also been made to obtain a release and activity only when bacteria are closed to the implants.
 Özçelik, H. et al. Adv. Healthc. Mater. 2015; 4, 2026-36.
 Mutschler, A. et al. Chem. Mater. 2016; 28, 8700-09.
 Mutschler A. et al. Chem. Matter., 2017; 29, 3195–01.
2:30 PM - SB04.02.03
In Vitro Hair Shaft Generation from 3D Cell Aggregate for Hair Regenerative Medicine
Rikuma Nakajima1,Akihiro Shimizu1,Tatsuto Kageyama1,2,Junji Fukuda1,2
Graduate School of Engineering, Yokohama National University1,Kanagawa Institute of Industrial Science and Technology (KISTEC)2Show Abstract
Hair loss is a common concern among numerous individuals. Hair regenerative medicine has recently been attracted attention as a promising treatment approach for hair loss. Hair follicle morphogenesis is triggered by interactions between epithelial and mesenchymal germ layers during embryogenesis, and various approaches for fabricating tissue grafts by recapitulating such interactions in vitro have been examined in the past decade. Since thousands of tissue grafts are necessary for a single patient, approaches for fabricating tissue grafts should be scalable. Herein, we fabricated a microwell array device with oxygen-permeable poly(dimethylsiloxane), wherein epithelial and mesenchymal cells spontaneously formed hair follicle germ (HFG)-like cell aggregates in 3 d of culture. This approach was scalable and >5,000 HFGs were prepared simultaneously by simply seeding the two types of cells and culturing them for 3 d in the device (T. Kageyama et al. Biomaterials, 154, 291-300, 2018). This approach is simple and robust. However, there are still certain issues, including further improvement of hair regeneration owing to the low hair regeneration efficiency when patients’ own cells are employed.
In this study, we propose an approach to screen HFGs based on their hair regeneration potential. HFGs generated herein produced hair shafts in vitro, which sprouted from the HFGs at 12 d of culture and reached ~200 µm in length at 23 d of culture. However, only less than 1% of HFGs (a few/300 HFGs) generated hair shafts. Thus, we optimized culture conditions and found that supplementation of an extracellular matrix hydrogel, Matrigel, significantly increased hair shaft generation. HFGs exposed to Matrigel generated hair shafts at 4 d of culture, which then ~1,400 µm in length at 17 d of culture. Moreover, the efficiency of regeneration was significantly increased (~90%, 275/300 HFGs). Scanning electron microscopy and transmission electron microscopy revealed that the hair shafts have typical morphological features including hair cortices, hair cuticles, melanosomes, and micro-fibrils. HFGs producing hair shafts at 6 d were selected and transplanted into the dorsal and scalp skin regions of nude mice. The hair generation efficiency was 85.4%, which was significantly greater than that of HFGs generated using our previous approach without pre-screening (i.e., 65.0%). The present approach may provide a better strategy for hair regenerative medicine.
2:45 PM - SB04.02.04
Zapping Bacterial Infection with a Fast Setting Biodegradable Hydrogel
Daniela Vieira1,Samuel Angel1,Edward Harvey1,Geraldine Merle1
McGill University1Show Abstract
Wound infections have been a major challenge especially for military medicine. As the care of casualties continues to enhance survival rates, infectious complications will remain a major cause of morbidity. When bacteria biofilm is formed at the wound site, the infection is significantly more difficult to treat, increasing the healing time and the cost of the treatment. Conventional way of treatment is surgical debridement combined with antibiotics to prevent the growth of bacteria in and around wound before infection is established. Because of the misuse and overuse of antibiotics more them 50% of the bacteria are resistant to standard antibiotics. Bacterial resistance has become a serious global problem with a morbidity up to 45% in developing countries. Additionally, antibiotics often have serious negative effects on normal bodily functions. Given these challenging concerns, new strategies to treat bacterial infection are necessary. The use of antimicrobial peptides, polysaccharides and other antimicrobial components are an alternative. However, they are also hemolytic, toxic and easy to lose efficacy. Using electrical current (EC) to break down and destroy bacterial biofilms has been investigated for several years. Our concept is based on targeting the bacteria synergistically on various fronts. The impact of EC associated with antibacterial materials may be more significant. In this work, we designed a bioresorbable hydrogel free of antibiotics able to combat antibiotic resistance and help heal infected wounds. We synthesized an injectable biodegradable hydrogel based on silk fibroin (SF) and silver nanoparticles (Ag-NP) capable of fast setting, transporting EC and killing bacteria. SF solution was prepared following Rockwood protocol. This biocompatible and biodegradable natural polymer contains some tyrosine motifs, which reduce silver ions (Ag+) into Ag-NP with great toxicity against diverse bacteria. Sequentially, AgNO3 was added, mixed and exposed 24 h to incandescent light at room temperature. SF hydrogel and Ag-NPs exhibit an excellent conductivity of 1.2 S cm-1, allowing the electrons to flow. Different conditions were performed to evaluate cytotoxicity and bacteria viability. Fist, as a control, just cell or bacteria (C/B). Second, C/B in contact with hydrogels (t= 60s). Third, C/B in contact with EC (1mA/60s). And finally, our approach, C/B in contact with the hydrogels combined with EC (1mA/60s). Hydrogels were removed right after from the medium. There is no toxicity on CHO mammalian cells treated with hydrogels or EC, separately or combined. In contrast to the effect in cells, the proposed work has a significant toxicity on E. Coli. Only hydrogels have no significant effect on bacterial killing, and further for EC, with 12.9% and 8.6% of death, respectively. However, the combined effect produced 77.8% of dead bacteria. In order to analyze these effects, Ag+ release, and ROS (oxygen species) generation was performed. Treatments with hydrogels and the combined effect presented similar Ag+ release, 21.94 ± 2.21 ppm and 19.59 ± 3.32 ppm, respectively. It is not the mainly cause of bacterial toxicity. However, for ROS generation, a difference of 50% was found between treatments, showing an interesting contribution of EC to produce ROS. Ag-NPs are able to generate of ROS, and combined with EC, its ability increased, being more efficient. Furthermore, bacteria require extracellular electron acceptors to realize electron transport in its respiratory chain. Thereby, we believe these hydrogels have an electron extraction ability. It means, it may form a circuit to electron transfer, causing an extraction of electron from the bacteria membranes. Eventually, it causes membrane disruption and, consequently, the bacterial death. These results are promising and unprecedented in literature.
3:30 PM - *SB04.02.05
Bioinspired Elastin-Based Adhesives for Surgical Glue Applications
Purdue University1Show Abstract
A successful biomedical adhesive must be biocompatible, set in a wet environment, match the mechanical properties of the surrounding tissue, and have proper adhesive and cohesive properties. Current technologies do not meet these needs. We developed bioinspired protein-based adhesives that combine adhesion from DOPA residues found in mussel adhesive proteins with the mechanical properties of elastin, which can also coacervate in response to the environment. We demonstrated that these proteins are cytocompatible, provide the strongest bonds of any rationally designed protein when used completely underwater, and can be easily applied underwater because they coacervate in physiological conditions. Recently, we investigated different formulations and crosslinking chemistries in physiologically relevant environments by using pig skin substrates and curing in a warm, humid environment.
4:00 PM - SB04.02.06
Bioinspired Self-Healing Protein Materials
Abdon Pena-Francesch1,Huihun Jung2,Melik Demirel2,Metin Sitti1
Max Planck Institute for Intelligent Systems1,The Pennsylvania State University2Show Abstract
Recent research efforts have focused on developing soft, flexible, compliant materials for medical robotics, biointerfacing, and biosensing applications, with properties matching those of biological tissue. Because of their intrinsic softness, these materials are susceptible to cut, puncture, scratch, and/or tear damage that compromises the physical integrity of the device/interface. Soft self-healing materials offer a solution to this challenge and improve the long-term reliability, although many of the commonly explored self-healing chemistries are not biocompatible and are time-consuming (long healing times). To overcome these problems, we present biocompatible synthetic protein-based materials, inspired in squid proteins, that self-repair microscopic and macroscopic damage within seconds. The self-healing mechanism relies on the formation of reversible physical crosslinks in an elastomeric protein network. The healing process takes place in physiological conditions and the mechanical properties are recovered after healing. Furthermore, the protein material can be functionalized with biomolecules such as enzymes that maintain their activity after several healing cycles. These protein-based self-healing materials find applications as adaptive actuators for soft robotics, dependable biosensing platforms, and protective textiles against chemical and biological warfare agents.
4:15 PM - SB04.02.09
pH Triggered Drug Release from Hydrogel Layers Integrated in Magnetically Controlled Microdevices
Roberto Bernasconi1,Bradley Nelson2,Salvador Panè2,Marinella Levi1,Filippo Rossi1,Luca Magagnin1
Politecnico di Milano1,ETH Zürich2Show Abstract
Two of the most crucial topics in modern medicine are medicines administration routes and their relative pharmacokinetics inside human body. The largest part of conventional drug delivery methodologies, like absorption through the gastrointestinal tract or intravenous injection, are generally based on the non-selective distribution of the active substance in the whole body, mediated by blood circulation. With these delivery methodologies, however, most of the drug reaches non-target parts of the body. This implies that higher dosages must be provided to reach the optimal concentration in the target organ, lowering administration efficacy and amplifying drug side-effects.
To overcome these problematics, advanced administration strategies based on targeted delivery have been recently developed . More specifically, drugs are released in controlled amounts only in correspondence of the target organ. This approach requires a superior temporal and spatial control over release, which is challenging to achieve. A possible solution to control drug delivery timing can be the use of stimuli responsive polymers , which can release therapeutic drugs under the influence of an external stimulus (thermal, chemical, …). By employing this class of advanced materials, medicines can be released upon request and with controlled rates. Conversely, to allow spatial control, a possible key can be the use of magnetically controlled microrobots . These microdevices are able to perform different tasks in-vivo, including for example cell transport  and medicine delivery applications . For the latter, they can be covered with drug releasing materials and wirelessly guided inside human body to perform administration only in close proximity of the target organ. Moreover, magnetic field is harmless for humans, allowing a limited invasivity of the microrobots in conjunction with a great manipulation precision.
In this context, we describe the realization of magnetically guidable microdevices integrating a hydrogel layer specifically tailored to perform pH triggered drug release. The microdevices are characterized by a microporous structure, which increases hydrogel loading capability and that is obtained employing additive manufacturing. More specifically, we employ microstereolithography, a highly scalable and flexible 3D printing technique able to yield micrometric sized objects at relatively low cost. To allow magnetic actuation, a CoNiP layer is applied by mean of wet metallization on the 3D printed devices. The same technique is employed also to deposit a gold layer to make the surface biocompatible. Finally, the micropores are filled with an alginate hydrogel modified with click chemistry, in which the drug is binded to the biopolymer chains by mean of a pH cleavable bond. In this way, release takes place only when the device reaches the part of the body presenting the correct pH range. An example of possible application may be drug release in well-defined zones of the gastrointestinal apparatus, which is characterized by different pH levels according to the tract considered .
 M.W. Tibbitt et al., J. Am. Chem. Soc. 138, 704-717 (2016)
 H.P. James, Acta Pharmaceutica Sinica B 4(2), 120-127 (2014)
 J.J. Abbott, IEEE Robot. Autom. Mag. 14, 92-103 (2007)
 R. Bernasconi et al., Mater. Horiz. 5, 699-707 (2018)
 S. Fusco, Adv. Healthcare Mater. 2(7), 1037-1044 (2013)
 D.F. Evans et al., Gut 29, 1025-1041 (1988)
4:30 PM - SB04.02.07
Piezoionics as a Mechanism for Sensing in Gels
John Madden2,Yuta Dobashi1,2,Yael Petel2,Dickson Yao2,Carl Michal2
University of Toronto1,University of British Columbia2Show Abstract
Hydrogels have been shown to be effective as transparent electrodes in pressure and touch sensors, forming “ionic skin”. Interestingly, the gels themselves also generate voltage when they are deformed. An ionic sensing effect has long been known in cartilage tissues in which counter ions that balance the charged collagen backbone are redistributed when pressure is applied. In this work, we propose a new mechanisms in which voltage arises from differential rates of ion motion within the gel when pressure gradients are applied. Fluid flow is generated within pores that are so small that ions experience additional drag. Some ions move more slowly than others, leading to voltage generation that is typically in the tens of millivolts.
In this work, we report on our investigation of pressure-induced ion redistribution and electric field generation arising due to differential cationic and anionic mobilities in solid polymer electrolytes. An organic phase solid polymer electrolyte was synthesized by a solution-casting technique using lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), propylene carbonate (PC) and Poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP). The PVDFHFP/PC/LiTFSI gels of varying concentrations (0.1 M ~ 3 M) were subjected to mechanoelectrical transduction tests and the magnitude of generated potentials were recorded. Subsequently, diffusion NMR (pulsed field gradient spin echo) was performed on the polymer electrolytes to determine the self diffusion coefficients of the lithium and TFSI ions. The results revealed that the signs of the voltages generated were largely determined by the ion of higher diffusivity. Subsequently, the mechanotransduction was numerically modelled by coupling Darcy’s flow velocity to the convective flux of the ions, and subsequently computing the Nernst Planck equation. The equation was modified such that for each transport coefficient (diffusion, convection, and electrophoretic), hindrance factors were imposed representing the slowing of each ionic species by the presence of the polymer matrix. The hindrance is relative to solvent flow through the pores in the case of convection, and relative to bulk solution in the case of diffusion. Using measured the ionic diffusion coefficients and the Darcian permeability as the inputs, and using the hindrance factors as fit parameters, the observed mechanotransduction effect is largely in agreement with measurements.
We further show that these sensors, which, like piezoelectrics, do not require any external power beyond the induced mechanical deformation, can readily be formed into sensor arrays. They produce sufficient voltage and current to stimulate nerve and muscle activation – a possible area of application.
SB04.03: Poster Session I: Hydrogel I
Marc In het Panhuis
Monday PM, December 02, 2019
Hynes, Level 1, Hall B
8:00 PM - SB04.03.01
Fabricating Tough and Elastic Photo-Actuating Hydrogel Fibres
Andrea Diaz-Gaxiola1,Sara Correia Carreira1,Adam Perriman1,Michael Dicker1
University of Bristol1Show Abstract
The application of hydrogels for the creation of soft machines can be challenging, given their traditionally limited range of mechanical properties . However, the last decade has seen great advances in the toughness and 3D printability of actuating hydrogels, but such systems have largely been limited to those stimulated by localised environmental changes in humidity, temperature or pH –. Conversely, light controlled systems offer unique properties including remote activation, wavelength selectivity and localised actuation. However, creating tough, printable photo-responsive hydrogels with appreciable actuation strain is still a significant challenge .
Our robust single fibre (15 cm long, 300 μm diameter) hydrogel actuators are manufactured using a biocompatible microfluidics spinning approach. The material comprises a photo-responsive chrysophenine doped polyurethane – polyacrylic acid interpenetrated hydrogel network (PU-AA IPN). The photo-active chrysophenine has a characteristic absorbance band from 460 to 490 nm (blue light), which triggers a trans-cis transition that disrupts the π stacked network. This, in turn, shifts local dielectric constant, displacing water from the polymer network, which gives rise to macroscopic actuation.
We demonstrate that by optimising the chrysophenine doping levels, the actuation strain can be increased to 17%. This is far in excess of analogous systems, e.g., 2-hydroxyethylmethacrylate, ethylene glycol-dimethacrylate co-polymers equilibrated in a 0.4% chrysophenine solution displayed photo-actuated strains of under 1% . Moreover, and regardless of the fibres’ cross-sectional area, the hydrogel could be stretched up to 4 times its initial length. In conclusion, we demonstrate the successful fabrication of single fibre photo-actuators which amplify the molecular interactions between chrysophenine and the tough PU-PAA IPN, achieving spatiotemporal independence and control.
 P. Calvert, “Hydrogels for Soft Machines,” Adv. Mater., vol. 21, no. 7, pp. 743–756, Feb. 2009.
 C. Lv et al., “Humidity-responsive actuation of programmable hydrogel microstructures based on 3D printing,” Sensors Actuators B Chem., vol. 259, pp. 736–744, Apr. 2018.
 S. E. Bakarich, R. Gorkin, M. in het Panhuis, and G. M. Spinks, “4D Printing with Mechanically Robust, Thermally Actuating Hydrogels,” Macromol. Rapid Commun., vol. 36, no. 12, pp. 1211–1217, Jun. 2015.
 Y. Zhang, J. Liao, T. Wang, W. Sun, and Z. Tong, “Polyampholyte Hydrogels with pH Modulated Shape Memory and Spontaneous Actuation,” Adv. Funct. Mater., vol. 28, no. 18, p. 1707245, May 2018.
 Y. Hu, Z. Li, T. Lan, and W. Chen, “Photoactuators for Direct Optical-to-Mechanical Energy Conversion: From Nanocomponent Assembly to Macroscopic Deformation,” Adv. Mater., vol. 28, no. 47, pp. 10548–10556, Dec. 2016.
 G. Van Der Veen; W. Prins, “Photomechanical Energy Conversion in a Polymer Membrane,” Nat. Physycal Sci., vol. 230, no. March 15, pp. 70–72, 1971.
8:00 PM - SB04.03.02
Double Covalent Network—3D Printing of Customized, Complex Hydrogel with Hyper-Elastic, Self-Adhesive and Shape Memory Effect
Northeastern University1Show Abstract
Double covalent network hydrogels have attracted extensive attention as an innovative material having both high-water content and extremely high mechanical strength. 3D printing has revolutionized the way products are developed and customized, as satisfied with the integration of the complex structure and multiple-functions. Here, based on the classical PAMPS/PAAm double network strategy, a new 3D printing method, combined with nanocomposites enhancing mechanism and self-polymerized dopamine modification, is presented for customizing the complex double covalent network architectures.
Double network gels are characterized by a special network structure consisting of two types of polymer components with opposite physical natures: the first component is abundantly cross-linked polyelectrolytes (rigid skeleton) and the second component comprises of poorly cross-linked neutral polymers (ductile substance). The synthesis orders and process are vital to realizing their excellent mechanical performances which comparable to that of rubbers and soft load-bearing bio-tissues. However, tough mechanical feature and the unique crosslinking process make double network gel interesting and challenging on the developing in customization of 3D architectures.
Thus, this work reported a simple yet versatile method for establishing a fair balance between the dopamine polymerization and second covalent crosslinking network together with the doped-nanoparticles, which makes the double covalent network hydrogel into the customized, complex 3D architecture with hyper-elastic, self-adhesive, fatigue resistance and shape memory effect. This strategy could potentially expand double network gel’ application in fashion, medical devices, human tissue replacement and engineering.
8:00 PM - SB04.03.03
Synthesis, Characterization and Antimicrobial Measurement of BSA Conjugated Silver Nanoparticle Filled Hydrogel Nanocomposite
Olufolasade Atoyebi1,Berhanu Zewde1,Ayele Gugssaa1,Dharmaraj Raghavan1
Howard University1Show Abstract
Nanocomposite hydrogels is attracting significant interest due to their potential use in implants, drug delivery systems, and tissue design scaffolds. This paper reports about the synthesis of precursors (tetrazine-modified polyethylene glycol and norbornene-modified hyaluronic acid) to form crosslinked hydrogels and hydrogel nanocomposite. Click chemistry of precursors in combination with in situ encapsulation of preformed Bovine Serum Albumin (BSA) conjugated silver nanoparticles (Ag/BSA) yielded nanocomposite hydrogel. 1H-NMR of norbornene-modified hyaluronic acid and tetrazine-modified polyethylene glycol showed characteristic peaks for the vinylic protons of the endo and exo configuration of norbornene and tetrazine unit as well as PEG chains of tetrazine-modified polyethylene glycol, respectively. The Ag/BSA nanoparticles in the nanocomposite, were well dispersed as revealed by SEM and TEM, and were 20-30 nm in size. By TGA analysis, the percent of silver in the nanocomposite was established to be 2%. The interaction between the nanoparticles and the hydrogel was demonstrated by studying the shift in OH peaks of hydrogel via FTIR, changes in binding energy of O1s peak in XPS and measuring the desorption of nanoparticles from the hydrogel nanocomposites of various crosslinked system by AAS. Unlike native hydrogel, the hydrogel nanocomposite showed good antibacterial activity against gram positive/gram negative bactericides, and the loading of nanoparticles had a strong bearing on the extent of anti-bacterial activity.
8:00 PM - SB04.03.04
Self-Restorable Adhesive Hydrogels Synthesized Using Poly(N-vinylpyrrolidone) and Tannic Acid via Supramolecular Assembly
Myeong-gyun Nam1,Hyeon-Gyun Nam2,Ji-heung Kim1,Piljin Yoo1
Sungkyunkwan University1,Korea Advanced Institute of Science and Technology2Show Abstract
Supramolecular assembly and complexation is a powerful method to impart new functionalities to various organic compounds and is extensively used in biomedical, energy, and surface coating applications. Especially, when strong molecular interactions are exerted simultaneously, interacting molecules suffer the gelation by internal cohesive bonding, triggering a pseudo-crosslinking effect forming a supramolecular gel. Among various substances inducing supramolecular assembly, phenolic substances, e.g. 3,4-dihydroxy-L-phenylalanine (DOPA), are tremendously applied for adhesive materials owing to abundant hydroxyl groups driving supramolecular assembly via hydrogen bonding. However, in spite of the strong adhesive property of monomeric phenol, it is deficient to induce cohesive strength, resulting in rarely forming a supramolecular gel to secure its mechanical properties. Herein, to overcome this drawback, we realized a supramolecular coacervate hydrogel through simple mixing process of poly(N-vinylpyrrolidone) (PVP) and tannic acid (TA), resulting in internal cohesive interactions by virtue of the large molecular size of TA compared to monomeric phenols and enhanced molecular interactions triggered by a tremendous number of galloyl groups with a high density. Additionally, we tried to analyze the rheological and adhesive properties of PVP-TA coacervate hydrogels. Interestingly, on various substrates, remarkably high adhesive property is shown by PVP-TA hydrogel with abnormal self-healing property against extreme deformation. In detail, average adhesion strength of PVP-TA hydrogel shows 3.71 MPa on a glass substrate, which is 4 – 5 times stronger than that of conventional PVP.
8:00 PM - SB04.03.05
A Novel Self-Healing Hydrogel with Stretchable, Conductive and Super-Adhesion
Yimeng Wang1,Jing Peng1,Maolin Zhai1
Peking University1Show Abstract
Multifunctional and adhesive hydrogels show excellent potential for multifarious applications, such as tissue adhesives, sealants, and implantable electronic devices, but most of them still suffer from poor reusable performance, high synthesis complexity, and low conductivity when facing to electronic device adhesives. Herein, based on a fully physical crosslinking network, a novel self-healing hydrogel (named GOxSPNB) with various ratios of graphene oxide (GO) to soluble starch and poly(sodium 4-vinyl-benzenesulfonate-co-N-(2-(methacryloyloxy)ethyl)-N,N-dimethylbutan-1-aminium bromide) (P(NaSS-co-MOBAB) was synthesized successfully by a simple one-pot γ-ray radiation-induced polymerization. Due to the multi-physical crosslinking network inside the hydrogels among GO, starch and P(NaSS-co-MOBAB) polymer, such as electrostatic interactions and hydrogen bonds, the resultant nanocomposite hydrogels exhibit fast automatic self-healing ability. In the meantime, the obtained hydrogels show super stretchable ability, non-toxicity, and ionic conductivity about 10.5 mS dm-1. With high adhesive components such as soluble starch and acrylate derivatives inside, it was also endowed with super adhesion to various substrates, including solid materials and biological tissues. For example, the adhesion strength to the copper plates was about 60.5 MPa at room temperature, nearly one magnitude larger than other reversible adhesives that have been reported. Considering the facile preparation and all the advanced properties, the procedure provided here opens up a promising avenue to develop multifunctional hydrogel glues for design and fabrication of smart electronic device adhesives.
8:00 PM - SB04.03.06
Design of Tunable Multicolor Fluorescent Materials as Strain Sensors
Dong Zhang1,Jie Zheng1,Yanxian Zhang1,Yonglan Liu1,Shaowen Xie1,Li Tang1
The University of Akron1Show Abstract
Development of tunable multicolor fluorescent materials is important but challenging for fundamental research and practical applications. In this work, a series of trichromic (blue, green, and red), fluorescent polymers are synthesized by covalently copolymerizing spiropyran-based, naphthalimide-based, and pyrene-based monomer onto hydrophilic poly(acrylic acid-co-acrylamide) chains separately. Due to the dynamic fluorescence resonance energy transfer process between electron donors and acceptors, the tunable rainbow-color fluorescent polymer films and polymer solutions can be effectively fabricated by simply mixing and blending monochrome copolymers. Interestingly, utilizing the abundant carboxyl groups in the macromolecular chains, the thin fluorescent polymer films can also form physical hydrogels in a single step through carboxyl-Zn2+ coordination. Furthermore, such dynamic physical cross-linked hydrogels could also be easily loaded onto complex electric driven devices, achieving organic combination of fluorescent hydrogels and actuators based on reversible sol-gel transition. Ultimately, we demonstrated a new strategy to enhance mechanical properties by embedding this mechanically weak fluorescent gel into a brittle alginate hydrogel shell via metal ion (Zn2+ ion) diffusion induction mechanisms. We believe that our design principles and the resultant multicolor materials will broaden the design of next-generation fluorescent materials.
8:00 PM - SB04.03.07
Stimuli Responsive Shape Recovery Hyaluronic Acid Hydrogel Using Ice-Template
Eunsook Park1,Haeshin Lee1
Korea Advanced Institute of Science and Technology1Show Abstract
Hyaluronic acid (HA), an essential component of the extracellular matrix, has been recognized as a promising building block in cell therapy and tissue engineering due to its excellent biocompatibility and biological properties. Furthermore, HA is versatile in functionalization with various crosslink-moieties and has been easily transformed into hydrogel via chemical and physical crosslinking for cell culture and transplantation. However, cross-linker and photoinitiator, used in the crosslinking reaction, cause chemical and radical induced cytotoxicity. Current catechol modified hyaluronic acid (HA-C) was reported as a novel candidate that overcame these limitation, showing low cytotoxicity and tissue adhesive properties. However, it was inevitable to use a high pH environment or oxidizing agent due to slow catechol oxidation rate. Moreover, the gel had low mechanical properties and was unable to maintain its shape.
In the study, we describe another technique to make mechanically robust HA-C gel using the ice template. When HA-C is frozen, the formation of ice promotes the oxidation of catechol by two mechanism; 1) the increase of the local concentration of HA-C in the unfrozen area, and 2) the increase of buffer pH with decreasing temperature. Initially, an injectable gel is formed but as freezing and thawing cycle are repeated, a solid-like free-standing gel is formed. When compressed, the water trapped in the pore squeezes out and the gels show compressibility due to large porous structure that is prepared by ice. However, when water feeding, the gel present rapid water uptake properties and repeatable water induced shape recovery. In addition to, the large pore structure of the gels improved the permeability of nutrients and cells and biocompatibility. These gels is best mimic bio-tissues (e.g. cartilage) with compressible properties and porous structure, and thus can be used promising building blocks in tissue engineering.
8:00 PM - SB04.03.08
The Biocompatible Hydrogel Skin for Long-Term Used Catheter
Yueying Yang1,Yan Yu1,Qing Ling1,Jiaxin Wang1,Le Lin1,Jianfeng Zang1,Xuanhe Zhao2
Huazhong University of Science and Technology1,Massachusetts Institute of Technology2Show Abstract
With the rapid development of global science and technology, the average life expectancy of human beings is generally extended, and the social problems caused by the aging of population are also increasing. Due to the rapid increase of diseases caused by aging, such as heart disease, high blood pressure, stroke, etc, the number of hospitalized patients increases rapidly, and the number of bedridden patients also increases continuously, accounting for 30% of hospitalized patients. The catheters used by bedridden patients for long periods of time need to be replaced on average once a week, however it greatly increases the risk of urinary tract infections. The existing catheters made of natural rubber, silicone rubber or PVC, which has high friction coefficient, render patients uncomfortable. Since the external environment is connected with the human body through the catheter, the risk of patients’ infection is increased. In our study, we coat the hydrogel skins on inner and outer surfaces of the Catheter, the hydrogel skins exhibit tissue-like softness and provide superior low-friction, antifouling, anti-bacterial, to the catheter. In addition, we demonstrate the new catheter’s features through animal experiment.
8:00 PM - SB04.03.09
Fabrication of Photo-Curable Polyurethane-Acrylate for 3D Printing Based on Viscosity and UV Curing Time
PilHo Huh1,WonBin Lim1
Pusan National University1Show Abstract
Nowadays, 3D printers have been undergone much attention in all fields of industry. The photo-curing resins which ranging from rigid to flexible, are successfully prepared using the synthesis of Polyurethane-Acrylate. It will be used for according to the application through the measurement of flexural strength and hardness. The intrinsic viscosity of the photo-curable monomer and polymer is measured to target the molecular weight of the material. The photo-curing polymer is produced through physical or chemical reaction, and the curing time and physical properties of the material are adjusted according to the purpose. It can be controlled the ratio of the photo initiator and polymer. For example, Thermoplastic polyurethane (TPU) series based on polyethylene glycol(PEG) as a polyol and hexamethylene diisocyanate (HDI) as a isocyanate were synthesized as a function of molecular weight formulation. After that, PU-acryl will be synthesized by attaching hydroxyethyl-methacrylate(HEMA) and used for DLP 3D printing by controlling the content ratio of photo-initiator and addition multifunctional acrylate.
8:00 PM - SB04.03.10
3D-Printed Microbe and Consortia Hydrogels for on Demand Bioproduction and Preservation
Trevor Johnston1,Shuo-Fu Yuan2,James Wagner2,Xiunan Yi2,Abhijit Saha1,Alshakim Nelson1,Hal Alper2
University of Washington1,The University of Texas at Austin2Show Abstract
Living materials are composites of polymers and living cells wherein the function of the material is derived from the residing cells. Here, we describe a 3D-printed hydrogel-based system for harnessing the bioactivity of embedded microbes for on-demand small molecule and peptide production in mono-culture and microbial consortia systems. This platform bypasses the challenges of multi-organism consortia by spatially organizing organisms into hydrogel inks to precisely control the final consortium composition and dynamics without the need for synthetic control. Furthermore, we demonstrate that these hydrogels provide protection from preservation techniques (including lyophilization) and can sustain active metabolic function for over 1 year of repeated use. We demonstrate the utility of this approach (compared to traditional liquid-based culturing) for four chemicals and peptide antibiotics using through both mono-cultures and cross-feeding and parallel consortia of yeast and E. coli. In all cases, the printed hydrogel ink’s efficiency in repeated production phases, both pre- and post-preservation, outperformed liquid culture. We envision this technology being a step forward in the ease of use of complex designed biological systems for the expanded, on-demand production of a variety of high-value compounds.
8:00 PM - SB04.03.11
A Supramolecular Hydrogel for Spatial-Temporal Release of Auxin to Promote Plant Root Growth
Nankai University1Show Abstract
So far, synthetic auxins other than indole-3-acetic acid (IAA) have been widely used in both scientific studies and agricultural and horticultural practices. The synthetic auxin 1-naphthalene acetic acid (NAA) is popular because of its relative stability and its lipophilicity, which allows it to freely enter the plant cell. However, because of the rapid diffusion of NAA in agarose hydrogel, the most commonly used technique for physically encapsulating NAA in an agarose hydrogel or hydrogel beads cannot fulfil the need for the spatial release of NAA for plant research. It remains a challenge to develop materials for the spatial-temporal release of auxin for research use.
In this study, we demonstrated the effectiveness of an auxin-based hydrogelator linked by a hydrolysable ester bond. Hydrogel I, formed by the gelator (NAA-G’FFY) linked with an ester bond, was able to release 1-naphthaleneacetic acid (NAA), whereas hydrogel II, formed by the gelator without an ester bond (NAA-GFFY), was not. By mixing NAA-G’FFY with Fmoc-GFFY to form a two-component hydrogel, the spatial and temporal release of NAA was achieved, promoting on-site auxin responses including primary root elongation and lateral root formation in the model plant Arabidopsis thaliana. The strategy of using a hydrolysable ester bond to connect drug molecules and self-assembling peptides could lead to the development of supramolecular hydrogels with more controllable drug release profiles.
In summary, we demonstrated that an auxin-based supramolecular hydrogel connected by a hydrolysable ester bond has a good capacity to slowly release NAA into the environment, while the control connected by an amide bond cannot release NAA. The spatial and temporal release of NAA could be a useful new tool in the study of auxin-induced plant growth and development.
8:00 PM - SB04.03.12
β-Galactosidase Instructed Supramolecular Hydrogelation for Selective Identification and Removal of Senescent Cells
Nankai University1Show Abstract
Cellular senescence is a natural process to prevent the proliferation of damaged or stressed cells, and it is also believed to be beneficial in wound healing. However, senescent cells tend to accumulate upon persistent damage or during aging, which impairs tissue functions and accelerates aging. Recent studies indicate that the clearance of senescent cells can delay features of aging and counteract the loss of tissue hemeostasis after chemotherapy or chronic damage. It is therefore very important to develop strategies for selective identification and removal of senescent cells.
In this work, we introduced a novel strategy of β-galactosidase (β-Gal) instructed peptide self-assembly to selectively form nanofibers and hydrogels in senescent cells. We demonstrated that the in situ formed nanofibers could alleviate endothelial cell senescence by reducing P53, P21, and P16INK4a expression levels. We also demonstrated that our strategy could selectively remove senescent endothelial cells by inducing cell apoptosis, with an increase in the BAX/BCL-2 ratio and caspase-3 expression. Our study reports the first example of enzyme instructed self-assembly (EISA) by a sugar hydrolase, which may lead to the development of supramolecular nanomaterials for the diagnosis and treatment of many diseases, such as cancer, and for other applications, such as wound healing and senescence.
As a result, this is the first example of supramolecular hydrogel formation triggered by a sugar hydrolase. Sugar hydrolases play important roles in many diseases, and we envision great promise for the diagnosis and treatment of these diseases by sugar hydrolase-controlled supramolecular nanomaterials.
8:00 PM - SB04.03.13
Supramolecular Nanofibers of Drug-Peptide Amphiphile and Affibody Abolish HER2+ Tumor Growth
Nankai University1Show Abstract
Antibody-based medicines and nanomedicines are very promising for cancer therapy due to the high specificity and efficacy of antibodies. However, antibody-drug conjugates (ADCs) and antibody-modified nanomaterials frequently suffer from low drug loading and loss of functions due to the covalent modification of the antibody.
We herein reported on a novel and versatile strategy to prepare supramolecular nanomaterials by the co-assembly of an affibody (antiHER2) and drug-peptide amphiphiles. During the enzyme-instructed self-assembly (EISA) process, the drug-peptide amphiphile could co-assemble with the affibody, resulting in supramolecular nanofibers in hydrogels. The drug loading in the supramolecular nanofibers was high (>30 wt%), and the stability of antiHER2 was significantly improved in the nanofibers at 37 °C (>15 days in vitro). The supramolecular nanofibers exhibited high affinity for HER2+ cancer cells and could be efficiently taken up by these cells. In a mouse tumor model, our supramolecular nanofibers abolished HER2+ NCI-N87 tumor growth due to the good accumulation and retention of nanofibers in tumor.
We demonstrated a novel and versatile method to prepare nanomedicines composed of drug-peptide amphiphiles and antibodies/affibodies by the EISA process. Compared with general ADCs that had very low drug loading, our system possessed much higher drug loading (31.6 and 30.2 wt% of CRB in co-assembled nanofibers with 10 and 15 wt% of affibody). The stability of the affibody could be significantly improved in our supramolecular nanofibers. More importantly, the in vitro and in vivo results indicated the excellent performance of our supramolecular nanomedicines, which possessed good targeting and therapeutic effects for cancer diagnostics and therapy. We also envision the generation of more supramolecular nanomedicines for the diagnostics and treatment of important diseases.
8:00 PM - SB04.03.14
Spiral-Shaped Stimuli-Responsive Hydrogel Actuator for Controlling Compression and Expansion
Koki Yoshida1,Hiroaki Onoe1
Keio University1Show Abstract
Stimuli-responsive hydrogels swell and shrink corresponding to external stimuli such as temperature, pH, light, and chemical compounds. These characteristics are attractive for soft actuators including artificial muscles, biomimetic robotics, and microfluidic components. Current challenges of hydrogel actuators are controlling their displacement and deformation direction, since bulk stimuli-responsive hydrogels only swell/shrink isotropically, as determined by the nature of the hydrogel materials. To overcome this challenge, various types of double-layered hydrogel actuator have been developed to controlling deformation direction, however controlling displacement of the stimuli-responsive hydrogel materials has not been achieved.
Here we present spiral-shaped stimuli-responsive hydrogel actuator for controlling deformation direction (compression/expansion). The magnification of deformation and controlling the deformation direction by shrink/swell characteristics can be enhanced just by the shape of spirals without any molecular modification of materials.
Simulation of actuation of the spiral-shaped actuator:
We use finite element simulation (COMSOL) for simulating the actuation of the spiral-shaped actuator. We consider the spiral-actuator with a diameter of gel Dgel = 300 µm and a diameter of spring Dspring = 1000 µm. We apply a shrinkage ration of stimuli-responsive hydrogel α = 0.6 which determined by measuring a shrinking ration of the stimuli-responsive hydrogel. The Double-layered spiral-shaped actuator behaved as axial compression with winding up. In contrast, when patterned stimuli-responsive hydrogel in the outside of spiral-shaped actuator, spiral-shaped actuator behaved as an axial expansion with winding down.
Fabrication of spiral-shaped stimuli-responsive hydrogel actuator:
We prepared a bevel-tip capillary by cutting a perfluoroalkoxy (PFA) microtube (inner diameter: 200 μm) at the tip angle to ~20°. The tube was set horizontally to the liquid surface. By using bevel-tip capillary, a continuous flow of mixed sodium alginate and poly(N-isopropylacrylamide-co-acrylicacid) pre-gel solution was extruded in CaCl2 solution, resulting in spontaneous formation a spiral-shaped hydrogel with a wide range of gradient pitches via buoyancy force. We used double-layer laminar flow for the formation of double-layered spiral-shaped hydrogel composed of stimuli-responsive part and non-responsive part. The resulting spiral-shaped hydrogel has double-layered structures and different pitches.
Results of spiral-shaped actuation:
We applied stimuli to the spiral-shaped actuators in CaCl2 solution by heating at 50°C. The double-layered spiral actuator shrank with large compression. The double-layered spiral actuator was mainly compressed in an axial direction. These results indicate that the spiral structure enhances the magnification of shrinkage of stimuli-responsive hydrogels. Furthermore, expansion of a spiral actuator in the axial direction was achieved by using a double-layered spiral actuator whose boundary between the two layers was parallel to the axial direction of the spiral (outside: stimuli-responsive hydrogel). These results showed that shrinkage of the stimuli-responsive hydrogel was converted to large expansion movement in the axial direction. Therefore, these results indicated that the deformation direction can be controlled by patterning the stimuli-responsive hydrogel.
Conclusion: Compression and expansion motions of spiral-shaped actuator were magnified by forming a spiral shape, which was corresponding to the simulation results. Therefore, it is expected that various multiple complex actuation could be realized by other complex compartmentalization and encapsulating functional materials. The success of multiple complex movements and magnifying the deformation would open new avenues to various microscale biochemical applications such as autonomous soft robots and drug release systems.
8:00 PM - SB04.03.15
Alendronate-Functionalized Poly(2-oxazoline)s with Tunable Affinity for Calcium Cations
Maria Sanchez Fernandez1,2
Radboudumc1,Radboud University2Show Abstract
A library of poly(2-oxazoline)s functionalized with controllable amounts of alendronate, hydroxyl and carboxylic acid side groups was successfully synthesized to create novel polymers with tunable affinity for calcium cations. The affinity of alendronate-containing polymers for calcium cations was quantified using isothermal titration calorimetry. Thermodynamic measurements revealed that the Ca2+ binding affinity of these polymers increased linearly with the amount of alendronate functionalization, up to values (KCa2+ = 2.4 x 105 M-1) that were about 120-fold higher than those for previously reported polymers. The calcium-binding capacity of alendronate-functionalized poly(2-oxazoline)s was exploited to form robust hydrogel networks cross-linked using reversible physical bonds. Oscillatory rheology showed that these hydrogels recovered more than 100% of their initial storage modulus after severe network destruction. The versatile synthesis of alendronate-functionalized polymers and their strong and tunable affinity for calcium cations render these polymers promising candidates for various biomedical applications.
Marc In het Panhuis, University of Wollongong
Namita Choudhury, RMIT University
Ferenc Horkay, National Institutes of Health
Jurgen Groll, University of Wurzburg
SB04.04/SB01.04: Joint Session: 3D/4D Printing of Stimuli-Sensitive Materials
Marc In het Panhuis
Tuesday AM, December 03, 2019
Hynes, Level 3, Ballroom A
8:00 AM - SB04.04.01/SB01.04.01
Gels for Bioprinting—Finding, Functionalising, Formulating, Printing and Characterising
University of Wollongong1Show Abstract
The ability to create 3D printed structures containing living cells is providing a route to the creation of "living" systems that might be useful for bench top drug testing or implantables that facilitate tissue regeneration.
However, the realisation of a useful printed structure based on hydrogels is not a simple task. While we can build on the extensive knowledge that has accrued through cell-gel interaction studies to date, there are a number of dimensions that add to the challenge.
Central to these is that the gel containing the cells must undergo a reasonably rapid phase transformation. In addition, with some applications multiple cells and other bioactive entities need to be strategically distributed in 3 dimensions. Sterilisation of the components and/or the final structure is also of critical importance and finally knowing what we have created without destroying it remains a challenge.
Returning to the start of this process we encounter perhaps the most neglected aspect - most of the emerging hydrogels finding use in bioprinting are naturally occurring. So where do we find them - how do we ensure a reliable high quality source?
8:30 AM - SB04.04.02/SB01.04.02
Novel Hybrid Approach to 3D-Print Graphene/Polymer Composites
Tianhao Chen1,Xuechen Shen1,Taylor Morrison1,Hani Naguib1
University of Toronto1Show Abstract
Current 3D printing uses a wide range of plastic, metal, and ceramic materials, with no significant effort to integrate these techniques for multi-material fabrication. We previously developed a novel method to deposit non-viscous ink through a stable continuous jet formed by gearing-enhanced peristaltic pumping. This ink deposition technique was used to deposit graphene oxide (GO) ink in a binder jetting (BJ) process to fabricate GO/polyvinyl alcohol composites. In this technique, ink particles are accelerated to speeds of 2-10ms-1 to overcome surface tension forces tending towards pendant drop formation. Gearing is applied to achieve mechanical advantage (MA)<1, enabling high pump velocity. Motor acceleration made up for the lost torque. In recognizing that gearing could be used to increase torque with MA>1, we realized the potential to perform Direct Ink Writing (DIW) using our ink deposition system. To this end, we DIW-printed viscous graphene/nanocellulose inks. We also recognized that DIW and BJ shared similar layer change, material transport, and gantry motions, allowing the 2 techniques to be implemented in the same system. We designed and built the hybrid 3D printer, implementing transmission to switch gearing ratios. The hybrid printer was demonstrated to print Graphene/polymer composites using both DIW and BJ printing modes.
8:45 AM - SB04.04.03/SB01.04.03
Three-Dimensional Printing with Silica Cages
Jen-Yu Huang1,Tangi Aubert1,2,Ulrich Wiesner1,Tobias Hanrath1
Cornell University1,Ghent University2Show Abstract
Material scientists have now developed an extensive library of nano-sized building blocks, offering a vast panel of properties (optic, magnetic, plasmonic, catalytic, etc.). Nevertheless, combining these building blocks for the realization of multifunctional materials while controlling their structure from the nano- to the micro- and all the way to the macroscale still remains an open challenge in order to fully exploit their potential. In parallel, new material processing techniques such as 3D printing technologies are emerging for the fabrication of macroscopic highly engineered parts and devices. In this work, newly discovered silica nanocages are combined with digital light processing 3D printing technique for the rapid fabrication of mesoporous parts with arbitrary shapes and tunable internal structures. Complementary strategies are then deployed for the implementation and deliberate positioning of various functionalities throughout 3D printed objects with high control on the microstructure and macroscopic architecture of the superstructures. This approach paves the road for innovative device concepts and designs, that will benefit from the unique properties of nanomaterials and from the micro- and macroscale manufacturing capability of 3D printers.
9:00 AM - SB04.04.04/SB01.04.04
Magnetically Navigable 3D Printed Multifunctional Microdevices for Water Quality Control
Roberto Bernasconi1,Elena Carrara1,Marcus Hoop2,Fajer Mushtaq2,Bradley Nelson2,Salvador Panè2,Caterina Credi1,Marinella Levi1,Luca Magagnin1
Politecnico di Milano1,ETH Zürich2Show Abstract
Water contamination, either chemical or biological, is one of the main problems for public healthcare in many parts of the world. Contaminated water is a source of a great number of diseases caused by pathogens or by chemical agents. Many techniques are available to improve water quality, but in many cases these methods are not entirely environmentally friendly. Current research efforts are directed toward the use of harmless substances and safer methods. From the pathogens control point of view, silver is one of the most used non-antibiotic agents. Regarding chemical pollutants elimination, one of the most promising techniques is photodegradation mediated by titania (TiO2). This material photocatalytically generates reactive radicals able to oxidize pollutants upon exposure to an electromagnetic radiation. Functional layers of silver and titania can therefore be used to provide efficient water remediation.
An interesting approach consists in manufacturing multifunctional materials that exhibit both antimicrobial and photocatalytic activities. A fabrication technique able to yield this type of materials is electrolytic codeposition of particles with metals or alloys . For example, thanks to this wet deposition technique, a matrix of silver with embedded titania particles can be easily obtained. The final composite layer exhibits both antibacterial and photoactive properties. Water cleaning possibilities can be further expanded if the antibacterial and the photodegradation action is performed by microdevices covered with silver/titania composites. An example of such devices are the so-called microrobots , which can be wirelessly guided using magnetic field and placed exactly where the water decontamination action is needed. Examples of microrobots presenting photocatalytic  or antimicrobial activity  are available in literature, but none of them combines these two actions on the same device.
The aim of this work is the realization of cylindrical shaped microrobots combining biokilling and photodegradation thank to the presence of a bifunctional composite on their surface. Such microrobots are produced using 3D printing, more specifically microstereolithography, and are subsequently metallized using wet techniques. Two functional layers are applied on the surface of the 3D printed device: a CoNiP magnetic alloy and an Ag/TiO2 composite. The first makes possible the movement of the device under the influence of an external magnetic field, while the latter imparts the biocidal/catalytic activity to the device. We demonstrate that these devices exhibit antimicrobial activity toward methicillin resistant Staphylococcus aureus bacteria. Moreover, from the pollutants removal point of view, we prove that they can efficiently photodegradate a model molecule like rhodamine B when exposed to ultraviolet radiation.
 M. Musiani, Electrochim. Acta 45(20), 3397-3402 (2000)
 Nelson et al., Springer Handbook of Robotics, pp. 411-450 (2008)
 Musthaq et al., Adv. Funct. Materials 26(38), 6995-7002 (2016)
 Hoop et al., Adv. Funct. Materials 26(7), 1063-1069 (2016)
9:15 AM - SB04.04.05/SB01.04.05
Macroscale Double Networks—A Universal Method for Improving the Strength and Toughness of Soft Materials
Daniel King1,Tsuyoshi Okumura1,Riku Takahashi1,Jian Ping Gong1
Hokkaido University1Show Abstract
The double network concept has been revolutionary in its ability to turn soft, brittle hydrogels into tough, robust materials with mechanical properties that match the best synthetic elastomers. Double network hydrogels consist of two interpenetrating networks, where each network has a specific mechanical response: the “first network” acts as a sacrificial network, consisting of a rigid, extended network, and the “second network” is a globally percolated, stretchable network. When a double network hydrogel is stretched, covalent bonds of the first network break, dissipating energy; this process continues with increasing strain, until the sacrificial network is completely broken and the second network ruptures. The goal of this research is to demonstrate that the “sacrificial bond concept” is applicable at length-scales beyond the molecular scale. We aim to incorporate this design concept universally for application in structural and medical devices.
Like double network hydrogels, our system consists of a rigid “first network,” 3d printed polyurethane/polyacrylate grids, embedded in a soft and stretchable “second network,” silicone rubber. We found that when the strength of the matrix exceeds the strength of the grid, local fracture occurs in the grid, and stretching is isolated to the rubber in the fractured region. As stretching increases, the force increases, and when the local force exceeds the global strength of the grid, fracture will occur elsewhere in the composite. This process continues sequentially throughout the sample until all grid fracture sites are exhausted, and the matrix ruptures. By tuning the stiffness of the grid, we can independently control the yield strength and fracture strain of the composite, until a point where the grid strength exceeds the matrix strength, and the multiple fracture process no longer occurs.
We also systematically studied the interfacial interactions between the matrix and the reinforcing grid. Both interfacial adhesion as well as topological interlocking are important towards developing a robust composite. By adhesive interactions alone, only minimal fracture of the reinforcing phase occurs; topological interlocking is required to maximize fracture. Based on this result, we systematically change the grid size to modify the number of fracture events. In the optimized form, an increase in work of extension of ~50% over the neat matrix was achieved, representing a ~70% toughening efficiency versus the calculated maximum toughness. These results demonstrate that macroscale double networks can dramatically increase the toughness of soft materials.
9:30 AM - SB04.04.06/SB01.04.06
4D Printing Thermoplastic Polyurethane Hydrogel-Elastomer Trilayers for Structural Applications
University of Bristol1Show Abstract
Hydrogels represent a class of engineering materials that have great promise for integration within the human body; particularly by optimising and functionally grading their biophysical and biochemical properties. The ability to construct complex architectures through 3D printing is now common place but introducing the ability to transform a planar architecture into a new configuration once manufactured opens up the potential to minimise manufacturing complexity but maximising the design potential. This presentation will detail our latest design thinking utilising a multifunctional materials design methodology and 4D printing research for producing a diverse range of complex architectures utilising thermoplastic and hydrogel trilayer constructs. This unique methodology permits the viable construction of dynamically robust and complex bilayer and trilayer origami architectures for a new generation of active structures. In our study the resulting creations transform from flat 2D parts to 3D structures through submersion in water and return to their original configuration through dehydration. This technique uses commercially available materials and printers to enable a controlled and predictable actuation method that is more accessible and affordable than previous examples of hydration triggered 4D printing. We show the ability to create tessellated origami patterns, such as the Miura-ori origami fold pattern and the waterbomb configuration; the latter being a design that has not previously been realised with 4D printing. These new designs demonstrate how the integration of multiple trilayers into a single 3D print enables through-thickness control of actuation resulting in the formation of active structures with complexity beyond what has previously been achieved with 4D printing. The research will now be extended by the generation of curved-layer morphing origami architectures (i.e. individual layers with variable z-component actuation) to enable selective structural buckling; the generation of tubular bilayer/trilayer architectures; and, the generation of sequential actuation through the addition of porogens (i.e. dissolvable particles used to create porous hydrogel structures) such that the rate and magnitude of actuation can be further programmed in the design phase.
10:30 AM - SB04.04.07/SB01.04.07
Extreme Hydrogel Technology
Massachusetts Institute of Technology1Show Abstract
While human tissues and organs are mostly soft, wet and bioactive; machines are commonly hard, dry and biologically inert. Bridging human-machine interfaces is of imminent importance in addressing grand societal challenges in health, security, sustainability, education, and joy of living. However, interfacing human and machines is extremely challenging due to their fundamentally contradictory properties. At MIT Zhao Lab, we propose to harness “extreme hydrogel technology” to form long-term, high-efficacy, compatible and seamless interfaces between humans and machines. In this talk, I will first discuss the fundamental mechanisms to design extreme properties for hydrogels, including extremely tough, resilient, adhesive and anti-fatigue, for long-term robust human-machine interfaces. Then I will discuss a set of novel hydrogel technologies, including i). hydrogel bioelectronics capable of electro-opto-fluidic interrogating single neurons and continuously monitoring gastric physiological conditions over the long term; ii). tissue double-sided tapes that give instant strong adhesion of wet tissues and devices. I will conclude the talk with a perspective on future human-machine convergence enabled by extreme hydrogel technology.
11:00 AM - SB04.04.08/SB01.04.08
Smart Hydrogels from Mechanistic Design to Practical Applications
University of Akron1Show Abstract
Synthetic polymer hydrogels as soft-wet materials, consisting of three-dimensional cross-linked networks and a large amount of water (50–90%), possess many unique properties such as swelling/deswelling, stimuli-responsiveness, shock absorption, and low sliding friction, making them as potential excellent biomimetics for substitution of soft living materials. However, conventional hydrogels often suffer from weak mechanical properties, which greatly limit their extensive uses for many other applications. In this talk, we will present different design strategies to prepare tough and multifunctional hydrogels with unconventional polymer network architectures and extraordinary properties. Guided by our design principle, we will demonstrate different hydrogels with high mechanical properties, self-healing, actuation, antifouling, and/or wound healing to mimic cartilages, artificial muscles, and mussel-inspired glues. In parallel, molecular simulations will be presented to given atomic-details of structure-properties relationship. Finally, several unique aspects for future development of tough hydrogels will be suggested.
11:30 AM - SB04.04.09/SB01.04.09
Design and Understanding Dynamic Hydrogel with Hydrazone Crosslinks for 3D Printing
Junzhe Lou1,Sean Friedowitz1,Christopher Lindsay1,Sarah Heilshorn1,Jian Qin1,Yan Xia1
Stanford University1Show Abstract
Dynamically crosslinked hydrogels received increasing interest for their adaptive mechanical behaviors under stress and deformation and wide applications for cell scaffolding and delivery. We present a new concept of modulating the dynamics of hydrogel systems crosslinked by hydrazone bonds via a biocompatible organic catalyst. The catalyst accelerates the exchange kinetics of hydrazone bonds for over two orders of magnitude, resulting in identical network structure with widely tunable viscoelastic behavior. The catalyst control of network dynamics enabled quantitative and unambiguous correlation between the network parameters and mechanical properties of dynamic polymer networks, which can be generalized to provide design principles to engineer their viscoelastic properties. We also applied this system for 3D bio-printing to modulate the dynamic properties of hydrogels at different time points of application to have both high injectability and high stability. The incorporated catalyst enhanced the exchange of dynamic crosslinks to achieve high injectability during printing process, but rapidly diffused away from the hydrogel after ejection to retard the exchange and improve the long-term stability for cell culture.
11:45 AM - SB04.04.10/SB01.04.10
Chemical Pumps for Soft Autonomous Robots
Junsoo Kim1,Kai Luo2,Zhigang Suo1
Harvard University1,Beijing Institute of Technology2Show Abstract
Soft robots can be untethered by carrying a chemical fuel of pneumatic actuators. However, it has a fundamental design restriction; the fuel pressure should be higher than the actuator pressure to transport the fuel. Given that the fuel part occupies most of the volume, the robot becomes pressurized as much as the actuating pressure and requires stiffer materials for the fuel part, making entire robots stiffer. Here, inspired by the pit in plants, we decouple the pressures of the fuel part and the actuator while providing a fuel against the pressure gradient by introducing an isolator between them, thereby liberating from the design constraint. This isolator consists of a hydrophilic nano-porous membrane made of a hydrogel and a micro-porous wall made of a nylon mesh, that correspond to the pit membrane and the cellulose wall at the pit respectively. The mechanical integrity of the structure according to the geometry is studied by finite-element analysis to establish a design rule and the pneumatic power is extensively characterized experimentally with various parameters. Finally, the isolator is implanted to the conceptual soft robots to demonstrate the merits of the isolator.
Tuesday PM, December 03, 2019
Hynes, Level 3, Room 302
1:30 PM - SB04.05.01
Function-Function Relationships in Multifunctional Soft Actuators
Helmholtz-Zentrum Geesthacht1,University of Potsdam2Show Abstract
The limitation of classical shape-memory polymers of a stimuli-induced one time shape shift was overcome with the realization of shape-memory polymer actuators (SMPA). SMPA are soft actuators, which can repetitively change their shape reversibly controlled by temperature under stress-free conditions. They possess the unique feature of re-programmability of their actuation capability related to
shape changing geometry and switching temperature. The thermally controlled reversible actuation can occur many times [1,2]. Structure-function relationships for SMPA can be derived from datasets, which are generated by comprehensive characterization of the effects caused by systematically varying structural parameters on different length scales. Motivated by potential application, e.g. in the field of robotics or healthcare technologies require additional functions such as self-repair, magnetic controllability or degradability. Besides integrating these different functions in one material system, creation of targeted function-function relations are a major
challenge. Orthogonal multifunctionality is realized when several functions can be addressed almost independently from each other. An example for orthogonal functions are soft actuators equipped with a self-healing capability . Sequentially coupled functions enable linking functions according to a domino effect. Sequential multifunctionality relies on a series of functions, where the effect (output) of one function is the input of the next function. The coupling of a stimulus conversion from magnetic to thermal with an actuation capability will be presented as a prominent example .
 A. Lendlein, O. E. C. Gould, Nat. Rev. Mater. 2019, 4, 116.
 A. Lendlein, Sci. Robot. 2018, 3, eaat9090.
 M. Farhan, T. Rudolph, U. Nöchel, K. Kratz, A. Lendlein, Polymers 2018, 10, 255.
 L. Wang, M.Y. Razzaq, T. Rudolph, M. Heuchel, U. Nöchel, U. Mansfeld, Y, Jiang, O. Gould, M. Behl, K.
Kratz, A. Lendlein, Mater. Horiz. 2018, 5, 861.
2:00 PM - SB04.05.02
Hydrogels and Other Ionic Conductors in ‘Piezo-Ionic’ Sensors, Actuators and Electrochemical Devices
John Madden1,2,Yuta Dobashi1,2,Mirza Sarwar1,2,Dickson Yao1,2,Saeedeh Ebrahimi Takalloo1,2,Claire Preston1,2,Ngoc Tan Nguyen1,2,3,Justin Wyss2,1,Bertille Dupont2,1,Yael Petel1,Carl Michal1,Cédric Plesse4,Giao Nguyen4,Frédéric Vidal4,Eric Cattan3,Sébastien Grondel3,David Shepherd3,Geoffrey Spinks3
University of British Columbia1,Advanced Materials and Process Engineering Laboratory2,Université Polytechnique Hauts-de-France, IEMN-CNRS3,Université de Cergy-Pontoise4Show Abstract
Ionic conductors offer exciting device possibilities, particularly with the advent of highly extensible and easily synthesized hydrogels. Following on from recent work on hydrogel “ionic skin”, ‘piezo-ionic’ sensors and ionic artificial muscle, we present example ionic devices, including stretchable and transparent capacitive sensor arrays, pressure sensors that generate currents upon stretching, actuators that bend or contract when ions are inserted, as well as stretchable electrochromic elements and batteries.
Hydrogels and other ionic conductors offer advantages over metals and semiconductors in being intrinsically stretchable and non-absorbing of visible light. Their moderate to low moduli and non-linear mechanical properties can match those of tissue, and make them of interest for use in human interfacing devices. On the other hand, ions are much less mobile than electrons, ionic conductors don’t have bandgaps, and, unlike electrons and holes, anions and cations don’t recombine. The materials are typically wet, and properties can depend significantly on dimensions, pH and temperature. Given these drawbacks, how can we make practical use of ionic conductors?
In order to avoid being limited by the low mobility of ions, we can take two approaches. One is to implement gels and other ionic conductors in devices that consume very little current – such as capacitive sensor arrays. Even in low current devices, dropping temperatures can dramatically and unacceptably increase resistance, so a careful consideration of RC charging time is important in the design. Another approach to avoid being limited by low mobility is to make the transit distances short. We present bending actuators that can operate hundreds of hertz.
Relative speed of ion motion is important in ‘piezo-ionic’ sensors, where application of a pressure gradient leads to differential rates of ion motion between positive and negative ions – and the generation of current. NMR and electromechanical measurements suggest that in hydrogels ions move more slowly than solvent, perhaps hindered by the polymer structure. The small voltages that result are sufficient to stimulate nerves.
Electrochemical devices combine electronic and ionic conductors – for example in batteries, electrochromics and ionic diodes. In such cases, the electrode material is not as stretchable as the hydrogel. We present a symmetric conducting polymer-based electrochromic element that can stretch and change colour, and battery that is robust under extension.
If ionic devices dry out, they will slow or stop. One approach to avoid drying is to use salts that dramatically reduce vapour pressure – but this can come at the cost of conductivity. We instead demonstrate the use of non-volatile ionic liquids to keep a capacitive sensor array working for years without encapsulation. Alternatively, low vapour transmission rate elastomers can keep fast actuators and stretchable batteries functional for months or even years without preventing bending.
2:30 PM - SB04.05.03
Electrically Controlled Gel Actuator Using Liquid Metal Spring
Ken Matsubara1,Hiroki Ota1
Yokohama National University1Show Abstract
This report demonstrates an electrically controlled gel actuator by a three-dimensional(3D) helical structure with liquid metal. Previously, core-shell hydrogel microsprings was fabricated using a double bevel-tip nozzle. In this study, liquid metal as conductive materil was injected into core part of microspring, which formed liquid metal spring which has 3D helical structure. A rod of a thermoresponsive gel was inserted into the center of the liquid metal spring in order to an actuator. Current was applied to the spring to heat the entire actuator. The rod of temperature responsive gel was warmed up, and shrinks together with the spring . As a result, we succeeded in control the actuation of the gel by the liquid metal spring by 16%. Spring structures might be used in a wide range of fields taking advantage of energy absorption and storage. Our gel actuators present an important advancement towards development in several fields including soft robots, microactuators, drug delivery systems(DDS).
Background: Poly(N-isopropylacrylamide) [PNIPAM] is a temperature-responsive polymer that has lower critical solution temperature(LCST) at 32°C. PNIPAM gel exposed to an environment at higher than LCST changes hydrophilic to hydrophobic so that the water is discharged, and its volume decreases eventually. In several fields such as soft robotics and DDS, this characteristics is taken advantage of. However, in terms of an actuator using a temperature responsive gel, they require temperature change in entire environment, which make control of an individual actuator difficult. To improve this individual controllability, we propose a gel actuator that combines a heater using a liquid metal coil which is ultra soft, and a temperature responsive gel. In addition, the coil made of liquid metal has little change in cross-sectional area during the deformation, which leads stability of the resistance change. This helical shape overcomes the problem of changing parameters due to deformation that often occurs in soft actuators and stretchable sensors, and provide electrical control of gel actuation.
Fabrication: In order to create helical structure of gel by imbalance of crosslinking due to inclination of the nozzle, sodium alginate was poured from a bevel-tip nozzle into an aqueous solution of calcium chloride. Core-shell hydrogel helical structure was made by double nozzles held by a 3D printed nozzle joint. In this study, polyvinyl alcohol was used as a core part, and sodium alginate as a shell part. Then, the polyvinyl alcohol was extruded with liquid metal(Galinstan. Eventually, a spiral structure of Galinstan was established. Temperature responsive gel was molded by 3Dprinter. Then, the rod of the gel was inserted to the liquid metal microspring. Gel actuator with liquid metal coil was established.
Results: Characteristics of liquid metal microspring was investigated. Modules of microsprings filled with liquids metal in core parts were 0.33 N/m. we measured resistance change as a function of elongation of the straight and spiral wiring. The resistance of a straight wiring of the liquid metal increased to 140% by 100 % tension. On the other hand, a spiral wiring of the liquid metal increased to only 1.2 %. Therefore, we accomplished the liquid metal spiral wiring which maintained stable resistance in DC during harsh deformation of a circuit in this study. Furthermore, electrically controlled gel actuation was demonstrated. The gel actuator was heated by supplying 1.4W of power to liquid metal coil . As a result, it contracted 16% in 15 minutes. In summary, we succeeded in producing an actuator that can be controlled by electricity.
2:45 PM - SB04.05.04
Design with Supramolecular Hydrogels
Hector Lopez Hernandez1,Eric Appel1
Stanford University1Show Abstract
Supramolecular hydrogels are appealing for biological applications such as drug delivery, 3D printing bio-inks, and cell therapies. These applications create a diverse set of material requirements which are met by exploiting the broad tunability of the hydrogel’s material properties through modifications to the composition, crosslinking moieties, concentration, and molecular weight. The effects of these variables on the material properties can be complex and difficult to characterize. In addition, the vast parameter space makes it difficult to rationally design the hydrogels for specific applications.
Herein we present the complex rheological and diffusive behavior for supramolecular polymer-nanoparticle hydrogels, comprising hydroxypropyl methylcellulose and poly(ethylene glycol)-b-poly(lactic acid) nanoparticles, from the perspective of designing an injectable controlled release drug-delivery platform. The hydrogel’s associative gel formation dynamics and the strong non-Newtonian rheological behavior, including yield stress fluid behavior and shear-thinning, are presented as a function of variations in the formulation of the polymer-nanoparticle hydrogels. Diffusion, measured by fluorescence recovery after photobleaching (FRAP), is presented to demonstrate the correlation between the mechanical properties of the hydrogels and the transport within the hydrogel. It is shown that formulations created to expand the timescale of release may result in an inadvertent effect of increasing the viscosity and yield stress of the hydrogels, precluding injectability. We also present a design-oriented approach, developed from our systematic rheological and diffusive characterization, which allows for visualizing the effects of each formulation knob on intrinsic material properties and behavior. Furthermore, this approach allows for the generalization of the hydrogel platform and provides a means for engineering formulations for a more diverse set of applications beyond injectable therapeutics, such as 3D printing.
3:30 PM - SB04.05.05
Design of Novel Homocomposite and Hierarchically Structured Hydrogels for 3D Printing
North Carolina State University1Show Abstract
This talk will present two interrelated approaches to making novel classes of extrudable and responsive hydrogel materials based on special suspensions and multiphasic compositions. The first one uses a method called 3D printing with Homocomposite Thixotropic Paste (HTP). This method was originally developed in our group for 3D printing of ultrasoft silicone structures. The extrudable HTPs are “capillary gels” made of particles and binding liquid with the same chemical composition. At a certain volume fraction the pre-gelled particles jam and make a two-phase thixotropic homocomposite paste. Once this paste is extruded, the gelation of the liquid medium results in a homogeneous and cohesive single-component hydrogel. Its remarkable flexibility and extensivity are based on the strong cohesion of the particles and identical cured liquid. The HTP compositions allow for easy doping with magnetic nanoparticles to make them field-responsive. The mechanical properties of the homocomposite material can be enhanced further by using particles with special morphology and interactions. In the second part of the talk, we will show how the HTP-3DP method was enhanced by using a new class of hierarchically structured soft particles. The morphology of these “dendricolloid” particles is similar to molecular-scale polymer dendrimers, but is two orders of magnitude larger in scale. They are formed as a result of a new process of polymer precipitation in turbulently sheared liquid. The dendricolloids have very large excluded volume, while their nanofiber corona possesses the highly adhesive abilities of the nanofiber-padded gecko legs. The dendricolloids form strong gels at very low volume fractions. They produce even sturdier homocomposite and heterocomposite hydrogels when their medium is molecularly gelled on its own. The investigation of the interactions-structure-property relationship of such HTP 3D printed materials could enable the making of numerous hydrogel architectures with excellent mechanical properties and programmed response and actuation.
4:00 PM - SB04.05.06
A Photothermal Responsive Actuator with Self-Monitoring Strain Sensing Capability
Ximin He1,Chiao-Yueh Lo1,Cheolgyu Kim1
University of California, Los Angeles1Show Abstract
Soft robots, with their attractive living organism-like compliance and flexibility, have motivated the development of new active materials capable of neuromuscular behaviors. In spite of many new soft sensors and soft actuators, self-sensing materials that can monitor their own motions are highly desirable but proven challenging to realize. In this paper, we present a photothermally-responsive electrically conductive soft material that can serve as a strain sensor and a self-monitorable photothermal actuator, simultaneously owning two key functions essential to artificial muscle materials. This material is a nanostructured conductive hydrogel based on an interpenetrating network of theromoresponsive hydrogel and conducting polymer with enhanced stretchability and responding speed. A variety of complex photo-driven anisotropic locomotion of the homogeneous composite hydrogels can be precisely remotely controlled by near-infrared (NIR) laser illumination. The strain produced from the controlled motion is sensed by the actuator itself in real time. The photothermal response and electrical conductivity allow the hydrogel acts as a photo-triggered switcher. With this unprecedented capability of sensing the magnitude of the strain that the actuator produces, the robust, stretchable, and ultra-sensitive conductive hydrogels will lead to the next-generation soft robots with self-diagnostic feedback-controlled, higher level of autonomy.
4:15 PM - SB04.05.07
Mechanical Characterization of Graded Hydrogel/Polymer Interfaces to Assess Robustness
Andrew Tomaschke1,Archish Muralidharan1,Stephanie Bryant1,Robert McLeod1,Virginia Ferguson1
University of Colorado Boulder1Show Abstract
As our understanding of tissue engineering for cartilage repair has progressed, so has the complexity of scaffolds designed to repair cartilage defects. Early scaffold designs focused on getting cells into the defect using a soft, biocompatible materials like Pluronic and Polyglycolic acid . When outcomes proved undesirable due to inability of soft hydrogels to bear physiological loads, researchers designed scaffolds to mimic the properties of the native tissue . Unfortunately, these stiff scaffolds were highly cross-linked and as a result, had diffusional limitations that limited the ability of the cells to proliferate and create new tissue. Thus, recent approaches now utilize a composite design . These use a stiff polymer skeleton to control strain under externally applied loads and match the stiffness of surrounding tissues when implanted and a soft hydrogel cellular niche for cells to grow and proliferate. For this combined approach to be effective, it relies on the attachment of the soft cellular niche to the stiff skeleton in order to transmit the proper strains to the seeded cells.
Briefly, our approach includes a 3D stereolithography (SLA) manufactured, stiff PEGDA:PETMP structure (target modulus = ~1 MPa) that is infilled with a soft (~50 kPa), PEG-norborene hydrogel. The stiff structure bears load and controls strain, whereas the soft infilling hydrogel can be tailored [4,5] to serve as a cellular niche. To mitigate potential interfacial failure between the stiff structure and soft hydrogel, we have created a graded interface by creating a shell of 13% converted stiff material around a 100% converted core and infiltrating the 13% converted PEGDA:PETMP with PEG-norborene.
Preliminary testing of sharp versus graded interface materials showed that the graded interface more effectively resisted fracture when loaded in tension. However, this analysis lacks context of how specific property gradients (i.e., via spatial control of conversion) can be designed to minimize interfacial failure between the two materials. Thus, this work presents a direct assessment of the material property gradients spanning sharp and a range of graded interfaces. Using nanoindentation testing, the distribution of mechanical properties across the interfaces are characterized. These measures will be used to help explain the role of fracture across gradient conversion interfaces between two dissimilar materials. This work is designed to both validate our existing approach for interface design and serve as a guide to others seeking to utilize composite, SLA-printed scaffolds in their work.
 Liu, Yanchun, et al. "Repairing large porcine full-thickness defects of articular cartilage using autologous chondrocyte-engineered cartilage." Tissue engineering 8.4 (2002): 709-721.
 Bryant, Stephanie J., et al. "Encapsulating chondrocytes in degrading PEG hydrogels with high modulus: engineering gel structural changes to facilitate cartilaginous tissue production." Biotechnology and bioengineering 86.7 (2004): 747-755.
 Aisenbrey, Elizabeth A., et al. "A Stereolithography–Based 3D Printed Hybrid Scaffold for In Situ Cartilage Defect Repair." Macromolecular bioscience 18.2 (2018): 1700267.
 Fiedler, C. I., et al. "Enhanced mechanical properties of photo-clickable thiol–ene PEG hydrogels through repeated photopolymerization of in-swollen macromer." Soft matter 12.44 (2016): 9095-9104.
 Aisenbrey, Elizabeth A., and Stephanie J. Bryant. "A MMP7–sensitive photoclickable biomimetic hydrogel for MSC encapsulation towards engineering human cartilage." Journal of Biomedical Materials Research Part A 106.8 (2018): 2344-2355.
4:30 PM - SB04.05.08
From Aqueous Graphene Dispersions to Smart Soft Materials
The synthesis of different hybrid hydrogels by in situ radical polymerization in the presence of graphene derivatives, is one of the followed approaches to attain three-dimensional nanocomposite scaffolds. The role of the nanomaterial within the polymer network is primarily intended for the reinforcing (i.e. increasing the stiffness and toughness). However, we have shown that the presence of graphene can also enhance features such as biocompatibility, smart behavior based on responsiveness to external stimuli, sensing, or self-healing ability, giving rise to truly hybrid composites.
The preparation of these soft materials requires the production of large amounts of graphene derivatives in water, and for this reason, ball milling approaches developed in our labs, have proven a method of choice for the preparation of graphene starting dispersions. Moreover, aqueous graphene suspensions can be rapidly frozen and, subsequently, lyophilized giving rise to a very soft and low-density black powder which can be readily dispersed in water and in organic monomers allowing the preparation of the hybrid hydrogels.
4:45 PM - SB04.05.09
Artificial Phototropism and Artificial Phototaxis Based on Light-Sensitive Hydrogels
Yusen Zhao1,Xiaoshi Qian1,Ximin He1
University of California, Los Angeles1Show Abstract
Many living organisms track light sources and adaptively stop their movement when the tracking is achieved. This phenomenon, known as phototropism, occurs as plants self-orient to face the sun perpendicularly throughout the day. While many smart materials exhibit nastic behaviors in response to external stimuli, no synthetic material can intrinsically detect and accurately track the direction of stimuli, i.e., exhibit tropistic behaviors. Other than the phototropism in dynamic equilibrium state, oscillations are also widely found in living organisms to generate propulsion-based locomotion often driven by constant ambient conditions, such as phototactic movements. However, most man-made oscillations require non-constant energy input and cannot perform environment-dictated movement. Here we report an artificial phototropic and an artificial phototactic system by using the same light-sensitive hydrogel system, respectively, termed sunflower-like biomimetic omnidirectional tracker (SunBOT) and soft swimming robot (OsciBOT). The SunBOT can instantaneously aim to incident light in three-dimensional space over broad ambient temperatures. Phototropism successfully enabled plant-like maximization of energy harvesting through SunBOT-based omnidirectional solar vapor generation, achieving up to 400% energy harvesting enhancement over non-tropistic materials by maintaining normal to oblique illuminations. OsciBOT showcases agile life-like omnidirectional oscillatory motion in entire 3D space with near-infinite degrees of freedom. The large force generated by the powerful and long-lasting oscillation of OsciBOT can effectively self-propel away from light source, showing high-speed and controllable phototactic locomotion. The artificial phototaxis opens broad opportunities in maneuverable marine automated systems, miniaturized transportation, and solar sails.
Marc In het Panhuis, University of Wollongong
Namita Choudhury, RMIT University
Ferenc Horkay, National Institutes of Health
Jurgen Groll, University of Wurzburg
Marc In het Panhuis
Wednesday AM, December 04, 2019
Hynes, Level 3, Room 302
8:00 AM - SB04.06.01
Designing New Bioinspired 3D Hydrogels for Tissue Regeneration
Tel Aviv University1Show Abstract
Molecular self-assembly is a key direction in current nanotechnology based material science fields. In this approach, the physical properties of the formed assemblies are directed by the inherent characteristics of the specific building blocks used. Molecular co-assembly at varied stoichiometry substantially increases the structural and functional diversity of the formed assemblies, thus allowing tuning of both their architecture as well as their physical properties.
In particular, building blocks of short peptides and amino acids can form ordered assemblies such as nanotubes, nanospheres and 3D-hydrogels. These assemblies were shown to have unique mechanical, optical, piezoelectric and semiconductive properties. Yet, the control over the physical properties of the structure has remained challenging. For example, controlling nanotube length in solution is difficult, due to the inherent sequential self-assembly mechanism. Another example is the control of 3D-hydrogel scaffold’s physical properties, including mechanical strength, degradation profile and injectability, which are important for tissue engineering applications.
Here, in line with polymer chemistry paradigms, we applied a supramolecular polymer co-assembly methodology to modulate the physical properties of peptide nanotubes and hydrogel scaffolds. Utilizing this approach with peptide nanotubes, we achieved narrow nanotube length distribution by adjusting the molecular ratio between the two building blocks; the diphenylalanine assembly unit and its end-capped analogue. In addition, applying a co-assembly approach on hydrogel forming peptides resulted in a synergistic modulation of the mechanical properties, forming extraordinary rigid hydrogels. Furthermore, we designed organic-inorganic scaffold for bone tissue regeneration.
This work provides a conceptual framework for the utilization of co-assembly strategies to push the limits of nanostructures physical properties obtained through self-assembly.
Ghosh, M.; Halperin-Sternfeld, M.; Grinberg, I.; Adler-Abramovich, L. Nanomaterials 2019, 9, (4), 497.
Aviv, M.; Halperin-Sternfeld, M.; Grigoriants, I.; Buzhansky, L.; Mironi-Harpaz, I.; Seliktar, D.; Einav, S.; Nevo, Z.; Adler-Abramovich, L. ACS Appl. Mater. Interfaces 2018, 10, (49), 41883-41891.
Halperin-Sternfeld, M.; Ghosh, M.; Sevostianov, R.; Grogoriants, I.; Adler-Abramovich, L. Chem. Comm. 2017, 53, 9586-9589.
Ghosh, M.; Halperin-Sternfeld, M.; Grigoriants, I.; Lee, J.; Nam, K. T.; Adler-Abramovich, L. Biomacromolecules 2017, 18, (11), 3541-3550.
8:15 AM - SB04.06.02
Biofabrication with Bioinks Made of Spider Silk
University of Bayreuth1Show Abstract
Biological materials often exceed the characteristics and properties of man-made ones. One well-known example is spider silk with superior mechanical properties such as strength and toughness. Here, recombinant spider silk proteins will be introduced as one material to be used in bioinks for biofabrication. Proteins reflect one fascinating class of natural polymers with huge potential for technical as well as biomedical applications.
We have developed biotechnological methods using bacteria as production hosts, which produce structural proteins mimicking the natural ones. Besides the recombinant protein fabrication, we analyzed the natural assembly processes and we have developed spinning techniques to produce protein threads closely resembling natural fibers. In addition to fibers, we employ structural proteins in other application forms such as hydrogels, particles or films with tailored properties. Especially hydrogels can be employed as new bioinks for biofabrication.
Their elastic behavior dominate over the viscous behavior over the whole angular frequency range with a low viscosity flow behavior and good form stability. No structural changes occur during the printing process, and the hydrogels solidify immediately after printing by robotic dispensing. Due to the form stability it is possible to directly print multiple layers on top of each other without structural collapse. Cell-loaded spider silk constructs can be easily printed without the need of additional cross-linkers or thickeners for mechanical stabilization. Encapsulated cells show good viability in such spider silk hydrogels. Current examples in the lab are bioinks made of spider silk hydrogels and cardiomyocites to be 3D printed into patches for heart muscle tissue repair.
8:30 AM - SB04.06.03
Biophysics of Complex N-glycan Shields on HIV Pseudovirus
Howard University1Show Abstract
The surface of cells and pathogens is coated with a layer of carbohydrates called glycans. Majority of glycans on secreted and membrane proteins is produced by the N-glycosylation pathway and are known as N-glycans. N glycans have either (i) core and distal branches of mannose sugars (high-mannose type) or (ii) core of three mannose sugars followed by distal branches of non-mannose sugars that end in sialic acid (complex type). Our goal is to understand in the inherent biophysical design in the choice and placement of the complex N-glycan sugars. Single sugar biophysics obtained with force spectroscopy was integrated to composite N-glycan biophysics by systematically increasing the complexity of sugar presentation in monolayer-monolayer to virus-monolayer to virus-virus experiments. In all systems, there were consistent long-ranged, charge-mediated, and materially ‘tough’ self-adhesions originating from sialic acid residues. On the other hand there were more short-ranged, hydrogen-bonding mediated, and materially ‘brittle’ self-adhesions originating from mannose residues. The two sugars did not cross-interact and neither did most other sugars in the glycan shield. Correspondingly in solution, mannose-stabilized gold nanoparticle tightly coated viruses, but sialic-stabilized gold nanoparticle particles aggregated and precipitated viruses. Moreover, the sugar interactions in the glycan shield gave rise to a rate-dependence, with both the virus glycan shield and virus itself being penetrated at low rates but only compressed at high rates. The findings imply that biological surfaces would have different interfacial properties and aggregation propensities based on the sugar composition of the surfaces and the solvent shear.
9:00 AM - SB04.06.04
Vascularized Bone Grafts Prepared with Hydrogel Micro-Dispenser and 3D Mesh Printing
Hikaru Akieda1,Tatsuto Kageyama1,Yohei Noda1,Shoji Maruo1,Junji Fukuda1
Graduate School of Engineering, Yokohama National University1Show Abstract
Large bone defects are serious complications typically caused by extensive trauma, tumors, infections, and congenital musculoskeletal disorders. Current approaches to treat bone defects include autograft and allograft transplantation. However, limited availability of grafts, infections, and immune rejection hinder the widespread application of these approaches. Recently, tissue engineered bone grafts using osteogenic cells and/or osteoconductive materials have emerged as a promising approach for treating large bone defects. However, their therapeutic use remains limited due to the significant time required for ossification and remodeling of large grafts after transplantation. To shorten the required time, pre-vascularization of grafts may be critical, because vasculature delivers not only oxygen and nutrients, but also osteogenic cells for bone formation and subsequent remodeling. In this study, we propose an approach for fabricating vascularized bone grafts containing osteoblasts, bone matrix, and complex vasculature. A unique aspect of our approach is that we first prepare collagen-rich cell aggregates, named bone beads, through the spontaneous constriction of cell-encapsulating collagen drops through cell attraction. Mesenchymal stem cells were encapsulated in 2 µl collagen microgels, which spontaneously contracted from a diameter of 2 mm to that of less than 500 μm during a 24 h culture. This spontaneous formation of bone beads facilitated large scale bone bead preparation using a micro-dispenser system. This approach allowed the spotting of 10,000 collagen microgels in 10 minutes. After gelation at 37 °C for 30 min, constructs were collected, suspended in culture medium, and seeded onto a non-cell adhesive dish or spinner flask bioreactor. Interestingly, cells in bone beads showed better osteogenic differentiation, including osteogenic marker expression and bone matrix secretion, compared with conventional spheroid culture after 2 weeks in an osteogenic differentiation medium. We further optimized the stirring rate of the spinner flask bioreactor to maximize osteogenic differentiation of cells in bone beads. In particular, bone matrix secretion was significantly increased by increasing the stirring rate from 0 to 250 rpm. To fabricate vascularized bone grafts, a few hundred bone beads were cultured for 14 days. They were then suspended intermixed with vascular endothelial cells and seeded into non-cell-adhesive flat-bottom dishes. After 1 day of culture, these constructs were stacked into a cell culture insert for 2 days of further culturing. Endothelial cells formed luminal structures in the spaces between bone beads. Fabricated vascularized bone grafts were transplanted into 4-mm-diameter cranial bone defects in nude mice, and bone regeneration efficiency was evaluated by micro computed tomography. Five weeks after transplantation, vascularized bone grafts achieved 83% coverage of the bone defect area, which is significantly greater than that achieved using other approaches, such as the use of beta tricalcium phosphate (β-TCP) powder. Moreover, histological analysis showed newly formed bone at transplanted sites. Finally, to hold bone beads in place at bone defect sites, we tailor-made β-TCP meshes using a 3D printer. Transplantation of bone-bead-loaded β-TCP meshes showed higher bone regeneration at bone defect sites than transplantation of β-TCP mesh alone. This simple approach using a micro-dispenser and a 3D printer may provide a promising strategy for advancing bone regenerative medicine.
9:15 AM - SB04.06.05
Fabrication of Universal Thermoresponsive Cell Culture Platform—Toward a New Horizon in Tissue Engineering
Andrew Choi1,Kyoung Duck Seo2,Hyungjun Yoon1,Seon Jin Han1,Dong Sung Kim1
POSTECH1,Wonkwang University2Show Abstract
Over the course of years, a cascade of studies has engaged in enhancing the health of mankind scrutinized diverse biomaterials (metals, ceramics, polymers, hydrogels, and etc.) for the development of novel and innovative cell culture platforms. And inevitably continued expansion in material selectivity of cell culture platform enabled the creation of diverse cell culture platforms with increased functionalities. One of the most intriguing functional cell culture platforms utilizes the thermoresponsive hydrogel, poly(N-isopropylacrylamide (PNIPAAm), which possesses a prominent behavior of reversibly altering its physicochemical characteristics in response to change in temperature; and consequently, enables the harvest of cell sheets in a scale of 102 mm by altering the ambient condition of temperature above/below low critical solution temperature (LSCT) of 32 °C without any use of chemical treatment. However, its common fabrication method (grafting method) currently confronts several issues due to the instability of grafted polymer chains on the substrate. Depends on the type of the substrate that polymer chains are being grafted and the fabrication methods that are being utilized to graft polymer chains, thermally triggered intermolecular interactions of the grafted polymer chains were found to be all different. And therefore, it is still arduous to achieve stable adhesion behavior of the cells on the fabricated cell culture platform and the inherently constrained geometry of the harvested cell sheet limits the range of its utilization. While the realization of various methods of adopting PNIPAAm on cell culture platform is continuously being pursued to attain in vivo-like heterogeneous or vascularized cell sheets, there are clear fundamental issues in the current ‘form’ of PNIPAAm cell culture platform that hamper maximizing the potential of cell sheet engineering.
In this study, we tailored the polymer network of conventional PNIPAAm through the modification of its substance composition and for the first time introduce a thermoresponsive cell culture platform composed only in a ‘bulk’ form of a PNIPAAm hydrogel having an MPa-scale Young’s modulus. While the initial surface roughness of the bulk PNIPAAm could be modulated by altering the cross-linker concentration, the value of the roughness was found to be changing from nm- to μm-scale above/below the LCST. Through the proper adjustment in the concentration of the cross-linker inside of the bulk PNIPAam, a stable attachment and easy detachment of diverse cells were allowed. During the incubation of cell lines (C2C12 and NIH3T3) at a temperature condition of 37 °C, all cells were able to be attached on the prepared PNIPAAm cell culture platform with the roughness value of below ~ 50 nm. On the other hand, the primary cells were found to be only attached on a surface with the roughness value of below ~30 nm during the incubation at the same condition. Moreover, in the act of detaching cell sheet via incubating them at a temperature condition of 20 °C, the cell sheets consists of cell lines were fully detached from the surface with the roughness value of ~10 μm or higher, whereas the cell sheets consists of primary cells were detached from the surface with a roughness of ~19 μm or higher. Based on such behavior of the diverse cells on prepared PNIPAAm cell culture platform, this study successfully optimized the surface roughness value and suggested a universal thermoresponsive cell culture platform which allows the harvest of all types of cell sheets consists of cell lines (C2C12 and NIH3T3) or primary cells (human umbilical vein endothelial cells and keratinocytes). We believe this novel universal cell culture platform could play a powerful and versatile role in igniting a spark to the advancement of cell sheet engineering.
10:00 AM - SB04.06.06
The Visco-Elasticity of 2D Protein Networks—Implication for Stem Cell Expansion at Liquid-Liquid Interfaces
Julien Gautrot1,Dexu Kong1,Lihui Peng1
Queen Mary, University of London1Show Abstract
The mechanical behaviour of the extracellular matrix has an important impact on cell phenotype. Despite the importance of mechanotransduction in regulating a wide range of phenotypes, we recently reported the surprising observation that cells (keratinocytes and mesenchymal stem cells) can adhere, spread and proliferate at the surface of liquids1-3. This observation is particularly surprising as the reinforcement of cell adhesion is thought to require a solid elastic or viscoelastic substrate that can resist cell-mediated contractile forces. Our work has evidenced the formation of protein nanosheets, self-assembled at the liquid-liquid interface, displaying strong mechanical properties that can provide a sufficient mechanical scaffold to promote cell adhesion and expansion. We showed that this is sufficient to regulate stem cell phenotype. However, the parameters controlling the self-assembly and the mechanical properties of protein nanosheets remain poorly understood. In this work we investigate the assembly of polymers and proteins at liquid-liquid interfaces, and the impact of pro-surfactants with a wide range of chemistries. We identify structural features that control the visco-elastic properties of the resulting nanosheets and regulate associated cell phenotype. In this work, we show the importance of parameters such as pH and concentration on protein self-assembly and the impact it has on interfacial mechanics. Importantly, we demonstrate the impact that pro-surfactant-protein interactions play on regulating the assembly and the interfacial mechanical properties of the corresponding interfaces. In addition, we show how these parameters regulate interfacial viscoelasticity over a wide range, and ultimately regulate cell adhesion and proliferation. Finally, we demonstrate the proof-of-concept of using such liquid substrates, in the form of emulsions, for stem cell culture in 3D bioreactors, and their simple recovery by centrifugation. Overall, our results suggest that nanoscale mechanical properties of biomaterials may dominate over bulk physical properties. This concept has important implications for the design of biomaterials in the field of regenerative medicine and allow the rational design of liquid substrates for tissue engineering.
Funding from the Leverhulme Trust (RPG-2017-229, Grant 69241), the ERC (ProLiCell, 772462) and the China Scholarship Council (201708060335) is gratefully acknowledged.
 Kong et al., Nano Lett. 2018, 18 (3), 1946-1951.  Kong et al., Faraday Discuss. 2017, 204, 367-381.  Kong et al., ACS Nano 2018, 12 (9), 9206-9213.
10:30 AM - SB04.06.07
Thermoresponsive Hydrogel Scaffolds with Cysteine Pendant Groups Show Enhanced Mucoadhesion
Ninad Kanetkar1,Adam Ekenseair1
Northeastern University1Show Abstract
Introduction: Inflammatory Bowel Disease (IBD) affects 1.9 million people in the United States1. Current treatments demand invasive surgery and lifelong immunosuppression that lead to poor quality of life. Systemic stem cell delivery has been shown to regenerate damaged tissues, however cell viability and therefore effectiveness remain suboptimal2. In situ forming biomaterial scaffolds can overcome this limitation by sustaining non-invasively delivered cell populations for a longer duration. Poly(N-isopropylacrylamide) (pNiPAAm) is a polymer that forms a gel above a Lower Critical Solution Temperature (LCST) of 32°C due to a shift in the balance between hydrophobic and hydrophilic interactions. pNiPAAm copolymers have been investigated as in situforming scaffolds due to the proximity of its LCST to body temperature. Previous research has established the ability of p(NiPAAm–co–Glycidyl Methacrylate (GMA)) thermogelling macromer (TGM) to be delivered to the intestine via an airbrush spray and sustain encapsulated cells3. Here, cysteine pendant groups were introduced on the polymer to covalently bind to the intestinal mucus, a hydrogel composed of cysteine rich proteins called mucins. The amine in cysteine reacts with epoxides on TGM with high specificity. Sulfhydryl groups on cysteine form disulfide bonds with other sulfhydryl motifs abundant in mucins. This work investigated the kinetics of cysteine conjugation, crosslinking, viability of encapsulated cells, and the impact on mucoadhesion.
Materials and Methods: TGM was obtained by copolymerization of pNiPAAm and GMA in a 10:1 mole ratio3,4. Cys-TGM was obtained by reacting 0.1 equivalents of Cysteine with a 10% TGM solution at room temperature. DSC, GPC, NMR spectroscopy, and rheometry were used for characterization. Crosslinking behavior was studied by obtaining sol-gel fractions under varied conditions. Cell viability was evaluated by LIVE/DEAD assay. Mucoadhesion was determined by the pull-off force required to separate two pieces of porcine intestine bound with the polymer.
Results & Discussion: The progress of cysteine conjugation was followed over time using DSC. The peak LCST of Cys-TGM increased from 30.24 to 32.05, and can be attributed to the increased hydrogen bonding in Cys-TGM, requiring higher energy to undergo a coil-globule transition to form a gel. Whereas TGM exhibited fully reversible thermogelation, Cys-TGM formed crosslinked gels which remained insoluble upon cooling below LCST. This network formation was accelerated when the gels were kept in a thermogelled state over several hours as confirmed by the net movement of the polymer from sol phase to gel phase. This indicated network formation, which reached a critical point at 4 hours of incubation and was complete after 6 hours. Cysteine conjugated TGM showed superior adhesive strength compared to unmodified TGM and a significant increase compared to a mucus-only control. LIVE/DEAD staining showed cells encapsulated in unmodified TGM initially showed higher death in comparison with the cysteine containing gels. Gels with 30% equivalent cysteine showed similar low death compared to 50% equivalent cysteine gels but showed a higher migratory behavior as opposed to clustered proliferation.
Conclusions: Cysteine modified thermogelling polymers were synthesized, characterized and tested in the context of applicability as an intestinal scaffold. Cysteine-mediated disulfide bond formation was shown to be a promising pathway to enhance scaffold mucoadhesion. Cysteine modification did not hinder the viability of encapsulated cells cultured over a long term.
1. NIDDK [https://www.niddk.nih.gov/health-information/health-statistics/digestive-diseases.] (Accessed: 10th February 2018)
2. Mooney, D. J. & Vandenburgh, H., Cell Stem Cell2,205–213 (2008).
3. Pehlivaner Kara, M. O. & Ekenseair, A. K., J. Biomed. Mater. Res. - Part A104,2383–2393 (2016).
4. Ekenseair, A. K. et al., Biomacromolecules13,1908–1915 (2012).
10:45 AM - SB04.06.08
In Situ Formation of Cell-Containing Hydrogel Sheets Conformal to Full-Thickness Burn Wounds
Richard Cheng1,Gertraud Eylert1,2,Jean-Michel Gariepy1,Sijin He1,Marc Jeschke1,2,Axel Guenther1
University of Toronto1,Sunnybrook Research Institute2Show Abstract
The current standard of care for treating patients with severe large area burns involves the direct application of a bilayered matrix consisting of a silicone layer for immediate wound coverage and a crosslinked collagen layer as a scaffold for host cell migration. Cell repopulation remains a challenge especially as acellular scaffolds rely on the recruitment of host cells. While emerging treatment options including the delivery of allogeneic or autologous cells via spraying or injection have demonstrated improved wound healing, the consistent delivery of cellularized biomaterials conformal to wound topologies remains a challenge.
Here, we report a handheld instrument for the in-situ formation of cell-containing biomaterial sheets conformal to a burn wound. The mesenchymal stem cell (MSC)-containing, fibrin-based bioink and thrombin crosslinker solutions are delivered through on-board syringe pumps to a microfluidic printhead with internal bifurcated channels. A skin precursor sheet of consistent thickness covered with the crosslinker is obtained at the exit. Wound-conformal delivery of MSC-laden biomaterial sheets was achieved by translating the printhead along the wound surface by a soft silicone wheel, while a two-axis gimbal design allowed it to adapt to the wound topology. We observed that the addition of 1% hyaluronic acid (HA) provided desirable shear-thinning behavior of the bioink (1.2 Pa*s at shear rate 1/s; 0.35 Pa*s at shear rate 100/s), resulting in 83% of the starting thickness to be maintained for deposition surfaces with inclination angles of 45 degrees. Furthermore, these fibrin-HA hydrogels maintained high biocompatibility with the co-delivered MSCs (>94%), in addition to long-term preservation of 3D morphology and cell proliferation as shown with Hoechst/Phalloidin+ immunostaining over one week. To demonstrate the clinical utility of this approach, we uniformly distributed 1x106 MSCs/ml of the fibrin-HA hydrogel on a porcine 5cm x 5cm full-thickness burn wound model and quantified a 1.4-fold improvement of macroscopic re-epithelialization speed, a 1.3-fold increase in collagen density in the dermal layer, and a 2.5-fold reduction in CD11b+ inflammatory cell activity after 28 days compared to burn only controls, as observed via microscopic analysis of H&E histological stains. Taken together, these results highlight the utility of in-situ delivering cell-containing bioinks conformal to physiological surfaces, while promoting cell viability and migration to accelerate wound healing in full-thickness burns.
11:00 AM - SB04.06.09
Cell-Friendly, Low-Cost and Fast Assembled Orthopaedic Treatment Using Hybrid Polycaprolactone/Alginate Hydrogel 'Bone Bricks' for Refugees
University of Manchester1Show Abstract
Physical, sensory or intellectual impairments affect one in every five refugees, a further one in seven is affected by a chronic disease and one in 20 suffers from injury. A 2016 Handicap International report stated that 53% of injuries were due to the use of explosive weapons, among this 47% of refugees had fractures or complex fractures and this includes open fractures of lower and upper limbs. Orthopaedic surgical intervention is a priority after blast injuries to align broken bones/fixate, treat infection and implement solutions for the associated bone loss. However, often the only feasible treatment for these injuries is limb amputation. Amputation has associated complications including heart attack, slow wound healing and infection.
This project aims to create a medical implant allowing for non-union bone loss of 10-20 cm in the lower limb able to induce bone regeneration. The research is built on the current treatment of external fixation but with the addition of an engineered internal prosthetic implant to improve patient outcomes, avoid painful limb lengthening and reduce recovery time. The patient specific prosthetic is achieved by constructing the prosthetic implant from modular pieces, “bone bricks”. The bone bricks, are hybrid scaffolds consisting of different biocompatible and biodegradable materials and infection prevention hydrogel, manufactured using multi-head extrusion-based 3D printing technique, come in a pallet of shapes and sizes and fit together in a “lego like” way to form the prosthesis. The prosthesis and paste will prevent infection, promote bone regeneration creating a mechanically stable bone union. The external fixator offers a comfortable support for patients and a strong stimulation to facilitate bone ingrowth.
This paper reports preliminary results using polycaprolactone/alginate hydrogels scaffolds. Scaffolds are extensively characterised in terms of morphology, physical, chemical and biological properties, and the results show that these scaffolds are suitable candidates to treat large bone defects enabling limb salvage as an alternative to amputation, avoiding painful limb lengthening and improving recovery time/functional patient outcomes.
11:15 AM - SB04.06.10
Novel Hydrophilic/Hydrophobic Thermo-Responsive Platforms from Citric Acid Crosslinked Methylcellulose Hydrogels
Lorenzo Bonetti1,Luigi De Nardo1,2,Fabio Variola3,Silvia Farè1,2
Politecnico di Milano1,National Interuniversity Consortium of Materials Science and Technology (INSTM)2,University of Ottawa3Show Abstract
Methylcellulose (MC) hydrogels undergo sol-gel reversible transition upon temperature changes. At temperatures higher than their lower critical solution temperature (LCST) they are in a gel, hydrophobic state. Conversely, at T < LCST they are in a sol, hydrophilic state . These hydrogels lend themselves to smart system applications, exploiting the body temperature as a trigger to activate their sol-gel transition [1,2]. However, one of the limiting factors of MC hydrogels consists in their reduced stability and mechanical properties . The purpose of our research is to explore a novel method to crosslink MC hydrogels in order to increase their mechanical properties while preserving their smart behavior.
A crosslinking strategy based on the employment of citric acid (CA) was developed. The thermal response of the gels was studied by using a Design of Experiment approach, analyzing the effect of three independent variables, namely CA concentration [1-5% w/w], crosslinking time [1-15 min], and crosslinking temperature [165-190 °C] on the swelling rate of the hydrogels. This approach allowed to identify three crosslinking conditions (low, medium, high) while avoiding a trial-and-error approach. The resulting crosslinked hydrogels were characterized by a physico-chemical, mechanical and in vitro biological point of view.
Swelling tests in water revealed the effectiveness of CA crosslinking in modulating the water uptake of MC hydrogels. The crosslinking density  increased from (0.19 ± 0.02)*10-4 to (2.58 ± 0.65)*10-4 mol cm-3 for low and high crosslinking conditions, respectively. FTIR analysis and acid-base titrations confirmed the efficacy of CA in controlling the crosslinking degree of the hydrogels . Specifically, carboxylic esters increased from 0.05 ± 2.74 to 42.25 ± 3.71 mmol/100 g for low and high crosslinking conditions, respectively. The extent of hydrophilic/hydrophobic transition was assessed by swelling tests in solvents with different polarities (water and 70% 2-propanol solution) and at different temperatures (4, 25, 37 and 50 °C) . These tests showed that both low and medium crosslinking conditions preserved the smart behavior of MC hydrogels. Ongoing studies aim at assessing temperature-induced chemical and nanomechanical variations assessed by Raman spectroscopy and Atomic Force Microscopy. In vitro biological characterization proved the absence of any cytotoxic effect induced by CA or by the crosslinking procedure when extracts were put in contact with L929 cells for 24 h.
The obtained results pave the way for the development of MC smart hydrogels with tunable properties, with potential innovative implications in the field of smart systems, e.g. for drug delivery.
 Altomare et al., J. Mater. Sci. Mater. Med. (2016)
 Gupta et al., Biomaterials (2006)
 Cochis et al., Materials (2018)
 Varma et al., Acta biomater. (2014)
 Coma et al., Carbohydr. Polym. (2003)
 Munoz-Pinto et al., J. Biomed. Mater. Res. A (2012)
11:30 AM - SB04.06.11
Room-Temperature Formed PEDOT:PSS Hydrogels Enable Injectable, Soft and Healable Organic Bioelectronics
Yihang Chen1,Shiming Zhang1,Ali Khademhosseini1
University of California, Los Angeles1Show Abstract
There is an increasing need to develop conducting hydrogels for bioelectronic applications. In particular, PEDOT:PSS hydrogels have gained significant focus due to their excellent biocompatibility and stability . However, injectable PEDOT:PSS hydrogels have not yet been reported. Such syringe-injectable hydrogels are highly desirable for minimally invasive biomedical therapeutics . Here, we demonstrate an approach to enable injectable PEDOT:PSS hydrogels by using room-temperature crosslinked PEDOT:PSS hydrogels (RT-PEDOT:PSS hydrogels). These RT-PEDOT:PSS hydrogels formed spontaneously after syringe-injection, without the need of any thermal treatments. We further demonstrate that these RT-PEDOT:PSS hydrogels can be used for soft and self-healable bioelectronics.
1. Lu, B.; Yuk, H.; Lin, S.; Jian, N.; Qu, K.; Xu, J.; Zhao, X., Pure PEDOT:PSS hydrogels. Nature Communications 2019, 10 (1), 1043.
2. Liu, J.; Fu, T.-M.; Cheng, Z.; Hong, G.; Zhou, T.; Jin, L.; Duvvuri, M.; Jiang, Z.; Kruskal, P.; Xie, C.; Suo, Z.; Fang, Y.; Lieber, C. M., Syringe-injectable electronics. Nature Nanotechnology 2015, 10, 629.
11:45 AM - SB04.06.12
Shining a Light on Mechanotransduction—Photo-Patterned Hydrogels for Tissue Engineering
Phillip Chivers1,2,Simon Webb1,Paul Genever2,David Smith2
University of Manchester1,University of York2Show Abstract
The high demand for transplant tissue is a major health concern worldwide. A shortage of donors combined with poor long-term outcomes post-transplant has seen tissue engineering emerge as an alternative therapy. Using a patient’s own stem cells to regenerate lost or damaged tissue could reduce pressure on transplant waiting lists and avoid issues of organ rejection. However, for laboratory research to be translated into clinical applications, the development of biomaterials which stimulate the formation of specific tissues is essential.1
In recent years, hydrogels have become leading candidates as scaffolds for controlled cell growth. Despite this, there is a dearth of literature exploring the applications of low-molecular-weight gels (LMWG) in this field.2 These materials, which self-assemble through non-covalent interactions, are often dynamic – able to modulate their structure and properties in response to their external environment. Such responsive materials have great potential for complex control of stem cell fate through the delivery of spatiotemporally defined cues.
We report the use of LMWG-containing materials for the spatial control of mesenchymal stem cell (MSC) behavior. By combining DBS-CONHNH2 (a LMWG) with a photo-curable polymer gel (PEGDM), we were able to modify the stiffness of the gels with spatial control by exposing specific regions to UV irradiation.3 MSCs grown on stiffer gels were significantly more likely to differentiate into bone cells than those cultured on soft gels. Furthermore, MSCs at each side of an interface between soft and stiff gel showed significantly different behavior, illustrating the potential of these patterned materials to direct stem cell growth. Studies into the controlled release and diffusion of model compounds and biomolecules indicate that these heterogeneously structured materials could be used for spatially-defined presentation of other stem cell directing factors in the future.
Temporal changes in gel stiffness can be used to impart a further level of control over MSC behavior. We are currently developing a family of hydrogels which modulate their mechanical properties through a reversible photoreaction. Using these materials, we aim to understand and exploit the influence of stem cell mechanical memory to develop next-generation biomaterials.
1 Webber, M. J.; Appel, E. A.; Meijer, E. W.; Langer, R. Nat. Mater., 2016, 15, 13-26
2 Christoff-Tempesta, T.; Lew, A. J.; Ortony, J. H. Gels, 2018, 4, 40
3 Chivers, P. R. A; Smith, D. K. Chem. Sci. 2017, 8, 7218-7227
SB04.07: Fundamentals and Applications I
Wednesday PM, December 04, 2019
Hynes, Level 3, Room 302
1:30 PM - *SB04.07.01
Failure and Fracture of Hydrogels and Hydrogel Composites
East Carolina University1Show Abstract
Hydrogels have gained recent attention for biomedical applications due to their large water content, which imparts biocompatibility. However, their mechanical properties can be limiting. There has been significant recent interest in the strength and fracture toughness of hydrogel materials in addition to their stiffness and time-dependent behavior. Hydrogels can fail in a brittle manner even though they are extremely compliant. In this work, the failure and fracture of hydrogels is examined using a range of mechanical test methods, including compression, tension, mode I fracture and mode III tearing. Spheres of commercially-available sodium polyacrylate were tested to failure in compression as a function of loading rate. The spheres exhibited virtually no load relaxation when compressed to small fixed displacements. The distributions of strength values obtained were examined in a particle fracture framework previously developed for brittle ceramics. Mode I and mode III fracture experiments were conducted for single-component hydrogels and for hydrogel composites reinforced by nanofibers. Even though the fibers were themselves also hydrogels, the composite toughness values were two orders of magnitude greater than those for the component gels. Strength and toughness of composite hydrogels approached values seen in natural soft biological tissues, indicating that a biomimetic approach to microstructure relates to increasing material properties of hydrogels, making them suited for use as tissue engineering scaffolds in demanding load-bearing applications such as articular cartilage in the joint.
2:00 PM - *SB04.07.02
Coarse-Grained Model of the Influence of Solvation on the Properties of Electrolyte, Nanoparticle and Polyelectrolyte Solutions
National Institute of Standards and Technology1Show Abstract
The aqueous solvation of ions, highly charged nanoparticles and polymers, and the resultant non-trivial interactions between these solvated species, is a ubiquitous, but poorly understood phenomenon that underpins many biological and manufacturing processes. This solvation phenomenon is investigated based on simple, but explicit, model of the solvent that accounts for the high cohesive interaction strength of water based on the constraint that the solvent reproduces the critical temperature of pure water, while the strength of the van der Waals ion-solvent interactions between the ions and the solvent are fixed by the experimentally observed enthalpy of solvation. We find that this coarse-grained model of aqueous ionic solutions reproduces observed trends of the viscosity of water and water diffusivity with specific salt types, along with observed trends in the density, compressibility and surface tension of aqueous solutions. The application of this model to highly charged particles and polyelectrolytes, leads to new phenomena associated with nanoparticle and polymer solvation that are not observed when the solvent is treated as a continuum. In particular, while the counter-ions dissolve into the solvent as in the case of a continuum solvent, they continue to dynamically associate, leading to the formation of a diffuse “polarizable” cloud of counter-ions around the polymers and nanoparticles. We find that the fluctuations of the ions of opposite charge, which are modulated by competitive counterion and polymer/particle solvation, can lead to strong attractive interactions between charged species having a common sign. We argue that these solvation-induced interactions are crucial for understanding the widespread observations of supramolecular assembly in highly charged polyelectrolyte and colloidal solutions in the context of viscoelastic solutions and gels of proteins, and many other naturally occurring polyelectrolytes, and in common charged colloidal viscolelastic materials such as soils, setting concrete, etc. Further development of this type of model for hydrogels, and many other aqueous solution applications, requires improvements in the modeling of ion-ion interactions and van der Waals solvent-polymer or nanoparticle interactions that become large when the salt concentration becomes large. Further validation studies of the coarse-grained model for transport coefficients such as ion diffusivity, etc. are also required.
3:30 PM - SB04.07.03
Behavior of Polyelectrolyte Gels in Concentrated Solutions of Highly Soluble Salts
Jessica Sargent1,John Howarter1,Kendra Erk1,Mitchell Brezina1,Xunkai Chen1,2
Purdue University1,University of California, Berkeley2Show Abstract
Hydrogels composed of lightly crosslinked poly(sodium acrylate-co-acrylamide) (P(ANa-AM)) have been investigated as responsive materials for a wide range of applications. This polyelectrolyte network is highly hydrophilic and sensitive to changes in the pH and ionic strength of its environment. Above a pH of ~5, the sodium acrylate moieties dissociate to produce negative charges along the polymer chain, which increases the gel’s swelling capacity due to a further increase in the osmotic pressure difference between the gel interior and the surrounding aqueous solution. However, if the solution in which the gel is submerged contains free cations (e.g., dissolved salt ions), these ions interact with the charged polymer molecules and reduce the gel’s swelling capacity and, consequently, transport properties. P(ANa-AM) gels have been applied in many biological applications and consumer products, and they are also a prime candidate for controlled release agents in internally cured high-performance concrete. The effects of biologically-relevant saline solutions on the swelling properties of these gels have been thoroughly investigated, but little has been reported regarding the performance of P(ANa-AM) gels in concentrated saline solutions (e.g., 10 mM to greater than 1 M) or after cyclical swelling and deswelling in saline solutions. In particular, it is expected that the effect of crystal formation of monovalent and multivalent salts within the gels from these concentrated solutions will have significant impacts on hydrogel behavior as well as offer new avenues for tailoring gel compositions for applications such as controlled crystal growth and recyclable hydrogel materials.
This research probes the effects of concentration, valency, and crystallization of highly soluble salts (e.g., sodium chloride and calcium chloride) on fundamental hydrogel properties including swelling capacity, mesh size, and free volume. In so doing, we seek to develop an enhanced understanding of structure-property-performance relationships in these materials that can contribute to the informed design of responsive hydrogel materials for targeted environments. This work focuses specifically on polymer compositions of 17% and 83% sodium acrylate with 0.5 and 2.0% crosslinker due to their relevance to recent research in high-performance concrete. Investigation utilizes a combination of characterization techniques that span multiple length scales in order to correlate macroscopic changes in performance with the molecular-scale interactions that induce these changes. Specifically, we incorporate bulk measurements (e.g., gravimetric swelling tests), optical analysis, and spectroscopy experiments including x-ray scattering and positron annihilation to elucidate the structural relationships between hydrogel composition (e.g., amount of charged monomer units and crosslink junctions in the network) and effects of high ionic concentrations in solution. X-ray scattering (XRD and SAXS) and positron annihilation lifetime spectroscopy (PALS) are complimentary spectroscopy techniques that allow us to probe both the size and distribution of electron-dense regions (i.e., salt crystals, collapsed polymer coils, and crosslink junctions) via x-ray scattering and the relative abundance and size of void spaces between network components (i.e., free volume) through positron annihilation. Combining these techniques with larger-scale measurements of changes in the gels’ swelling behavior, we aim to provide a complete picture of P(ANa-AM) hydrogel performance in high salinity environments.
3:45 PM - SB04.07.04
Modeling Tetra-PEG Hydrogels with Degradable Crosslinks
Vaibhav Palkar1,Chandan Choudhury1,Olga Kuksenok1
Clemson University1Show Abstract
Soft materials with controllably degradable crosslinks constitute an important component of active stimuli responsive platforms for numerous applications. As one example, fast photo-cleavage of crosslinks has enabled the development of a soft material allowing user-directed growth of neural networks. Apart from light, other stimuli such as heat and ultrasound can also be utilized for controlled degradation. Herein, we develop a Dissipative Particle Dynamics (DPD) simulation framework aimed at modeling tetra-arm polyethylene glycol (tetra-PEG) hydrogels with transient crosslinking. This framework allows single parameter control over the crosslink degradation rate. Further, we develop a correspondence of our DPD framework with continuum level modeling and isolate phantom and affine network conditions with respect to our model hydrogel network. Our results show a good correspondence with prior experimental studies on tetra-PEG gels showing crossover from phantom to affine network models for these systems with an increase in crosslink density. We then focus on adsorption of tetra-PEG nanogels at oil-water interface and on dynamics of confined films of these gels. We show that the cleavage of crosslinks leads to the controlled spreading of nanogels at the interface and to degradation-induced buckling of constrained films.
4:00 PM - SB04.07.05
Ideal Dynamic Covalent Hydrogels for Thermal Stabilization of Biologics
Bruno Marco Dufort1,Mark Tibbitt1
ETH Zürich1Show Abstract
Recent research in the design and engineering of polymer networks has introduced a new class of hydrogels based on dynamic covalent chemistry, which combines the mechanical properties of both physically and chemically cross-linked materials. Dynamic covalent hydrogels enable the formation of responsive, mouldable, and self-healing materials, as the bonds in the network can break and reform in response to external stimuli . These unique properties are being leveraged in many biomedical applications, such as in responsive drug delivery systems, dynamic scaffolds for cell culture and more recently in our work on the thermal stabilisation of biologics. The macroscale properties of these hydrogels, however, depend on the specific chemistry of the cross-link binding pairs as well as the network topology. Successful application of dynamic covalent gels therefore requires a robust understanding of how these factors influence each other and the emergent properties of the network.
In this work, we related the viscoelastic properties of dynamic covalent networks, measured by dynamic mechanical analysis, to the microscopic behaviour of the reversible junctions, through kinetic NMR studies. Boronic ester-based hydrogels were used as model dynamic covalent gels, since their viscoelastic properties can be tuned over several orders of magnitude by tailoring the chemistry of the acid-diol binding pair or by changing network pH . Oscillatory shear rheometry revealed that these materials behave as ideal dynamic covalent networks, exhibiting both rubber elastic behaviour and time-dependent mechanical properties, which can be modelled by a single Maxwell element with a spring and a dashpot in series. Uniquely, the viscoelasticity in these materials could be linked to the microscopic behaviour at the junctions via 2D 1H NMR exchange spectroscopy (EXSY), as the relaxation behaviour in these materials at different pH scale with the reaction rates of the diols with the boronic acids. This work, which links dynamics of the junction chemistry in a reversible network to its bulk behaviour, is being used to develop physical models that relate binding pair thermodynamics and kinetics to macroscale properties in order to enable the rational design of hydrogel systems.
In addition, we are applying the knowledge gained from these fundamental studies to the development of a platform material with utility in 3D printing, injectable drug delivery, and for the thermal stabilisation of biologics. We present here new results on the thermal stability of a broad range of biologics; leveraging the ability of these dynamic covalent gels to enable encapsulation, stabilisation, and triggered release of cargo. The ability to protect biologics from thermal stress with a simple material solution presents a useful approach to mitigate the cost and risk associated with reliance on a continuous cold chain for biologic transport and storage.
 B. Marco-Dufort and M. W. Tibbitt, Materials Today Chemistry, 2019, 12, 16–33.
 V. Yesilyurt et. al., Adv. Mater., 2015, 28, 86–91.
4:15 PM - SB04.07.06
Structural and Conformational Properties of Bottlebrush Polyelectrolyte Solutions
Alexandros Chremos1,Jack Douglas2,Ferenc Horkay1
National Institutes of Health1,National Institute of Standards and Technology2Show Abstract
Bottlebrush polyelectrolyte solutions have great significance in biology, e.g., aggrecan is a major proteoglycan in the articular cartilage, and exhibit great potential in drug delivery applications, however, there is little theoretical understanding of their behavior compared to their linear polyelectrolyte solutions. We made a comparative investigation of linear and bottlebrush polyelectrolyte solutions with the use of molecular dynamics simulations. In particular, we utilize a previously developed polyelectrolyte coarse-grained bead-spring model that includes an explicit treatment of the charged species and solvent to probe the conformational properties of polyelectrolyte linear and bottlebrush polyelectrolytes at different polymer and salt concentrations. Specifically, we calculate the polymer hydrodynamic radius and radius of gyration along with its eigenvalues. Moreover, we calculate the structure factor and determine the scaling of the location of the polyelectrolyte peak with polymer concentration. Overall, our findings are in agreement with small angle neutron scattering (SANS), dynamic light scattering (DLS) and osmotic pressure measurements. These complementary experimental and computational techniques probe different length and time scales providing a comprehensive picture of the essential properties of bottlebrush polyelectrolytes.
4:30 PM - SB04.07.07
Light-Induced Shape-Morphing Hydrogels—Dynamic Motion and Programmable Assembly
Hyunki Kim1,Todd Emrick1,Ryan Hayward1
University of Massachusetts Amherst1Show Abstract
Small organisms living on the surface of water often rely on the modulation of capillary forces to propel themselves on demand. For example, springtails move at the air-water interface by simply adjusting their posture, which in turn modulates capillary forces. This results in the aggregation of the springtails and migration of individuals between aggregates. Inspired by nature, we developed a dynamic soft material that mimics the behavior of on-demand attraction and repulsion and displays programmable assembly patterns and non-equilibrium capillary motion.
Our synthesis of shape-morphing hydrogels used in situ patterned growth of Au nanoparticles (NPs) embedded within temperature-responsive hydrogel films. The patterns of Au NPs yielded spatially non-uniform heating under illumination, and therefore light-induced differential swelling and wrinkling of the hydrogel films. As a result, the three-phase contact line at the air-water-hydrogel interface was distorted dynamically to generate capillary attraction and repulsion. The geometry of these hydrogel nanocomposite films was designed to generate specific wrinkling patterns and resulting configurations of the hydrogel assemblies. Time-varying patterns of illumination led to reconfiguration of the assemblies, allowing them to be ‘annealed’ to reach low-energy structures. Furthermore, an appropriately chosen static pattern of illumination and geometry of the hydrogel actuator induced sustained rotation and translation. This approach provides synthetic tools to control objects in time and space with implications for the design of hydrogel nanocomposite materials and soft robots.
 Hyunki Kim, Ji-Hwan Kang, Ying Zhou, Alexa S. Kuenstler, Yongjin Kim, Chao Chen, Todd Emrick*, Ryan C. Hayward*, Light-driven shape morphing, assembly and motion of nanocomposite gel surfers, Advanced Materials, 1900932 (2019).
4:45 PM - SB04.07.08
Muscle-Like Fatigue-ResistantHydrogels by Mechanical Training
Shaoting Lin2,Ji Liu1,2,Xinyue Liu2,Xuanhe Zhao2
Southern University of Science and Technology1,Massachusetts Institute of Technology2Show Abstract
Skeletal muscles possess the combinational properties of high fatigue resistances (1,000 J/m2), high strengths (1 MPa), low Young’s moduli (100 kPa), and high water contents (70 − 80 wt%), which have not been achieved in synthetic hydrogels. The muscle-like properties are highly desirable for hydrogels’ nascent applications in load-bearing artificial tissues and soft devices. Here, we propose a strategy of mechanical training to achieve the aligned nanofibrillar architectures of skeletal muscles in synthetic hydrogels, resulting in the combinational muscle-like properties for the first time.1 These properties are obtained through the training-induced alignment of nanofibrils, without additional chemical modifications or additives. In situconfocal microscopy of the hydrogels' fracturing processes reveals that the fatigue resistance results from the crack pinning by the aligned nanofibrils, which require much higher energy to fracture than the amorphous polymer chains. This strategy is particularly applicable for three-dimensionally printed microstructures of hydrogels, in which we can achieve isotropically fatigue-resistant, strong yet compliant properties.
1. S. Lin,† J. Liu,† X. Liu, X. Zhao. Proc. Natl. Acad. Sci., 2019, 16, 10244-10249.
SB04.08: Poster Session II: Hydrogel II
Marc In het Panhuis
Wednesday PM, December 04, 2019
Hynes, Level 1, Hall B
8:00 PM - SB04.08.01
Synthesis of Photo-Activating Acryl-Polyurethane Containing Multifunctional Monomer for High Strength and Biocompatible 3D Printing Materials
PilHo Huh1,Jihong Bae1
Pusan National University1Show Abstract
A UV curable acryl-polyurethane is successfully prepared by a combination of poly(tetramethylene ether) glycol (PTMG) and 1,4-butanediol (1,4-BD) as polyols, 4,4’-methylene bis(phenylisocyanate) (MDI) as an isocyanate, pentaerythritol triacrylate and triethyleneglycol dimethacrylate (TEGDMA) as multifunctional monomers and benzophenone was used to photoinitiator for UV curing to optimize the physical property of the 3D structure. The crosslinking step of acryl-polyurethane elastomers were processed using the exposure to 385~405nm UV radiation. The structure of the resulting acryl-polyurethane was evaluated by fourier transform infrared spectroscopy (FT-IR), gel permeation chromatography (GPC). The tunable UV absorbance of acryl-polyurethane was adjusted through the material design. The mechanical properties such as tensile strength, elongation and modulus were evaluated by universal testing machine. And flexural strength and hardness were measured by durometer and ISO test machine. The surface resolution-quality of the 3D structure was analyzed by field emission scanning electron microscope (FESEM).
8:00 PM - SB04.08.02
Stability-Enhanced Chitosan-Catechol 3D Bioink by Diatom Frustule Silica
Jeehee Lee1,Haeshin Lee1
Korea Advanced Institute of Science and Technology1Show Abstract
This study shows the availability of a 3D bioink enhanced by diatom frustules. Diatoms are photosynthetic, aquatic creatures with a skeleton called frustule, mainly composed of silica.
Many materials for 3D printing require a liquid to solid transition so that stimuli such as temperature, or UV curing were employed. However, this method is difficult to use in bio printing, which requires printing with live cells. Although there are many conventional biocompatible materials, it should be fulfill requirements: injectable, adhesive to the each layer, and maintainable without spreading after printing.
Chitosan-catechol, mussel-inspired adhesive, is a 3D bioink that catechol is conjugated to chitosan, which contains an amine group that plays a synergistic role in adhesion with catechol. Chitosan-catechol is the representative adhesive that best mimics the adhesion of mussel byssus. Rapid complex formation of chitosan catechol with serum proteins is known to be able to form 3D structures. Thus, it is also possible to use it as a bio ink for rapid liquid printing, which is next generation 3D printing, not to be stacked layer by layer. However, while having a good system, the formed chitosan-catechol 3D composites have poor stability after injection and weak mechanical strength after gelation. There have been attempts to overcome this with addition of vanadium, but there are still other issues to address such as in terms of price and in vivo safety as well as performance.
In this study, we significantly enhanced the stability of the bio ink by simply mixing silica microparticles with a charged nanoporous structure. As a model system, we used Melosira nummuloides, because they are relatively bulky at ~ 50 μm in diameter, and numerous nanopores are exposed to the surface, which is likely to increase the chance to form entanglements of the bio-ink polymer to the silica surface. The results showed that the addition of Melosira nummuloides greatly increased the post - injection stability of chitosan-catechol bioink, and confirmed increased storage and loss modulus values and shear thinning rheological properties. Through the Universal Testing Machine data, it was confirmed that it has stronger mechanical tensile strength. In addition, it is verified that cells were viable on this bio ink. By using these properties, it is possible that diatom frustule-reinforced chitosan-catechol bioink can be used for printing directly in the body.
8:00 PM - SB04.08.04
Static and Dynamic Properties of Aggrecan Assemblies
Ferenc Horkay1,Peter Basser1,Erik Geissler2,Anne-Marie Hecht2
National Institutes of Health1,Universite Grenoble Alpes2Show Abstract
Aggrecan is a bottlebrush shaped high molecular weight proteoglycan. It consists of an extended protein core to which many chondroitin sulfate and keratan sulfate (linear sulfated polysaccharide) chains are attached. This array forms a bottlebrush structure. Aggrecan’s primary biological role is to provide the osmotic properties for cartilage. In the presence of hyaluronic acid (HA) aggrecan molecules self-assemble into a supramolecular structure with as many as 100 macromonomers bound to a HA molecule. The aggrecan-HA complexes govern the load bearing properties of cartilage.
Small angle neutron scattering (SANS), dynamic light scattering (DLS) and osmotic pressure measurements were made on near physiological solutions of aggrecan and aggrecan-HA complexes. SANS reveals that the supramolecular structure of aggrecan assemblies is only marginally affected by the HA molecules. DLS indicates that the dynamic response of the aggrecan-HA complex is slower than that of the corresponding aggrecan solution. The relaxation rates measured by dynamic light scattering is proportional to q3, which is the signature of internal modes in large loosely connected assemblies of smaller units, such as individual aggrecan molecules. This is reflected in the hydrodynamic radius, RH, whose apparent value varies inversely with q. With increasing aggrecan concentration RH increases, which is a consequence of the steric hindrance due to densification of the aggrecan aggregates. HA slows the relaxation rate in agreement with an increase of the friction coefficient owing to the rearrangement of the aggrecan molecules along the HA chain. However, addition of calcium chloride slightly increases the relaxation rate of the correlation function. Osmotic pressure measurements quantify the effects of HA and calcium chloride on the osmotic modulus, which defines the compressive resistance of aggrecan assemblies.
8:00 PM - SB04.08.08
Decellularized Extracellular Matrix for In Situ Cell Encapsulation for Tissue Engineering
Seth Edwards1,Jason Brown1,Kyung Jae Jeong1
University of New Hampshire1Show Abstract
Extracellular matrix (ECM) provides the ideal microenvironment for various tissue specific cellular functions including adhesion, migration, proliferation and differentiation. Using decellularized ECM (D-ECM) as a tissue engineering scaffold has been proposed proposed to take advantage of the chemical and physical information it retains for the growth of tissue-specific cells, in addition to retention of physical strength of the original tissue. However, introduction of cellular components into D-ECM scaffolds involves injection of cells, significantly damaging the D-ECM structure and resulting in a poor distribution of cells within the ECM. Thus, scaffolds of this nature are unfit for traditional cellular encapsulation. Alternatively, D-ECM can be milled and digested into a solution, and crosslinked to form a homogeneous hydrogel. Although this method enables in situcell encapsulation, the mechanical properties of the resulting hydrogel are poor due to the low concentration of soluble D-ECM (~ 2%), and encapsulated cells are trapped in the polymer mesh of the hydrogel, which inhibits cell adhesion, spreading, and proliferation. In addition, the digestion of D-ECM results in a partial loss of molecules important to ECM function, anddestroys the 3D microenvironment of the original ECM, which has been shown to be important in promoting proper cell and tissue function. Here, we propose a new method of producing D-ECM hydrogel, by assembling and curing D-ECM ‘microparticles’, allowing for in situcell encapsulation. Using porcine corneal stroma as a model tissue, D-ECM is first mechanically milled into microparticles by cryomilling, and upon suspension in physiological buffer, particles are chemically crosslinked by microbial transglutaminase (mTG). Due to a high solids concentration, the resulting hydrogel has improved mechanical strength when compared to homogeneous D-ECM hydrogel. Additionally, the macroporous structure allows for a more optimal growing surface for encapsulated cells when compared to homogeneous D-ECM hydrogel, and the negation of a digestion step allows for the partial retention of the original ECM microstructure. This proposed change in methodology introduces a new avenue of research for using D-ECM as a biomimetic scaffold, and can be applied to other relevant tissues.
8:00 PM - SB04.08.09
Design of Dual Stimuli-Responsive Bio-Actuator Using Integrated Modeling and Genetically Engineered Silk-Elastin-Like-Proteins
The Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University1,The 2nd Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University2Show Abstract
Fine-turned programmable shape changing biomaterials are crucial for a variety of task-specific applications ranging from health care to sustainable novel devices. Biocompatible smart actuators with multifunctions and complicated architectures fabricated from natural materials remains a challenge. To generate tailored bio-polymeric materials with predictive functional outcomes, exploiting designs from nature while morphing them towards non-natural systems offers an important strategy.
Elastin is a major structural protein abundant in the extracellular matrix, providing reversible extensibility and elastic recoil to the skin, elastic cartilage and blood vessels. The dynamic elastomeric systems based on elastin proteins have gained increasing attention due to their great potential for controlled release and actuating systems. In current research, an integrated modeling-experimental approach were used to rationally design and fabricate stimuli responsive and shape changing silk-elastin-like protein (SELP) hydrogels, which response to environmental stimuli, such as thermal, pH and enzymatic triggers. New stimuli-responsive bilayer hydrogel actuators were also fabricated based on genetically engineered SELP in composite laminate arrangements with cellulose nanofibers (CNF). These hybrid devices were designed to respond to dual stimuli, temperature and ionic strength, around body temperature and salt concentration of 0.5 Mm to 5 M. The sensitivity of these actuators support intricate morphological transformations in SELP/CNF bilayer designs where pre-patterned control of the materials assembly provides options for diverse applications for these devices. These studies provided further insight into the sequence-function relationship of SELP and bio-actuator design, and therefore accelerated the development of stimuli-responsive biomaterials.
8:00 PM - SB04.08.11
Rationally Designed Self-Healable Planar Supercapacitor for Driving an Integrated UV/NO2 Multifunctional Sesnor
Minsu Kim1,Jeong Sook Ha2,1
KU-KIST graduate school1,Korea University2Show Abstract
Recently, there have been extensive efforts to develop self-healable electronics with reliability which can spontaneously restore electrochemical as well as mechanical properties after damages due to external impact or continuous usage. In this work, we report a rationally designed self-healable planar sueprcapacitor for driving an integrated UV/NO2 multifunctional sensor. As a good self-healable electrolyte in both air-ambient and watery conditions, PVA/Borax/Agarose hydrogel with NaNO3 was used. The dynamic network of PVA−Borate provides the hydrogel with ultrafast self-healing property, and the agarose network provides an additional mechnical strength and stability. Bisected hydrogel electrolyte restores 96% of tensile stress and 98% of ionic conductivity after simple physical contact for 30 s without external stimuli. Gold nanosheets and multi-walled carbon nanotubes (MWNTs) transferred on to a PVA/Agarose substrate by vacuum filtration was used as self-healing electrodes. A multifunctional sensor was fabricated by vacuum filtration of MWNTs and Zinc oxide nanowires to detect both UV and NO2. The fabricated self-healable supercapacitor exhibits areal capacitance of 68.7 mF cm-2 at 1 mA cm-2, maximum energy density of 6.1 μWh cm-2, and maximum power density of 1.4 mW cm-2. The supercapacitor maintained 87% of initial capacitance and the UV/NO2 sensor also kept its sensing ability after 5 repetitive healing cycles. Using the stored energy of the supercapacitor, both UV and 10 ppm of NO2 gas could be detected for sufficiently long time. This work demonstrates a high potential of our self-healable planar supercapacitor as an integrated energy storage device in application to high performance self- healable sensor system.
8:00 PM - SB04.08.13
3D Printing of Anisotropic Hydrogels with Bioinspired Motion
Hakan Arslan1,Amirali Nojoomi1,Junha Jeon1,Kyungsuk Yum1
University of Texas1Show Abstract
Motion in biological organisms often relies on the functional arrangement of anisotropic tissues that linearly expand and contract in response to external signals. However, a general approach that can implement such anisotropic behavior into synthetic soft materials and thereby produce complex motions seen in biological organisms remains a challenge. Here, we present a bioinspired approach that uses temperature-responsive linear hydrogel actuators, analogous to biological linear contractile elements, as building blocks to create three-dimensional (3D) structures with programmed motions. This approach relies on a generalizable 3D printing method for building 3D structures of hydrogels using a fugitive carrier with shear-thinning properties. This study demonstrates that the metric incompatibility of an orthogonally growing bilayer structure induces a saddle-like shape change, which can be further exploited to produce various bioinspired motions from bending to twisting. The orthogonally growing bilayer structure undergoes a transition from a stretching-dominated motion to a bending-dominated motion during its shape transformation. The modular nature of this approach, together with the flexibility of additive manufacturing, enables the fabrication of multimodular 3D structures with complex motions through the assembly of multiple functional components, which in turn consist of simple linear contractile elements.
8:00 PM - SB04.08.14
Molecular Dynamics Simulations of Nanocomposite Hydrogels with Nanoplatelet Clay Fillers
Shoumik Saha1,Miriam Rafailovich1,Dilip Gersappe1
SUNY-Stony Brook1Show Abstract
Nanocomposite hydrogels are physical gels formed from a mixture of hydrophilic polymer chains and nanoparticles. They have enhanced properties and can retain higher amounts of water. Despite the large number of experimental studies on this topic, little is known about the mechanism of formation and structure of these gels. Here, we use molecular dynamics simulations to study structure formation in physically associating nanocomposite hydrogels. Nanofillers were modeled as rigid bodies of disk-like shapes and physical crosslinks were simulated by introducing a short-range attraction between the nanofillers and polymer chain ends. The structure, dynamics and mechanics of these polymer gels were studied as a function of nanofiller volume fraction. We model gels both with a single polymer, as well as a binary mixture of polymers to study the effects of polymer chain interaction and assembly on structure formation and gelation of these systems. Our results show that assembly between the nanoparticles is an important determinant of the final properties of the gel. This assembly is mediated by the types and interactions of the polymer used. Our simulations are able to determine local structural information and can determine conditions under which the strength of the hydrogel is optimal.
8:00 PM - SB04.08.15
Systematic Characterization of 3D-Printed Polycaprolactone/ Poly (Ethylene Oxide)/ Hydroxyapatite (HA) Scaffolds For Biomedical Devices and Bone Tissue Engineering—Influence of Material Composition and Structure Design
Roger Narayan2,Bin Zhang1,2,Alesander Nguyen2,Jie Huang1
University College London1,University of North Carolina at Chapel Hill and North Carolina State University2Show Abstract
This works aims at guiding systematic experimental characterization for the design of 3D printed scaffolds for bone tissue applications, focusing on direct ink writing with a biocomposite of polycaprolactone (PCL), poly (ethylene oxide) (PEO) and hydroxyapatite (HA). Firstly, the effect of the material composition (HA concentration in the range from 55 to 85% w/w) on the PCL/PEO/HA ink rheology properties we studied. Secondly, the impact of the ink compositions on the 3D printed scaffold mechanical properties were systematically investigated. Thirdly, different concentrations of vancomycin drug (5%, 10%, and 15% w/w) have been successfully loaded on the PCL/PEO/HA scaffold, and drug release profile was investigated. Work is continuing to characterize the PCL/PEO/HA scaffolds in anti-microbial properties and tissue regeneration in biological models to develop a 3D multifunctional composite scaffolds by changing scaffold material, structures, and mechanical properties. The biocomposite scaffold fabricated in this study has the potential for the application of tissue replacement.
8:00 PM - SB04.08.16
Additive Manufacturing of Bovine Serum Albumin-Based Hydrogels and Bioplastics
Patrick Smith1,Benjaporn Narupai1,Jonathan Tsui1,Sayami Millik1,Ryan Shafranek1,Deok-Ho Kim1,Alshakim Nelson1
University of Washington1Show Abstract
Bio-sourced and biodegradable polymers for additive manufacturing could enable the rapid fabrication of parts for a broad spectrum of applications ranging from healthcare to aerospace. However, a limited number of these materials are suitable for vat photopolymerization processes. Herein, we report a two-step additive manufacturing process to fabricate robust protein-based constructs using a commercially available laser-based SLA printer. Methacrylated bovine serum albumin (MA-BSA) was synthesized and formulated into aqueous resins that were used to print complex 3D objects with a resolution comparable to a commercially available resin. The MA-BSA resins were characterized by rheometry to determine the viscosity and the cure rate, as both of these parameters can ultimately be used to predict the printability of the resin. In the first step of patterning these materials, the MA-BSA resin was 3D printed, and in the second step, the printed construct was thermally cured to denature the globular protein and increase the intermolecular noncovalent interactions. Thus, the final 3D printed part was comprised of both chemical and physical cross-links. Compression studies of hydrated and dehydrated constructs demonstrated a broad range of compressive strengths and Young’s moduli that could be further modulated by adjusting the type and amount of co-monomer. The printed hydrogel constructs demonstrated good cell viability (> 95%) after a 21-day culture period. These MA-BSA resins are expected to be compatible with other vat photopolymerization techniques including digital light projection (DLP) and continuous liquid interface production (CLIP).
8:00 PM - SB04.08.18
Optimizing Thermal and Mechanical Properties of Poly(Lactic Acid) / Polypropylene / Graphene Nanocomposite Polymer Blends in Fused Deposition Modeling Systems
Yu-Chung Lin1,Larry Huang2,Richard Li3,Addison Liu4,Nikita Salunke5,Yuval Shmueli1,Miriam Rafailovich1,Steve Nitodas1
Stony Brook University, The State University of New York1,Wilton High School2,Conestoga High School3,Unionville High School4,Evergreen Valley High School5Show Abstract
The Fused deposition modeling (FDM) process is highly non-equilibrated and often has inadequate thermal retention, posing problems which can be addressed via binary blending. This work explores a binary polymer blend of polylactic acid (PLA) and isotactic polypropylene (iPP) with added graphene nanoplatelets (GNPs). Mechanical testing revealed that in comparison to a control sample of pure PLA, the addition of only 1% iPP resulted in a 66% increase in toughness, and a further increase to 2.5% resulted in an increase of only 16%. Further increase above 5% decreased the toughness by 45%. These results correlated with SEM and HD optical microscopy where the filament/filament interfaces were still visible in the pure PLA sample, while they appeared completely fused in the sample with 1% iPP. Water contact angle goniometry showed an increase from 66 degrees on the pure PLA sample to 88 degrees, the value of pure iPP, on the samples containing only 1% iPP. These results indicate that an iPP shell had formed at the filament surface, which is consistent with the segregation of iPP whose surface tension is significantly lower than that of PLA. The glass transition of iPP, also being lower than that of PLA, enables interdiffusion between filaments, leading to complete obliteration of the interface and enhanced mechanical properties. Blends of iPP/PLA containing 5% GNPs were also produced and drawn into filaments. While SEM imaging indicated nearly complete alignment of the GNPs along the extrusion direction, partial sequestration of the particles in the iPP shell and internal phase segregated regions were also evident. Infrared imaging (FLIR A300) of samples in contact with a well-defined heat flux indicated an increase of 159% over the pure PLA control sample with the addition of 5% GNP. Addition of 5% GNP, with 2.5% and 5% iPP yielded an increase of 272% and 245% respectively, indicating greater thermal conduction efficiency when graphene platelets are confined in the iPP domains.
8:00 PM - SB04.08.19
Thermoresponsive Triblock Copolymers for 3D Printing of Hydrogels
Jinhwan Yoon1,Kusuma Betha Cahaya Imani1
Pusan National University1Show Abstract
Pluronic is a highly biocompatible and thermoresponsive triblock copolymer consists of hydrophobic poly(propylene oxide) (PPO) as the center block and hydrophilic poly(ethylene oxide) (PEO) as the side bocks. Because of its amphiphilic nature, pluronic possess the ability to form spherical micelles within aqueous solution above its critical micelle temperature (CMT). This phenomenon is driven by the decrease of PPO block’s solubility, forming a core for the miscelles. This reverse thermoresponsive characteristic allows pluronic to have shear thinning property, which can be utilized as an ink for extrusion 3D printing. The quick shear thinning behavior is useful to prevent the ink from flowing upon its deposition on a substrate and retain the desired shape. In this study, we combined pluronic F127 ((PEO)99-(PPO)65-(PEO)99) with methacrylate groups into pluronic F-dimethacrylate (FDMA) as an ink to prepare hydrogels with extrusion-based 3D printing. The methacrylate groups are added to maintain the 3D printed structure after immersion in water by photopolymerization, forming crosslinking that prevent pluronic from dissolving out. In addition, we also manipulated the hydrogels toughness and conductivity by incorporation of ionic bonding and conductive materials. The synthesis of FDMA is simple and it has the prospect for further studies in various fields such as soft robotics and tissue engineering as artificial human organs.
8:00 PM - SB04.08.20
Toughening of Polysaccharide Hydrogels for Biomedical Applications
Muhammad Hossen1,Michael Mason1
University of Maine1Show Abstract
Polysaccharide hydrogels are excellent candidates for biomedical applications such as drug delivery, wound dressing and tissue engineering. For each of these applications, mechanical robustness of the gels, specifically in an aqueous environment, is crucial. Polysaccharide gels are commonly formed by fiber entanglement and hydrogen bonding. Water molecules can disrupt the hydrogen bonding and causes disentanglement of the fibers. Therefore, these gels lose their stiffness and structural integrity in water. Here we describe a new approach for generating wet stable and mechanically stiff semi-interpenetrating (IPN) composite hydrogels through the addition and photo-crosslinking of methacrylate functionalized carboxymethyl cellulose (MetCMC) in the polysaccharide matrices. Physical and mechanical properties such as wet stability, swelling, shrinkage, and stiffness of the gels were studied to test their suitability towards biomedical applications. Data supporting the superior mechanical properties and biocompatibility of the chemically cross-linked wet stable polysaccharide hydrogels will be presented.
8:00 PM - SB04.08.21
Poly(ethylene glycol) diacrylate (PEGDA) Degradation Studies for Tissue Engineering Applications
Deldrys Gomez Reynoso1,Ozlem Yasar1
City University of New York1Show Abstract
Tissue engineering targets to study the organ regeneration as an alternative approach to the organ transportation. Organ regeneration can only be done successfully, if cells are seeded on the building blocks that are known as scaffolds. Scaffolds help cells to grow in 3-D, as cells migrate within the scaffolds.In this research, Poly(ethylene glycol) diacrylate (PEGDA) was chosen to fabricate the engineered scaffolds. PEGDA is a phot-curable solution and it can be mixed with different chemical solutions to work with the different percentages of PEGDA. In this research, degradation rate of PEGDA was studied. First of all, three sets of cylindrical PEGDA samples with the height of 14 mm and diameter of 14 mm were fabricated by using the 20%, 40%, 60%, 80% and 100% of PEGDA. All of the cylindrical samples were weighted before the degradation tests. Then, first PEGDA sets were immersed into the limonene solution for four hours and they were weighted in every hour. Their dimensions were also measured in every hour. After that, the second set of PEGDA samples were immersed into the water and both weight and dimension measurements were also done in every hour for four hours. At the end, the third PEGDA samples were immersed into the 99% ethyl alcohol and their weight and dimensions were measured in every hour. Our results indicate that, as the PEGDA percentage increases, its degradation rate decreases. Also, PEGDA degrades away the most in the 99% ethyl alcohol more than limonene and water. Our research to study the degradation rate of PEGDA will extend to the use of hot-stir plate to study investigate the temperature affect.
8:00 PM - SB04.08.22
Designing of Three-Dimensional Hybrid Scaffolds for Tissue Regeneration
Olga Urbanek-Swiderska1,Dorota Kolbuk1
Institute of Fundamental Technological Research PAS1Show Abstract
Application of electrospun nonwovens is limited due to its two-dimensional (2D) architecture. Hybrid scaffolds consisting of electrospun fibres and other 3D techniques are formed to overcome this problem. Those scaffolds are able to combine advantages of both materials’ forms . Electrospun nanofibers mimic the biopolymer network of native tissue very well and provide significant surface area for attaching bioactive components for local stimulation of cellular activity. On the other hand, hydrogels and its freeze-dried forms provide 3D architecture. An example of 3D tissue are bones cavities, occurring in the result of disease or injuries. For this purpose fibres may be coated with hydroxyapatite, in order to stimulate osteoblasts proliferation and activity .
The aim of this research was to develop 3D hybrid scaffold from the electrospun fibres and hydrogel. Poly(lacide-co-glicolide)(PLGA) fibres were formed via electrospinning technique and subjected to ultrasounds in order to increase the nonwoven dimensions. Additionally, this procedure was used to cover one group of the nonwovens with hydroxyapatite (nHAp). Finally, fibres were immersed in gelatine solution, crosslinked and subjected to both, materials characteristic and in vitro biological tests.
The contribution of fibres to hydrogel mass after lyophilisation was 50/50 w/w. SEM imaging confirmed presence and homogenously distributed PLGA and PLGA-nHAp coated fibres in the pore walls. FTIR, EDS analysis as well as WAXS measurement confirmed presence of nHAp crystal in the scaffolds, its distribution and structure. DSC analysis revealed no significant changes in glass transition temperature nor melting temperature of PLGA. The weight loss of 3D scaffolds was conducted per one month. During the first week of incubation the weight loss was ca. 5%. Moreover, the mechanical tests and in vitro tests were conducted. The biological tests confirmed constant proliferation of cells in the analysed time points, as well as proper cell morphology and spreading on the scaffold surface.
Summarizing, presented technique is an effective method of 3D hybrid scaffolds preparation, based on ECM mimicking electrospun fibres.
Acknowledgments: This work was supported by the National Centre of Research and Development within the grant No. 388/L-6/2014.
References:  Bosworth, L. A. et. al. Nanomedicine: Nanotechnology, Biology and Medicine 2013, 9(3), 322-335.  Kolbuk, D. et al. Journal of Biomedical Materials Research Part A 2019.
8:00 PM - SB04.08.23
3D Printed Cochlea Models for Cochlear Implant Studies
Iek Man Lei1,Chen Jiang1,Manohar Bance1,Yan Yan Shery Huang1
University of Cambridge1Show Abstract
Since the mid-1980s, cochlear implants have been used to treat severe hearing loss, remarkably improving patients’ quality of life. Despite its successful clinical translation, several issues of the current cochlear implants remain. These are such as the frequency distortion problem caused by the current spread within cochlea, and the enormous individual differences in the treatment outcomes. Animal models have been extensively used in the pre-clinical research, however these models fail to demonstrate the anatomical features and the individual variability of human cochlea. In an effort to reduce in vivo approaches and to develop a personalised model for cochlear implant testing, this work aims to develop a 3D printed cochlea model for cochlear implant research. Here, we demonstrate a novel strategy to fabricate a cochlea model by embedded 3D printing. Our 3D model was designed to replicate the key anatomical features of the human cochlea; the composition of the gel matrix was tuned to match the impedance properties of temporal bone. We showed that the Electric Field Imaging (EFI) profiles obtained from the 3D printed models are highly similar to the clinical patients’ profiles. These 3D cochlear models see the potential to be used as a tool to understanding the clinical outcome of existing cochlear implantation; or as a pre-clinical model for testing new cochlear implants.
8:00 PM - SB04.08.25
White Light Emitting Graphene Quantum Dot Hydrogels for Bioimaging and Biosensing Applications
Ankarao Kalluri1,Bilal Cakir2,Prabir Patra3,In-Hyun Park2,Challa Kumar1
University of Connecticut1,Yale University2,University of Bridgeport3Show Abstract
A new facile synthesis of white light-emitting, multifunctional, water-soluble, metal-free, non-toxic, highly photostable, bio-active Protein Quantum dot (ProQDot) hydrogels is reported here. These advanced functional nanoparticles consist of cross-linked bovine serum albumin (BSA) and graphene quantum dots (GQDs). The ProQDots contain blue, green and red dye conjugated GQDs, which are intern crosslinked with BSA to form white emitting hydrogels. These are bio-degradable and highly photostable when compared to organic and inorganic dyes. This bio-hydrogels are further characterized by XRD, CD, FT-IR, DLS, Raman, UV-Visible, TEM, SEM, confocal laser microscopy, photoluminescence spectroscopy, and gel electrophoresis techniques. This robust ProQDots with a variety of surface-functionalities with unique optical properties has led to promising applications in bioimaging, cellular biology, and drug delivery studies. Furthermore, as prepared ProQDot hydrogels can be used to study neuronal intracellular processes for in vivo observation of cell trafficking, tumor targeting, bio-sensing, CRISPR-Cas, and immunohistochemistry (IHC) applications.
8:00 PM - SB04.08.26
Biorprinting Autologous Dermal Equivalent Organotypics
Saba Gulzar4,Juyi Li1,Michael Cottone1,Philip Cottone1,Olias Christie1,Vivian Su1,Zahin Huq1,Michael Gozelski1,Sampson Berlinski1,Kimberly Lu1,Adeel Azim1,Christopher Chan2,Teresa Duong3,Clara Dokyung Lee5,Stella Lessler6,Somya Mehta2,Katherine Tian7,Marcia Simon1,Miriam Rafailovich1
Stony Brook University, The State University of New York1,Hicksville High School2,St. Anthony’s High School3,New Hyde Park Memorial High School4,Daegu International School5,Yeshivah of Flatbush Joel Braverman High School6,Ward Melville High School7Show Abstract
Rheinwald and Green were pioneers in the development of cell culture methods later incorporated into the protocol for production of organotypic cultures. The technique, as described by , dermal fibroblasts are first spread as sheets encapsulated in a collagen matrix, then keratinocytes, expanded using immortalized 3T3 cells are spread on top at a high density. This technique proved very successful since it used autologous cells to minimize rejection, and the use of 3T3 cells allowed for rapid expansion of epithelial cells. In order to further increase the utility of these dermal equivalents, inclusion of vascularization is desirable. Production of the organotypics via bioprinting would greatly facilitate attainment of this goal, since the flat sheets could be replaced by patterned layers where vascularization could be initiated through insertion of angiogenic hydrogel segments. Here we first report on the production of the autologous organotypic following the protocol of Carlson  adapted for printing with a Cell Ink bioprinter. The first layer of fibroblasts embedded in collagen and second layer of keratinocytes were either printed with a 0.2mm nozzle or simply poured to make four different conditions of skin equivalents. The organotypics were evaluated by H&E staining and compared with those produced by the standard sheet deposition method. The results indicated that even though the structures had high integrity and good interlayer adhesion, the keratinocytes layer was significantly thinner in the printed samples. Ancillary experiments to determine the effect of nozzle shear showed no influence on the ability of fibroblasts to contract collagen, but a small yet significant reduction in colony formation by the keratinocytes was observed. Further testing will be performed to determine if this is a consequence of the larger keratinocyte cell printing density or the lower viscosity of printing solution. Overlaying the secondary pattern structures for vascular initiation may induce further shear, and the impact on the skin structures will be presented.
Carlson, Mark W., et al. "Three dimensional tissue models of normal and diseased skin." Current protocols in cell biology 41.1 (2008): 19-9.
8:00 PM - SB04.08.27
In Situ Simultaneous Time Resolved X-Ray Scattering and Thermal Imaging and of Isotactic Polypropylene Homopolymer and Graphene Nanocomposites During Fused Filament Deposition Printing
Yu-Chung Lin1,Miriam Rafailovich1,Yuval Shmueli1,Sungsik Lee2,Mikhail Zherenkov3,Rina Tannenbaum1,Dilip Gersappe1,Gad Marom4
Stony Brook University, The State University of New York1,Argonne National Laboratory2,Brookhaven National Laboratory3,The Hebrew University of Jerusalem4Show Abstract
Fused filament deposition (FDM) is a common 3D printing technique, in which a thermoplastic polymer is melted and extruded in specific forms according to the user input file. In contrast to bulk fabrication methods, the FDM printing occurs under conditions which are far from equilibrium, and produce rapidly fluctuating thermal and mechanical gradients, which have temporal as well as spatial variations that can impact crystallization and ultimately filament fusion and sample integrity. In order to image these gradients directly, and understand the structure property relationships during the FDM process, we have designed an apparatus which can be placed directly in an X-ray scattering beamline to simultaneously profile, with micron spatial resolution, temperature, and SAXS, MAXS and WAXS spectra. Here we describe results obtained with isotactic polypropylene (iPP) and iPP/graphene nanocomposite filaments. The homopolymer filaments were amorphous when they emerged from the nozzle, but crystallization, of a shish-kebab structure occurred within 12 seconds initially at the outer edge of the filament (shell) and propagating in time towards the center. When the second filament was printed, the core continued to crystalize, but crystallinity in the shell disappeared, which was attributed to chain relaxation to relieve stress across the interfacial region. Three-point-bending measurements of the flexural modulii showed no significant difference between molded and printed samples, consistent with SEM images which showed complete internal fusion of the filaments. The shish kebab structures were not present when more than 1% GNPs were included. Orientation of the graphene along the flow direction as well as redistribution of the platelets towards the center of the filament were observed, which correlated with large directional enhancement of the thermal and electrical conductivities of the printed samples. The depletion of GNP from the shell region correlated with SEM images of cryo-fractured segments. The enhanced thermal retention in this region enabled chain diffusion across the filament interfaces, consistent with the good mechanical performance of the composites.
8:00 PM - SB04.08.28
Enhancing the Flame Retardancy of Biodegradable Poly(vinyl alcohol) Hydrogels with Resorcinol Bis(diphenyl phosphate) Coated Starch
Jalaj Mehta2,Yuan Xue1,Lauren Stiefel3,Miriam Rafailovich1
Stony Brook University1,Hauppauge High School2,Yeshiva University High School for Girls3Show Abstract
Flame retardant components are necessities to a firefighter‘s protective gear, such that more eco-friendly advancements in this technology have become more pertinent in an effort to better ensure the safety of both firefighters and victims in fire. Conventionally, flame retardants have been created from only slightly biodegradable superabsorbent polymers with extremely high water content. Generally these superabsorbent polymers are derived from acrylic acid and acrylamide and unless these are oligomers it is likely that they are not biodegradable. In lou of these facts the primary goal of this research was to synthesize a biodegradable hydrogel flame retardant that is as efficient as its less environmentally friendly equivalents.
To create the hydrogel samples we used a cyclic freezing and defrosting procedure consisting of 24 hours in a -20 degree Celsius freezer and then 1 hour of defrosting at room temperature 3 times for each set of samples. We derived from the FTIR results that hydrogen bonds were present in the PVA and RDP-PVA, and learned that the gels were mainly shear-thinning through the rheological studies. Overall samples with PVA as the hydrogel base with RDP-coated starch performed the best in terms of the completeness of the char layer formed. The temperature of the skin sample under the hydrogel were kept being below 65°C durning burning test. Additionally the flame retardant hydrogel displayed clear shear-thinning. Thermal protective performance (TPP) tests were performed to evaluate heat transmission through the FR hydrogel when exposed to a continuous heat source, and result compared to the Stoll Curve which represent the heat level for causing second-degree burn. The TPP test result showed that the poly(vinyl alcohol) flame retardant hydrogel provided a prolonged protection time.
Marc In het Panhuis, University of Wollongong
Namita Choudhury, RMIT University
Ferenc Horkay, National Institutes of Health
Jurgen Groll, University of Wurzburg
Marc In het Panhuis
Thursday AM, December 05, 2019
Hynes, Level 3, Room 302
8:00 AM - *SB04.09.01
Photo-Crosslinkable Hydrogel Platform for Tailored Scaffold Design
Sandra Van Vlierberghe1,Jasper Van Hoorick1,2,Liesbeth Tytgat1,2,Lana Van Damme1,3,Aysu Arslan1,Peter Gruber4,5,Marica Markovic4,5,Aleks Ovsianikov4,5,Heidi Declercq3,Peter Dubruel1
Ghent University1,Vrije Universiteit Brussel2,University Hospital Ghent3,Vienna University of Technology (TU Wien)4,Austrian Cluster for Tissue Regeneration5Show Abstract
Biofabrication is a specific area within the field of tissue engineering which takes advantage of rapid manufacturing (RM) techniques to generate 3D structures which mimic the natural extracellular matrix (ECM). A popular material in this respect is gelatin, as it is a cost-effective collagen derivative, which is the major constituent of the natural ECM. The material is characterized by an upper critical solution temperature making the material soluble at physiological conditions. To tackle this problem, the present work focusses on different gelatin functionalization strategies which enable covalent stabilization of 3D gelatin structures [1, 2].
In a second part, synthetic (multifunctional) acrylate-endcapped, urethane-based precursors will be discussed with exceptional solid state crosslinking behaviour compared to conventional hydrogels .
Several polymer processing techniques will be covered including conventional 3D printing using the Bioscaffolder 3.1, two-photon polymerization (see Fig.) and electrospinning starting from crosslinkable hydrogels. A number of biomedical applications will be tackled including adipose tissue engineering , vascularization , ocular applications , etc. The results show that chemistry is a valuable tool to tailor the properties of hydrogels towards processing while preserving the material biocompatibility.
References :  J. Van Hoorick et al., Macromolecular Rapid Communications (2018) 39 : 1800181, doi: 10.1002/marc.201800181.  J. Van Hoorick et al., Biomacromolecules (2017) 18 : 3260-3272, doi: 10.1021/acs.biomac.7b00905.  A. Houben et al., WO 2017/005613.  L. Tytgat et al., Acta Biomaterialia (2019) accepted.  T. Qazi et al., ACS Biomaterials Science & Engineering (2019) submitted.  J. Van Hoorick et al., Advanced Healthcare Materials (2019) submitted.
8:30 AM - *SB04.09.02
Adaptable Hydrogels as Custom Bioinks
Stanford University1Show Abstract
Despite the rise of 3D printing of thermoplastics both in industry and the general public, a key limitation preventing the widespread use of cell-based 3D printing is the lack of suitable bioinks that are cell-compatible and have the required properties for printing. Current commonly used biomaterials have distinct limitations when used as a bioink including difficulty maintaining a homogeneous cell suspension, avoiding cell damage during extrusion, customizing the printed matrix properties to facilitate cell-matrix interactions, and printing within a bath to prevent cell dehydration while preserving high print resolution. We have designed a new family of tunable biomaterials specifically designed for cell-based 3D printing. These hydrogel-based bioinks are produced from blends of engineered recombinant proteins and peptide-modified, naturally occurring biopolymers such as alginate and hyaluronic acid. These materials undergo two-stages of crosslinking: (i) weak, peptide-based, self-assembly to homogeneously encapsulate cells in a shear-thinning hydrogel within the ink cartridge and (ii) stimuli-responsive crosslinking post-printing to rapidly stabilize the construct. Benefits of this two-stage crosslinking strategy include the prevention of cell sedimentation within the ink cartridge, mechanical shielding of the cell membrane from damaging extrusion forces during printing, rapid post-print self-assembly within an aqueous bath that prevents cell dehydration, and fine-tuning of the printed scaffold mechanical properties for optimal cell-matrix interactions.
9:00 AM - SB04.09.03
Laser Direct Writing of Multi-Metal Microstructures in Hydrogel—From Core-Shell Nanoparticle Formation to Spatially-Selective Plasmon Absorption
Manan Machida1,Takuro Niidome2,Hiroaki Onoe1,Alexander Heisterkamp1,3,4,Mitsuhiro Terakawa1
Keio University1,Kumamoto University2,Gottfried Wilhelm Leibniz University Hannover3,Laser Zentrum Hannover4Show Abstract
For development of hydrogels to novel biomedical devices such as wearable or implantable devices, it has been desired to provide hydrogels with specific optical, electrical, or mechanical properties. Since metallic micro- and nanostructures exhibit unique properties depending on the size, shape, and material of the structures, further high-functional flexible devices can be realized if the metal structures are able to be fabricated spatial selectively inside a hydrogel. We demonstrated spatially-targeted fabrication of metal microstructures in poly(ethylene glycol) diacrylate (PEGDA) hydrogel by using femtosecond laser, in which multi-photon photoreduction of metal ions occurs in the tightly focused space of the laser pulses. The metal microstructures were fabricated along a predefined trajectory by using computer-aided laser scanning. We fabricated gold, silver, and gold/silver bimetallic structures coexisting in the same hydrogel in a stepwise manner by taking advantage of the hydrogel’s ionic permeability. Red and yellow colors were observed for the fabricated gold and silver microstructures, respectively, which are attributed to the plasmonic resonances of the respective metal nanoparticles. Moreover, the absorbance peak of the fabricated bimetallic structures shifted from those of the single metal structures. EDX analysis revealed that the fabricated bimetallic structures consist of core-shell nanoparticles. Our technique allows to create arbitrary three-dimensional (3D) dissimilar metal microstructures, which provides the site-selective optical properties within the same supporting hydrogel that can be applied for various applications including optically-driven actuators and sensing applications.
9:15 AM - SB04.09.04
Visualizing Morphogenesis through Instability Formation in 4D Printing
Mutian Hua1,Dong Wu1,Jiaqi Song1
University of California, Los Angeles1Show Abstract
Heterogeneous growth in a myriad of biological systems can lead to the formation of distinct morphologies during the species’ maturation processes. We demonstrate that the distinct longitudinal buckling observed in pumpkins can be reproduced using 4D printing of stimuli responsive materials, taking advantage of digital light processing (DLP) 3D printing and stimulus-responsive materials. The mechanical mismatch between the different printed regions results in buckling instability on the surface. The initiation and formation of buckles are governed by the ratio of core/shell radius and the difference in swelling ratio and stiffness of the core and shell. For a thin shell, the buckles are more likely to occur, which is corresponding to the phenomenon that buckling initiates at the top few layers. The number of buckling increases from 4 to 44 as the swelling ratio of the shell decreases. Furthermore, the rigid core not only acts as a source of confinement laterally, but it also sets a boundary at its ends, exerting compressive stress and inducing buckling formation along the shell layer. This heterogeneous structure with controllable buckling geometrically and structurally behaves much like the plant’s fruits.
9:30 AM - SB04.09.05
3D Bioprinting Vascularized Hydrogel Constructs for Cancer Models
Chya-Yan Liaw1,Murat Guvendiren1
New Jersey Institute of Technology1Show Abstract
3D bioprinting is an emerging manufacturing approach to fabricate (cell-laden) hydrogel constructs with embedded microchannels, which are potentially useful for fundamental studies to understand vascularization and angiogenesis, and for developing organ-on-a-chip devices for disease modeling. In this work, we developed a novel bioprinting approach to print a sacrificial ink within photocurable matrix hydrogels. Micro-channels are formed when sacrificial hydrogel is dissolved post-printing. Our approach differes from commonly utilized extrusion-based free-from printing approaches, as it doesn't require a support bath or a shear thinning behavior for the matrix hydrogel to enable needle motion. To achieve this, a photocurable hydrogel is printed layer-by-layer as usual, but each layer is exposed to light briefly (seconds) to create partially crosslinked, self-supporting layer. At a desired thickness, immediately after the layer is printed, prior to partial crosslinking step, sacrificial hydrogel is directly printed within this viscous uncrosslinked layer. The layer is then exposed to light to confine and support the sacrificial hydrogel. After fully crosslinking the system, sacrificial hydrogel is washed away, forming a channel. This approach allows bioprinting of cells with the matrix material and seeding of cells into channels after the sacrificial ink is removed. To further utilize our approach, we developed a photocurable bioink formulation enabling cell-mediated degradation, allowing cells to remodel their surrounding microenvironment. We fabricated a perfusable hydrogel device using these bioinks to investigate the behavior of cancer cells within vascularized 3D hydrogel microenvironment.
9:45 AM - SB04.09.06
3D Printed Hydrogel-Based Electrical Impedance Tomography Sensor for In Situ Monitoring of Deformation
Zhijie Zhu1,Hyun Soo Park1,Michael McAlpine1
University of Minnesota Twin Cities1Show Abstract
The ability to directly print soft, compliant biomedical devices and sensors on the skin and inside the body could enable revolutionary advances in portable healing, wound monitoring, and traumatic shock reduction. Previously, we have shown the ability to directly 3D print functional materials on moving freeform surfaces, in which the rigid-body motion of the target surface can be tracked via a closed-loop feedback control system. Specifically, we were able to directly 3D print a functional electronic circuit directly on a moving hand, using the printer nozzle to “tattoo” electronics. Here, the capability of this adaptive 3D printing system is expanded for the first time to track the deformation of target surfaces, such as expansion and contraction of soft tissues. We demonstrate that the motions and time-variant geometries of the target surface can be estimated on-the-fly and in a closed loop fashion via machine learning from a data set of 3D scans and a real-time visual tracking system. Using this approach, a unique and conformal ionic hydrogel sensor was directly printed on a ‘breathing’ swine lung in vitro under respiration-induced deformation. The ionic hydrogel sensor is compliant to the soft tissue surface and can monitor the tissue deformation utilizing electrical impedance tomography, which provides a spatial mapping of the deformation. This adaptive 3D printing method for the direct fabrication of soft, stretchable sensors on deforming surfaces may enhance robot-assisted medical treatments and minimally-invasive procedures with additive manufacturing capabilities, enabling autonomous, direct printing of wearable electronics and biological materials on and inside the human body.
10:30 AM - SB04.09.07
Ultrashort Self-Assembling Peptides for Robotic 3D Cell Bioprinting under Physiological Conditions
Hepi Hari Susapto1,Kowther Kahin1,Zainab Khan1,Salwa Alshehri1,Sherin Abdelrahman1,Jordy Homing Lam1,Xin Gao1,Charlotte Hauser1
King Abdullah University of Science and Technology1Show Abstract
3D bioprinters have received considerable attention in latest studies, primarily owing to their customization and flexibility that provide an advantage over traditional lab-grown organ development. By printing with a bioink, productivity and efficacy are enhanced while accelerating medical procedures like organ transplantation. Many different natural bioinks have also been studied for their potential application in 3D bioprinting, such as matrigel, collagen, and alginate, all of which are obtained from non-human sources. Because of their complex and variable composition, these natural bioinks are not suitable for controlled modifications. Complications in controlling these materials’ physiological variables (e.g. pH and salt concentration) also pose challenges in mimicking the extracellular matrix (ECM). Their batch-to-batch fluctuations can also have a significant impact on the sustainability and immunogenicity of the bioprinted 3D structures, which are among the drawbacks of using these bioinks for tissue/organ growth or downstream clinical applications. In addition, 3D molds based on polymers are a prerequisite for the manufacturing of 3D structures using natural bioinks. This introduces more difficulties for complex molds as they are not easily constructed. The issues associated with natural bioinks can be solved by harnessing a synthetic peptide material that can self-assemble to form 3D nanofibrous scaffolds, in addition to other benefits, such as control over composition and ease of chemical modifications. In this study, we have developed an in situ bioprinting technique that enables the printing of cells under true physiological conditions using ultrashort self-assembling peptides as bioinks. Previously, we designed a set of ultrashort peptide bioinks that demonstrated adequate mechanical strength, rigidity, and shape fidelity on glass substrates. To understand more about the self-assembly process of these peptides, the morphology, secondary structure and viscoelastic property of self-assembled peptide nanostructures were furthered characterized, in addition to molecular dynamics simulations of these peptides in water to study fiber formation at the atomic scale. The 3D structure of these assembled peptides were then determined using NMR spectroscopy to support the simulation result. An extruder was engineered to be compatible with the peptide-based hydrogel and installed for improved printing by a 3D bioprinting robotic arm. We believe that as we print under truly physiological conditions, our unique in situ 3D bioprinting technique offers benefits over current bioprinting methods. The bioprinting methods that makes use of UV-treatment, chemical crosslinking, and viscous bioinks that result in stress to the cells can also be avoided with our method. Furthermore, the self-assembled peptide bioinks prove to be durable, readily printable, and offer great biocompatibility with tested cell lines including human dermal fibroblast cells and human mesenchymal stem cells. From the results, the cell proliferation in printed peptide hydrogels after 14 days and 21 days of culture was higher than that of alginate gelatin. RNA sequencing was also conducted to compare the difference in gene expression patterns in HDFn cells cultured in 2D, 3D bioprinted in IVZK and alginate-gelatin (AG) bioinks. We further demonstrate that various nanomaterials can easily be synthesized or incorporated into the 3D bioprinted peptide scaffolds that create a new opportunity for functionalized 3D scaffolds for a wide range of applications, including tissue engineering and regenerative medicine.
10:45 AM - SB04.09.08
Biodegradable Thermoplastic Elastomers as 3D-Printed Nerve Guidance Channels for Peripheral Nerve Repair
Yang Hu1,Robert Newman1,Adam Ekenseair1,2,3
Northeastern University1,The University of Texas at Austin2,University of Arkansas–Fayetteville3Show Abstract
The peripheral nervous system (PNS) is a complicated and extensive network of nerves that are the means by which the brain and spinal cord control the rest of the body. The PNS is fragile and can be easily damaged by injuries or trauma. Surgical treatment is the only remedy currently available, with the gold standard for defects greater than 8 mm being autologous nerve grafts; however, only around 40% of the 1.8 million US PNS patients each year regain normal function. In addition, nerve grafts have been particularly ineffective at repairing critical-size nerve defects (> 3 cm). Scaffold-based strategies where a tubular nerve guidance channel (NGC) is used to bridge the nerve defect have been promoted as a potential alternative that could avoid the additional surgeries and associated donor site morbidity involved in the harvest of nerve grafts. Clinicians have thus increased the use of NGCs combined with current surgical therapeutics. However, current NGCs lack patient-specific tunability and are only approved for small-gap (< 3cm) injuries by the U.S. Food and Drug Administration (FDA). Current research efforts are focused on creating more complex NGCs that can support the regeneration of critical-size defects.
In this context, our research seeks to use additive manufacturing technologies to create bioactive and cellular NGCs on demand for the repair of critical-size nerve defects. Recently, 3D printing has been increasingly used in research and medical therapeutics for rational, computer-aided design of biomaterial-based scaffolds with complex architecture. Furthermore, printing with co-axial extruders can enable the direct printing of layered tubular structures for use as NGCs. The NGCs should contain an outer flexible shell that seeks to mimic the mechanical properties of the surrounding biological tissue and enable diffusion of nutrients to support encapsulated cells. The use of biodegradable block copolymers with both hydrophilic and relative hydrophobic functions can provide a flexible, partially-hydrated, biocompatible and bioresorbable NGC shell.
In this study, A-B-A type triblock copolymers of PLLA-PEG-PLLA were synthesized using varied ratios of PEG and PLLA. The resulting block copolymers were characterized with gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR) to determine molecular weight, polymer structure, and thermal behavior. In addition, equilibrium water content, degradation rates, mechanical properties, and cell response were all evaluated and correlated to the polymer structure.
11:15 AM - SB04.09.10
A 3D Bioprinted Brain-Like Co-Culture Network towards Modeling Neural Cell Interactions
Yasamin Aliashrafi Jodat1,2,SuRyon Shin1,3,Yi Chen Ethan Li4,Minoru Hirano1,Roya Samanipour1
Harvard Medical School1,Stevens Institute of Technology2,Brigham and Women's Hospital3,Feng Chia University4Show Abstract
Reproducing the remarkable features of the multi-cellular three-dimensional (3D) environment of the brain in vitro, such as 3D cell-cell interactions, is considered a crucial step in creating reliable drug testing platforms for a variety of brain diseases. More specifically, the intercellular interactions between neural cells is a key factor to regulate brain functions and ensure health homeostasis. Recent advances in microfabrication and biomanufacturing techniques such as 3D bioprinting has opened new doors to create microscale 3D platforms to study 3D cell-cell interactions and mimic the structural and functional behavior of tissues in vitro. Here, a 3D brain-like co-culture construct is developed using multi-material embedded 3D bioprinting technology to study the neuron-glia interactions. Specifically, free-standing neuron-laden 3D structures are fabricated in a self-healing glia-laden support bath, resembling a brain-like tissue with neural fibers and glia-neuron interactions. The biomaterials were engineered to provide tunable soft tissue stiffness while allowing the creation of 3D geometries and complex networks. Moreover, the biomaterials showed excellent support for neural stem cell differentiation and glial cell spreading. Additionally, the differentiated neurons in the printed fibers exhibited glutamate synthesis capabilities, proving that the engineered brain-like tissue constructs can recapitulate neurotransmitter interactions, namely the glutamate-glutamine cycle. Eventually, the engineered brain-like co-culture constructs can prove useful for studying the levels of glutamate in the diseased brain and provide a reliable and highly reproducible in vitro platform for neurological drug screening and brain disease modeling.
SB04.10: Fundamentals and Applications II
Thursday PM, December 05, 2019
Hynes, Level 3, Room 302
1:30 PM - *SB04.10.01
Breaking the ‘Lock-and -Key’ Rule—Engineering Multi-Responsiveness in Intrinsically Disorder Proteins and Hydrogels
Naba Dutta1,2,Rajkamal Balu1,Namita Choudhury1,2,Anita Hill3
RMIT University1,The University of Adelaide2,CSIRO3Show Abstract
Nature, through evolution has perfected elegant arrays of proteins with unusual characteristics and amazing functionalities using limited number of amino acid residues under mild conditions. This understanding has instigated a significant paradigm shift towards the design and synthesis of functional materials using biomimetic proteins and peptides incorporating nature's exquisite molecular design. Traditionally, it is being considered that a unique biological function of a protein is defined by its specific highly structured state. Contrary to this view, recently, the natural abundance and functional importance of intrinsically disordered proteins (IDPs) has been recognized.1-3 The goal of this presentation is to highlight our body of recent work on genetically engineered resilin-mimetic protein-polymers (RMPs) and gels; and their disordered-based functionality. We will discuss their unusual molecular architecture, dynamics of their structural ensembles, advanced multi-stimuli responsiveness, structure-directed biomineralization process, their responsive hydrogels; and attempt to elucidate the molecular origin of their unusual adaptability.
Native resilin is a member of the family of elastic proteins that includes elastin, gluten, gliadin, and spider silks and is purported to be the most resilient elastic material known with resilience >97%. The structural composition of rec1-resilin is dominated by 18 copies of a 15-residue consensus sequence: -[Gly-Gly-Arg-Pro-Ser-Asp-Ser-Tyr-Gly-Ala-Pro-Gly-Gly-Gly-Asn]- .We have employed a combination of both modelling tools and state-of-the-art spectroscopic, microscopic and scattering techniques including FTIR, UV-Vis, AFM, TEM, DLS, SAXS, SANS, USANS to develop deeper understanding and elucidate the structural organization and function. Our work has revealed that RMPs (synthesized using recombinant DNA technology) are IDP 4,5 that show very high flexibility and demonstrates multi-stimuli responsiveness (responsive to pH, ion content, temperature) including unusual dual phase behaviour (display both UCST-upper critical solution temperature and LCST-lower critical solution temperature).6,7 Furthermore, we have demonstrated our ability to tune the thermo-responsiveness of RMPs 6-8 and employed the unusual multi-stimuli responsiveness of RMPs to create patterned surfaces,9 responsive interfaces10 and tunable co-assembled hydrogels.11 We have developed a directed self-assembly approach for colloidal synthesis of RMP-mediated size-controlled metallic nano-partilces, nano- clusters12,13and colloidal catalyst ink based electrocatalyst layer14 in aqueous medium under mild condition. Overall, the research has revealed the potential of the IDPs to pave the way for the design of novel biomaterials and nano-bio conjugates.
1. V. N. Uversky, Frontier in Physics, 2019, 7, article10.
2. J Whittaker, R Balu, N.R Choudhury, N. K. Dutta, Polym. Int. 2014, 63,1545.
3. R Balu, J. Whittaker, N. K. Dutta, C.M Elvin, N.R. Choudhury, J. Mater. Chem. B, 2014, 2, 5936
4. R. Balu, N. Choudhury, N. K. Dutta, et al. Sci. Reports 2015, 5, doi:10.1038/srep10896.
5.R. Balu, J. P. Mata, R. Knott, N. K. Duttaet al. J. Phys. Chem. B 2016. 6490.
6. N. K. Dutta, M.Y. Truong, N. Choudhury, et al. Angew. Chem. Int. Ed. 2011, 50, 4428.
7. R Balu, N. K. Dutta, NR Choudhury, et al. Acta Biomaterialia 2014,10, 4768
8. M. Y. Truong, N. Dutta, N. Roy Choudhury, et al. Biomaterials 2010, 31, 4434.
9. M. Y. Truong, N. K. Dutta, et al., Biomaterials 2011, 32, 2786.
10. N. K. Dutta, N. Choudhury, M. Y. Truong, et al. Biomaterials 2009, 30, 4868.
11. J. L Whittaker, N. K Dutta, N. Roy Choudhury et al. Langmuir 2015, 2015, 8882.
12. S. Mayavan, N. Dutta, N. R. Choudhury, et al. Biomaterials 2011, 32, 2786.
13. R. Balu, L. Bourgeois, N. K. Dutta, et al. J. Mater. Chem. B, 2015, 3, 6580.
14.R. Balu, N. Choudhury, J. P Mata, L. de Campo, C. Rehm, A. J Hill, N. K. Dutta, ACS Appl. Materi. Interfaces, CS Appl. Mater. Interfaces, 2019, 11, 9934.
3:00 PM - *SB04.10.03
Programmed Deformations of Composite Hydrogels into Multi-Stable Configurations
Ziliang Wu1,Chen Yu Li1,Zhi Jian Wang1
Zhejiang University1Show Abstract
It is well-known that nature utilizes controlled deformation strategies to produce complex three-dimensional (3D) shapes of plant organs. Inspired by the natural activated systems, the realization of 3D shapes of artificial materials by programmed deformations has recently attracted great interest as a delightful concept and a practical technology with promising applications in biomedical devices, soft robotics, and flexible electronics. One fundamental task is to exploit new deformation modes and reveal the deformation mechanism. Shape transformations of intelligent materials are realized by switching the environmental conditions. However, it's challenging to form multi-stable morphing structures under the same condition. We present here a photolithographic method to pattern one responsive polymer in a non-responsive hydrogel sheet with well-designed gradient structures. Under external stimuli, the swelling mismatch results in the built-up of internal stress and thus programmed deformations of the composite hydrogel. Owing to the bi-stable nature of buckling deformation, i.e. the hydrogel sheet with in-plane gradient buckles upward or downward with almost equal possibility, the integrated composite hydrogel with multiple units of in-plane gradient structure has multiple distinct configurations. We will report both experimental and simulation results to demonstrate that various stable configurations can be obtained in one composite hydrogel under the same condition by controlling the buckling direction of each unit by a selective pre-swelling step. This concept and strategy should be applicable for other intelligent materials and merit their applications in diverse areas.
3:30 PM - SB04.10.04
Expanding Gelation Conditions in Metal-Coordinated Hydrogels
Seth Cazzell1,Niels Holten-Andersen1
Massachusetts Institute of Technology1Show Abstract
Polymer networks with dynamic physical crosslinks have generate widespread interest as tunable and responsive viscoelastic materials. A subclass of these materials containing multi-component, or complimentary, crosslinks, such as host-guest interactions and metal-coordination, are limited by their ability to percolate under stoichiometric imbalances of their crosslink components. Here we present a method to relax this stoichiometric requirement through the use of a third component, a dynamic, free competitor. This approach to expand the conditions that result in gelation is demonstrated experimentally with metal-coordinated hydrogels, and simulations are used to show the thermodynamic criteria that are necessary to expand the previously understood tight stoichiometric tolerance for gelation. This work can then be generally applied to advance engineering of the broadening class of polymer materials with dynamic crosslinks.
3:45 PM - SB04.10.05
Molecular Understanding of Bond Dissociation Kinetics in Metal-Coordination Transient Hydrogels Using Simulation and Experiment
Eesha Khare1,Markus Buehler1,Niels Holten-Andersen1
Massachusetts Institute of Technology1Show Abstract
Metal-coordination hydrogels represent a new class of advanced materials for biomedical, composites, and structural applications. The dynamic properties enabled by this bonding are useful for the development of hydrogels in drug delivery, tissue scaffolds, and wound-healing, where tunable viscoelastic properties are critical in determining biological response. Metal-coordination bonds are reversible and tunable, unlike more static ionic or covalent chemical crosslinks commonly employed in hydrogels that permanently break upon fracture. As they have the capacity to break and reform after rupture, metal-coordination bonds can act as sacrificial bonds that help increase the fracture toughness of a material. Such sacrificial bonds are also important molecular motifs in biological systems where metal-mediated bonds play significant roles in protein folding and unfolding, rupture, and shock absorbance in many biological tissues such as mussel threads and other marine organisms. In fact, incorporating sacrificial metal bonding in hydrogels enables us to achieve transient mechanical properties which can be dynamically tuned over several time scales. Despite the emergence of new, dynamic properties enabled by metal-coordination chemistry, a fundamental understanding of the relationship between the chemistry, effective bond properties, and overarching macroscale mechanical properties of such systems is yet to be developed.
The development of histidine-divalent metal-coordination hydrogels presents a good model system with which to study the role of metal coordination in the mechanics of hydrogels (Grindy et al., 2015). In this system, 4-arm polyethylene glycol (PEG) is end-functionalized with histidine derivatives that can coordinate with divalent metal cations (Zn2+, Ni2+, Cu2+) to form transient crosslinked gels. The kinetics of metal-coordination bonding to produce dynamic viscoelastic properties can be tuned through simple levers such as pH, temperature, and chemistry. This study couples multiscale computational modeling with experiment to characterize the molecular bonding landscape and kinetics of histidine functionalized PEG hydrogels. Density functional theory (DFT) and molecular dynamics (MD) are used to characterize the equilibrium bonding configuration and optical properties of the metal cations with the histidine ligand. The energy landscape of this bond is probed through metadynamics calculations and MD. Simulation results are compared with rheological and spectroscopic experimental characterizations of the hydrogels. Based on insights gained into the role of ligand-metal binding, coordination of surrounding ligands, and polymer physics from these calculations and experiments, this work proposes key design criteria for how this new class of metal-coordination chemistry hydrogels can be advanced for biological and environmental applications with dynamic, self-healing properties.
4:00 PM - SB04.10.06
Bottom-Up Assembled Hierarchical Bacterial Network of Chronical Stability
Andrew Xu1,Pu Deng1,Xiaocheng Jiang1
Tufts University1Show Abstract
Bioprinting is a method to create ex-vivo replicates of biosystems through precise three-dimensional (3-D) assembly of basic biocomponents into hierarchical structures with rationally designed functionalities. In the context of energy and environmental science, bacteria are widely exploited as self-sustainable biocatalysts to build systems that are capable of processing complex biochemical reactions and bioenergy transduction with superb efficiency and specificity at low-cost, mild reaction conditions. Ion crosslinked alginate is a popular supporting material for bacteria printing due to its fast and reliable gelation, structural similarities to the polysaccharide in native biofilms, and sufficient porosity for effective nutrients/metabolites transport. The lifetime of alginate supported bioprints, however, is quite limited, as a result from weak and reversible ion-alginate bonds, which initiate the leakage of encapsulated bacteria and eventually leads to the complete failure of the printed structures. To ultimately overcome this challenge, in this work, we modulated the alginate structure to strengthen the intermolecular interactions and improve the structural integrities of the bio-printed bacteria networks. Additionally, reduced graphene oxide (rGO) was introduced into this bacteria-alginate matrix, which further enhances the long-term stabilities through strong rGO-alginate interactions. These approaches result in the significant increase in the lifetime of bio-printed bacteria networks as the concentrations of the escaped/floating bacteria were reduced by 400% after 24 hours of culture. Based on this platform, we designed and constructed a 3-D living filter for toxic ions remediation using S. loihica encapsulated alginate microfibers as one-dimensional building blocks. Additionally, by tuning the composition and microstructure from bottom up, the degradability, bacteria loading density, and mass transport efficiency can be customized to meet the requirements of various wastewater conditions. The current work provides important insight about the fundamentals of bio-printing design and process and could open up new opportunities toward the creation of chronically stable biosystems with predictable and versatile functions encoded.
4:15 PM - SB04.10.07
Anisotropic Hydrogels by Magnetically-Oriented Nanoclay Suspensions
SungHo Yook1,Mukerrem Cakmak1
Purdue University1Show Abstract
With the presence of nanoparticles in a 3D hydrogel network, nanocomposite polymer hydrogels can exhibit additional functional properties in mechanical strength, swelling kinetics, and transparency. The nanostructure of nanocomposite hydrogels is generally isotropic because the nanoparticles entrapped within the 3D hydrogel network are randomly dispersed. However, the anisotropic features in hydrogels are often necessary to mimic anisotropic hierarchical structures in nature organism or to develop soft materials with directional mechanical/optical/ thermal properties. In this study, anisotropic nanocomposite hydrogels were achieved by orienting nanoclay in a hydrogel network. The aqueous suspension of nontronite nanoclays, which are sensitive to magnetic fields due to high contents of ferric ions (Fe3+), were oriented in various strength of the magnetic field and then the final morphology was fixed by the synthesis of the hydrogel. The nanostructure of the anisotropic hydrogels was characterized by measuring birefringence, 2D Small Angle X-ray Scattering (SAXS), and transmission. The magnetic field-induced birefringence of anisotropic hydrogels increased with the applied magnetic field strength in a range between 0 to 9 Telsa in all different concentrations (0.05wt%, 0.1 wt%, 0.2 wt%, and 0.4 wt%) as the orientation degree of nanoclay particles increased. The birefringence was also proportionally increased with nanoclay concentrations from 0.05 wt% to 0.2 wt%, but it significantly decreased at 0.4 wt% concentration. Furthermore, 2D SAXS revealed that the long axis of nontronite platelets was oriented parallel to the applied magnetic field direction. With 2D SAXS patterns, the orientation order parameter was calculated at different magnetic field strength and concentrations. At 0.1 wt% nanoclay concentration, the orientation order parameter increased up to 0.67 as applied magnetic field strength increased. The samples prepared in 9 Tesla showed high orientation order parameter in all different concentrations. The field-induced birefringence and orientation order parameter showed a linear correlation over the magnetic field strength range from 0 Tesla to 9 Tesla. The anisotropic hydrogels also showed the 7% and 8% increase in optical transmission to applied magnetic field direction at 0.1 wt% and 0.2 wt% concentrations.
4:30 PM - SB04.10.08
Printable Ag-Based Conductive Composites
Yunsik Ohm1,Chengfeng Pan1,Michael Ford1,Xiaonan Huang1,Carmel Majidi1
Carnegie Mellon University1Show Abstract
Conductive and stretchable materials are important components in soft electronics and sensors that are used for emerging applications in soft robotics and wearable physiological monitoring. Compared with other stretchable conductors composed of different types of polymers, conductive hydrogels are promising candidates for soft electrode materials due to their mechanical compliance, which is similar to biological tissues (0.5-500 kPa) such as human skin; compatibility with aqueous environment due to high water content; and inherent ability to adhere to other materials. However, most conducting polymer-based hydrogels are ionic conductors, so they are not able to deliver direct current (DC) but instead support alternating current (AC). Here, we introduce a novel and facile method for making a soft (<1 MPa), highly stretchable (>200% strain), and electrically conductive (>103 S/cm) hydrogel composite that can be functional in water and conductive enough to transmit digital signals. The composite is composed of micron-sized silver (Ag) flakes (2-5 micrometers) distributed over an alginate-acrylamide based hydrogel matrix. The mixture of silver flakes and alginate-acrylamide hydrogel is not electrically conductive immediately after curing; however, it can achieve electrical conductance while maintaining its soft and deformable nature by controlling the amount of water inside the composite through drying. During the drying process, evaporating water enables the formation of a percolating network of silver flakes within the hydrogel matrix, which makes the conductive gel electrically conductive (maximum initial conductivity ~90000 S/cm). Moreover, the inherent mechanical properties of the hydrogel are preserved (e.g. maximum strain limit ~250% while maintaining electrical conductivity). We demonstrate the utility of the conductive hydrogel ink by powering a soft swimming eel that can swim with the help of bi-stable SMA actuators. We will also present a stencil-printed stretchable circuit in which several surface mounted LEDs are continuously powered through use of the conductive hydrogel ink. The stretchable and conductive hydrogel ink that we present here represents a new route to controlling conductivity in conductive hydrogel.
4:45 PM - SB04.10.09
Mussel Inspired Tough Double Network Hydrogel as Shapeable Adhesive
Xiaohan Wang1,Yisheng Xu1,Xuhong Guo1
East China University of Science and Technology1Show Abstract
Hydrogels with excellent adhesive and mechanical properties have attracted extensive attractions due to its application prospects in various fields such as wound dressing, electronic skin and wearable devices. However, few has successfully prepared “tough and sticky” hydrogel with desirable and tunable performance. In this work, dopa modified hyaluronic acid (HA-dopa) was firstly introduced to the double network (DN) system, which greatly improved the mechanical and adhesive performance of the original HA-Acrylamide (AAm) DN hydrogel. By modulating external parameters such as pH and Fe3+ concentration of the precursor solution, the overall property of the hydrogel could be well-tuned. Moreover, a non-monotonic dependence of the HA-dopa content on mechanical and adhesive enhancement could be clearly observed. Based on this phenomenon, we proposed a new mechanism that the catechol moiety within HA-dopa played a different role and served as chemical crosslinker to reinforce the hydrogel, leading to a more compact network and improved overall performance. Therefore, as an effective approach to enhance the adhesive and mechanical property of hydrogel, this mussel-inspired practice would provide valuable insight into designing functional hydrogel and elastomer for various applications.
Marc In het Panhuis, University of Wollongong
Namita Choudhury, RMIT University
Ferenc Horkay, National Institutes of Health
Jurgen Groll, University of Wurzburg
SB04.11: Fundamentals and Applications III
Friday AM, December 06, 2019
Hynes, Level 3, Room 302
8:30 AM - SB04.11.01
Biomimetic Cartilage Model Exhibiting Matrix “Prestress”
National Institutes of Health1Show Abstract
A critical feature of extracellular matrix (ECM), in general, and cartilage tissue, in particular, is the prestress that develops within the tissue matrix. Cartilage is a composite medium whose proteoglycan (PG) components imbibe water, while its confining collagen matrix resists PG swelling. This balance of forces results in a significant matrix prestress—on the order of four atmospheres—under no external load. Our group recently developed a composite polymeric medium consisting of poly-acrylic acid (PAA) microgel assemblies (mimicking the PG phase) dispersed within a PVA gel network (mimicking the collagen matrix). This hydrogel composite exhibits remarkable load bearing ability, and key quantitative and qualitative material behaviors observed in human cartilage specimen. The osmotic modulus of this aggregate gel system provides an eloquent measure of its load bearing ability.
9:00 AM - SB04.11.02
Transport into Stiff Gel-Like Deformable Articular Cartilage for Drug Delivery
Massachusetts Institute of Technology1Show Abstract
Traumatic joint injury in individuals at any age can initiate cartilage and subchondral bone degeneration in the presence of elevated levels of inflammatory cytokines, leading to post-traumatic osteoarthritis (PTOA). There are currently no disease modifying drugs for osteoarthritis or PTOA, and a major challenge is the ability to achieve sustained levels of potential therapeutics inside a target tissue such as cartilage, with no side effects, after intra-articular delivery. We use in vitro organ culture models to study the beneficial effects of combination therapeutics (e.g., glucocorticoids, growth factors) to inhibit matrix degradation and cell apoptosis in cartilage. These experiments are performed with isolated cartilage explants, intact osteochondral plugs or osteochondral plugs in the presence of synovium explants (the latter known to release inflammatory proteins). To simulate a traumatic joint injury, the cartilage is also subjected to an initial acute impact compressive load. Parallel in vitro and animal studies are aimed at approaches to targeted tissue drug delivery. In particular, charge based intra-cartilage delivery of glucocorticoids and/or growth factors has been enabled using cationic nanoparticles including Avidin and supercharged green fluorescent proteins. In studies of cartilage degradation and repair, it is important to assess the mechanical function of newly synthesized tissue and constituent matrix molecules at the molecular scale. We have therefore developed and used an AFM-based wide-bandwidth rheology system to measure the dynamic nanomechanical behavior of normal and degraded cartilage as well as end-grafted aggrecan brush layers over the frequency ranges relevant to impact injuries. The effects of mechanical loading on cartilage degradation and repair is also under study, as it is very important to clinical rehabilitation.
9:30 AM - SB04.11.03
Direct Visualization of Functional Crosslinkers in Swollen PNiPAm Based Microgels
Gopal Kenath1,Apostolos Karanastasis1,Yongdeng Zhang2,Mark Lessard2,Joerg Bewersdorf2,Chaitanya Ullal1
Rensselaer Polytechnic Institute1,Yale2Show Abstract
The spatial distribution of cross-links in bulk gels and colloidal gel particles impacts their mechanical and transport properties. Here we report on the spatial distribution of dye tagged crosslinkers of colloidal PNIPAM microgels revealed by super-resolution microscopy at the level of individual particles as well as at the ensemble level. Using a W-4PiSMSN microscope we demonstrate the presence of higher crosslink nanodomains within the already dense cores of the microgels. Additionally, we show that the average probability density profile, extracted from super resolution, can be used to extract quantitative relative reaction rate constants. We prove this by coupling the localization probability density profile with the temporal volumetric evolution of the particles to accurately predict the consumption of the dye tagged species with time. These predicted consumption curves are fit to accepted kinetic models for precipitation polymerization of microgels to extract relative rate constants for the functional cross-linker to n-isopropylacrylamide and N,N’-methylene-bis-acrylamide.
9:45 AM - SB04.11.04
A Review on the High Potential of High-Energy Electron Crosslinking of Hydrogels towards Precisely Tailored Biomimetic Materials
Stefanie Riedel1,2,Philine Hietschold2,1,Stefan Mayr1,2
Leibniz Institute for Surface Modification1,Universität Leipzig2Show Abstract
Tailoring hydrogels and their properties for customized applications is a highly interesting task in tissue engineering to develop biomimetic materials for biomedical applications. Thereby, crosslinking processes are commonly used since the degree of crosslinking precisely determines the material properties. Among the diverse techniques of crosslinking, high-energy electron treatment is a highly advantageous method, which allows reagent-free tuning of structural and mechanical features of hydrogels while chemical structure and cytocompatibility are excellently maintained.
Within this contribution, we will introduce electron beam treatment and we will show the high potential to tailor precisely biological hydrogel properties. In particular, we will show how electron beam treatment effectively tunes network structure and viscoelastic properties of biological hydrogels such as collagen. In addition, we will demonstrate their excellently maintained chemical structure and cytocompatibility. With this, our research describes a promising reagent-free method to tailor precisely hydrogel properties for prospective biomedical applications.
 S. Riedel, P. Hietschold, K. Krömmelbein, T. Kunschmann, R. Konieczny, W. Knolle, C. Mierke, M. Zink and S. G. Mayr, Materials & Design 168, 107606 (2019)
10:30 AM - SB04.11.05
Electrical “Suturing” of Polyelectrolyte Hydrogels to Reseal Cut or Damaged Tissues
University of Maryland1Show Abstract
This talk will present studies from our lab on the electrically induced adhesion of hydrogels and beads made from polyelectrolytes. When a rectangular strip of a cationic gel (connected to an anode) is contacted for just a few seconds with a strip of anionic gel (connected to a cathode) under a voltage of ~ 10 V, the two gel strips form a strong adhesive bond. When the polarity of the electrodes is reversed, the phenomenon is reversed, i.e., the gels can be easily detached.
While the above phenomenon of ‘electro-adhesion’ has been reported before for hydrogels, we show that it is much more general and widespread. Specifically, we can substitute either of the above gels with a spherical bead made using charged biopolymers such as chitosan or alginate. The same electro-adhesion works to join beads to gels, or two beads to each other. In turn, electro-adhesion can be applied for the pick-up and drop-off of soft cargo, and for the sorting of beads. Most interestingly, the same phenomenon also works with certain animal tissues. That is, many tissues are anionic, and we show that cationic gels can be electro-adhered to them. We thereby demonstrate that cuts or tears in tissues can be electro-sealed using beads or gel strips. As an extreme case, two severed pieces of a tube can be stuck back together using a gel strip that spans both cut segments; this is thereby an example of a needleless suture using only hydrogels and an electric field.
11:00 AM - SB04.11.06
Gelation Control in Polysaccharides
Juan Londono1,Kyle Kim2,Natnael Behabtu2,Laura Clinger1
DuPont1,DuPont Biomaterials2Show Abstract
Polysaccharides are derived from renewable resources, supporting trends to reduce the consumption of plastics made from petrochemicals. Polysaccharides consist of sugar units linked by glycosidic bonds. Seemingly small variations in the glycosidic bond often result in dramatic changes in properties [e.g. hydrophobic cellulose β-(1→4) vs hydrophilic starch α-(1→4)]. There is, in addition, the possibility of mixed linkages and complex architectures, from linear to highly branched. Finally, polysaccharides may be derivatized, with the potential of changing properties entirely. Polysaccharides therefore provide a wide platform from which polymers with diverse properties can be obtained. Due to their versatility, these polymers are ubiquitous in nature and industry.
Industrial polysaccharides are widely used as viscosity modifiers, food texturants and in oil recovery applications. The major source of industrial polysaccharides is the natural world. For example, carrageenans are a family of sulphated polysaccharides that are widely used as gelling agents and stabilizers in dairy, beverages, confectionery and meat applications. Carrageenans show a thermo-reversible disorder-to-order transition that is key for its gelling and stabilization. Although carrageenans have a long history of use, it remains unclear which physical states different carrageenans have and which intrinsic and extrinsic factors influence their physical state.
Polysaccharide viscosity depends on a structural hierarchy spanning a multitude of length scales, and a suite of analytical techniques are needed to understand the secondary, tertiary and quaternary structure of these materials. Characterization of this hierarchy from x-ray scattering, rheology, microscopy and size-exclusion chromatography are presented for carrageenan. Furthermore, polysaccharides harvested from the natural world entail issues of variability, heterogeneity, purity, and reliability. There is therefore the need for structural control at the molecular, nano and mesoscales, to improve industrial use of these polymers.
Another polysaccharide, α-(1→3)-D-Glucan (glucan), is mainly found in the cell wall of micro-organisms. A linear form of glucan can be obtained from fungi and yeasts while some bacteria produce branched glucan chains in human saliva where a connection to dental caries has been suggested. Several patents  and recent literature  have shown that the glucan polymer can be synthesized enzymatically with good yield. There are strong parallels between the glucan colloidal material as obtained from enzymatic polymerization and the hierarchical structures found in other conventional materials like fumed silica and carbon black.
Indeed, both glucan and carrageenan hold promise for viscosity modification applications such as 3D printing with the added benefit that natural polysaccharides are both renewable and biodegradable. In addition, glucan is consistent in purity and quality since it is enzymatically derived.
J O’Brien, DuPont, USP 7,000,000, January 19, 2000; and similar patents dating since 2000.
S Puanglek et al.; Scientific Reports, 6:30479, DOI: 10.1038/srep30479, 29 July 2016.
11:30 AM - SB04.11.07
A Simple Way to Synthesize a Protective ‘Skin’ around a Hydrogel
Sai Nikhil Subraveti1,Srinivasa Raghavan1
University of Maryland, College Park1Show Abstract
In nature, various structures such as fruits and vegetables have a water-rich core that is covered by a hydrophobic layer, i.e., the skin. The skin creates a barrier for chemicals from the external environment to enter the core; at the same time, the skin also ensures that the water in the core is preserved and not lost by evaporation. Currently, for many applications involving hydrogels, especially in areas such as soft-robotics or bio-electronic interfaces, it would be advantageous if a hydrogel could be encased in a skin-like material. However, forming such a skin is challenging because it would need to be a hydrophobic material with a distinct chemistry from the hydrophilic gel core. Here, we present a simple solution to this problem, which allows any hydrogel of arbitrary composition and geometry to be encased in a hydrophobic ‘skin’. Our synthesis technique involves an inside-out polymerization, where one component of the polymerization (such as an initiator) is present only in the hydrogel core while other components (such as monomers) are present only in the external medium. Accordingly, a skin, i.e., a thin polymeric layer, grows outward from the core, and the entire process can be completed in a few minutes. We show that the presence of the skin prevents the hydrogel from swelling in water and also from drying in air. Likewise, hydrophilic solutes in the hydrogel core are prevented by the skin from leaking out into the external solution. The properties of the skin are all tunable, including its thickness, its mechanical properties, and its permeability. The ability to grow such a skin readily around any given hydrogel is likely to prove useful in numerous applications.
11:45 AM - SB04.11.08
Tearing a Hydrogel of Complex Rheology
Ruobing Bai1,Baohong Chen2,Jiawei Yang2,Zhigang Suo2
California Institute of Technology1,Harvard University2Show Abstract
Tough hydrogels of many chemical compositions are being discovered, and are opening new applications in medicine and engineering. To aid this rapid and worldwide development, it is urgent to study these hydrogels at the interface between mechanics and chemistry. A tough hydrogel often deforms inelastically over a large volume of the sample used in a fracture experiment. The rheology of the hydrogel depends on chemistry, and is usually complex, which complicates the crack behavior. In this talk, we study a hydrogel that has two interpenetrating networks: a polyacrylamide network of covalent crosslinks, and an alginate network of ionic (calcium) crosslinks. When the hydrogel is stretched, the polyacrylamide network remains intact, but the alginate network partially unzips. We tear a thin layer of the hydrogel at speed v and measure the energy release rate G. The v-G curve depends on the thickness of the hydrogel for thin hydrogels, and is independent of the thickness of the hydrogel for thick hydrogels. The energy release rate approaches a threshold, below which the tear speed vanishes. The threshold depends on the concentration of calcium. The threshold may also depend on the thickness when the thickness is comparable to the size of inelastic zone. The threshold determined by slow tear differs from the threshold determined by cyclic fatigue. We discuss these experimental findings in terms of the mechanics of tear and the chemistry of the hydrogel.
SB04.12: 3D and 4D Printing II
Marc In het Panhuis
Friday PM, December 06, 2019
Hynes, Level 3, Room 302
1:30 PM - SB04.12.01
Spatially Patterned Magnetic Hydrogels for Responsive Cell Culture Applications
Dermot Brougham1,Patricia Monks2,1,Jacek Wychowaniec1,Shane Clerkin3,John Crean3,Kevin McCarthy3,Andreas Heise2,Brian Rodriguez3
School of Chemistry, University College Dublin1,Royal College of Surgeons in Ireland2,University College Dublin3Show Abstract
Responsive functional soft nanocomposite materials remain a significant focus of scientific effort worldwide due in part to their applications in biomedicine ranging from cancer treatment to biomolecule/drug delivery1 through to cell supports. Their responses to electric and/or magnetic fields, temperature, salts, pH, and light can be engineered through precise physicochemical modifications across multiple length scales and also by spatial patterning using 3D printing technologies2. Magnetic nanoparticles (MNPs) and also their clusters are used in the biomedical field in a wide range of applications from cancer treatment to MRI imaging3. The combination of MNPs and established 3D printable polymeric hydrogel formulations can provide multifunctional and stimuli-sensitive nanocomposite delivery systems with spatial-, temporal- and dosage-controlled release properties. We are interested in exploring these possibilities for tissue engineering applications.
A multi-head 3D printer was successfully built and modified to allow extrusion of Pluronic F127 hydrogels and composite gels including F127 and PEG-diacrylate with parameters of moderate temperature and pressure that would support cell viability. Magnetic nanoparticles were synthesised, stabilized and incorporated homogenously; oscillatory rheology measurements confirmed the viscoelastic properties with storage modulus values in the ~20 kPa range providing ideal materials for 3D printing well-defined architectures with high fidelity for both magnetic and non-magnetic streams. The hybrid inks showed complete shear- and temperature- recoverability/reversibility to their initial state, confirming that at particle concentrations that enable magnetic responses the necessary printability is not lost Various complex structures were printed with high resolution (~100 micron) with independent magnetic and non-magnetic patterned components and these were shown to be reproducible and robust and they could be cured in situ at magnetically responsive particle concentrations to retain the fidelity of printed features. Biocompatibility of the printed hybrid hydrogels for various cell lines including stem cells was demonstrated.
For AC-magnetic field responsiveness, high resolution IR thermography confirmed that incorporated magnetic nanoparticles retain sufficient magnetic response to provide spatial temperature gradients for cell stimulus and for stimulus-responsive release. The advantages of spatial patterning of thermally active components will be described. Applications of DC-magnetic fields to physical stimulation of patterned magnetic gels will also be presented.
1. Zhang, X. et al., The Pathway to Intelligence: Using Stimuli-Responsive Materials as Building Blocks for Constructing Smart and Functional Systems. Advanced Materials 2019, 0 (0), 1804540.
2. Farahani, R. D. et al., Three-Dimensional Printing of Multifunctional Nanocomposites: Manufacturing Techniques and Applications. Advanced Materials 2016, 28 (28), 5794-5821.
3. Stolarczyk, J. K. et al., Nanoparticle Clusters: Assembly and Control Over Internal Order, Current Capabilities, and Future Potential. Advanced Materials 2016, 28 (27), 5400-5424.
The authors acknowledge support from Science Foundation Ireland (16/IA/4584 and 13/IA/1840).
1:45 PM - SB04.12.02
Digital Light 4D Printing of Bioinspired Hydrogels with Programmed Morphologies and Motions
Amirali Nojoomi1,Hakan Arslan1,Kyungsuk Yum1
University of Texas1Show Abstract
Living organisms use spatially controlled expansion and contraction of soft tissues to achieve complex three-dimensional (3D) morphologies and movements and thereby functions. However, replicating such features in man-made materials remains a challenge. Here we present a method named digital light 4D printing (DL4P) that encodes 2D hydrogels with spatially and temporally controlled growth (expansion and contraction) to create 3D structures with programmed morphologies and motions. This approach uses temperature-responsive hydrogels with locally programmable degrees and rates of swelling and shrinking. This method simultaneously prints multiple 3D structures with custom design from a single precursor in a one-step process within 60 s and is thus highly scalable. We suggest simple yet versatile design rules and the concept of modularity for creating complex 3D structures and a theoretical model for predicting their motions. We reveal that the spatially nonuniform rates of swelling and shrinking of growth-induced 3D structures determine their dynamic shape changes. We demonstrate shape-morphing 3D structures with diverse morphologies, including bioinspired structures with programmed sequential motions. This approach could potentially transform the way we design and fabricate soft engineering systems, such as soft robots, soft actuators, and 3D tissue structures.
2:00 PM - SB04.12.03
Polymer-Nanoparticle Hydrogels for Enhanced Delivery of Human Mesenchymal Stem Cells
Abigail Grosskopf1,Anton Smith1,Gillie Agmon1,Eric Appel1
Stanford University1Show Abstract
Stem cell therapies have emerged as a promising method for treating injuries and diseases in regenerative medicine, but delivering stem cells often requires invasive techniques and results in heterogeneous injections and poor cell retention at the injection site. Traditional cell delivery methods using liquid injections or surgical implants have limited the efficacy of these treatments. We have designed a novel injectable polymer-nanoparticle based hydrogel for effective delivery of human mesenchymal stem cells. This supramolecular hydrogel supported by dynamic hydrophobic interactions is capable of longterm 3D cell maintenance and retains injected cells for up to 10 days, twice as long as traditional delivery with liquid PBS injections. We uncover the fundamental hydrogel mechanical properties that enhance the entire cell delivery process. Through both in vitro and in vivo experiments, we demonstrate a scalable, synthetic, and biodegradable hydrogel with tunable mechanical properties that enables effective cell delivery. This shear-thinning and self-healing polymer-nanoparticle hydrogel also presents valuable opportunities in designing novel inks for applications in 3D bioprinting.
2:15 PM - SB04.12.04
Shape-Shifting Structured Lattices via Multi-Material 4D Printing
John Boley1,Wim van Rees2,Charles Lissandrello3,Mark Horenstein1,Ryan Truby4,Arda Kotikian4,Jennifer Lewis4,Lakshminarayanan Mahadevan4
Boston University1,Massachusetts Institute of Technology2,Draper Labs3,Harvard University4Show Abstract
Shape-morphing structured materials have the ability to transform a range of applications, from deployable systems and dynamic optics to soft robotics and frequency shifting antennae. Despite numerous advances, the integrated design and fabrication of shape-shifting structures that morph into complex three-dimensional (3D) shapes remains a challenge, owing to the difficulty of controlling the underlying metric tensor in space and time. Here, we exploited a combination of multiple materials, geometry, and 4D printing to create structured lattices that overcome this problem. We first produced printable inks composed of elastomeric matrices with tunable cross-link density and anisotropic fillers to control the material elastic modulus (E) and actuation capability via coefficient of thermal expansion (α). We then printed curved bilayer ribs in the form of lattice structures, in which the geometry of each rib is individually programmed to achieve local control over the metric tensor. Using multiplexed bilayer ribs composed of four materials, we can independently control extrinsic curvature and thereby encode a wide range of three-dimensional shape changes in response to temperature. As exemplars, we designed and printed flat lattices that morph into frequency-shifting antennae and a human face that demonstrate functionality and geometric complexity, respectively. Our inverse design and multi-material 4D printing method can be readily extended to other stimuli-responsive materials and different 2D and 3D cell designs to create scalable, reversible, shape-shifting structures with unprecedented complexity.
2:30 PM - SB04.12.05
Peptide/Graphene Hybrid Hydrogels as Potential 3D Injectable Cell Delivery Vehicle for Intervertebral Disc Repair
Cosimo Ligorio1,Jacek Wychowaniec1,Aravind Vijayaraghavan1,Judith Hoyland1,Alberto Saiani1
University of Manchester1Show Abstract
Cell-based therapies in particular have shown significant promise in tissue engineering with one key challenge being the delivery and retention of cells. As a result, significant efforts have been made in the past decade to design injectable biomaterials to host and deliver cells at injury sites. A recent strategy that has emerged for the design of increasingly functional hydrogels is the incorporation of nanofillers in order to exploit their specific properties to either modify the performance of the hydrogel or add functionality. The emergence of carbon nanomaterials in particular has provided great opportunity for the use of graphene derivatives (GDs) in biomedical applications. The key challenge when designing hybrid materials is the understanding of the molecular interactions between the matrix (peptide nanofibers) and the nanofiller (here GDs) and how these affect the final properties of the bulk material. For the purpose of this work, three gelling β-sheet-forming, self-assembling peptides with varying physiochemical properties and five GDs with varying surface chemistries were chosen to formulate novel hybrid hydrogels. First the peptide hydrogels and the GDs were characterized; subsequently, the molecular interaction between peptides nanofibers and GDs were probed before formulating and mechanically characterizing the hybrid hydrogels. We show how the interplay between electrostatic interactions, which can be attractive or repulsive, and hydrophobic (and π−π in the case of peptide containing phenylalanine) interactions, which are always attractive, play a key role on the final properties of the hybrid hydrogels. The shear modulus of the hydrid hydrogels is shown to be related to the strength of fiber adhesion to the flakes, the overall hydrophobicity of the peptides, as well as the type of fibrillar network formed. This work clearly shows how interactions between peptides and GDs can be used to tailor the mechanical properties of the resulting hydrogels, allowing the incorporation of GD nanofillers in a controlled way and opening the possibility to exploit their intrinsic properties to design novel hybrid peptide hydrogels for biomedical applications. [J. Wychowaniec et al. Biomacromolecules 2018, 19, 2731−2741]
Intervertebral disc (IVD) degeneration, a major cause of back pain, is a particularly relevant example where a minimally-invasive cellular therapy (injecatble hydrogel) could bring significant benefits specifically at the early stages of the disease, when a cell-driven process starts in the gelatinous core of the IVD, the nucleus pulposus (NP). Based the knowledge gained above we explored the use of graphene oxide (GO) as nano-filler for the reinforcement of FEFKFEFK (β-sheet forming self-assembling peptide) hydrogels. We confirmed the presence of strong interactions between FEFKFEFK and GO flakes with the peptide coating and forming short thin fibrils on the surface of the flakes. These strong interactions were found to affect the bulk properties of hybrid hydrogels. At pH 4 electrostatic interactions between the peptide fibres and the peptide-coated GO flakes are thought to govern the final bulk properties of the hydrogels while at pH 7, after conditioning with cell culture media, electrostatic interactions are removed leaving the hydrophobic interactions to govern hydrogel final properties. The GO-F820 hybrid hydrogel, with mechanical properties similar to the NP, was shown to promote high cell viability and retained cell metabolic activity in 3D over the 7 days of culture and therefore shown to harbour significant potential as an injectable hydrogel scaffold for the in-vivo delivery of NP cells. [C. Ligorio et al. Acta Biomaterialia in press DOI: 10.1016/j.actbio.2019.05.004 ]
3:30 PM - SB04.12.07
Electrochemical 4D Printing of Bimetallic Objects
University of Cambridge1Show Abstract
3D printing (additive manufacturing) is drawing more attention as a flexible manufacturing technology. In particular, Selective Laser Sintering (SLS) is a metal-based additive manufacturing technique that has been widely applied in medical, aerospace and motorsport applications. However, the essential parts of SLS system, such as high-power laser nozzle and metals powders, have high capital cost associated with the safety risks, which limit its wider application. In addition, most of the existing metal 3D printing systems can only print in a single material, which lack design flexibility. Concurrently, interest in 4D printed structures, which can react to environmental stimuli such as temperature, light, electrical and strain, is also growing due to the potential of creating objects with passive mechanisms and self-morphing characters. However, most 4D printed structures currently use polymer-based or hydrogel-based materials, which limits their mechanical strength and operating temperature.
Here, I present a novel multi-metal electrochemical 3D printer that can fabricate copper-nickel bimetallic with different architectures. Due to the mismatch in the thermal expansion coefficients, the mechanical deformation of printed bimetallic structures was programmed at temperatures up to 300 °C enabling tailored high-temperature responsive behaviour. Using a combination of scanning electron microscopy, optical microscopy, energy dispersive X-ray spectroscopy, X-ray computed tomography and electrical measurements, the morphologies of the printed structures were investigated. Moreover, electrochemical deposition of these metals create polycrystalline structures, achieving electrical conductivities that lie between that of nanocrystalline copper (5.41 × 106 S/m) and nickel (8.2 × 106 S/m). A tightly formed metal-metal boundary can be achieved, reducing delamination problems observed in other multi-material printing approaches. However, non-uniform convex cross-sections are created due to current density vibration. The work also explores different bimetallic structural designs and how modifications of this can generate different programmable structures with examples being a self-assembled “ICL”.
The author believes that this technique has broad and high impact applications due to the ability to process a range of materials and alloys, which can produce high temperature 4D structure and more importantly opens possibility for creating more intelligent structures and sensors at low cost and high safety. Other advantages include the fact that this process can be both additive and subtractive through reversal of potential, allowing for recycling of components through electrochemical dissolution.
3:45 PM - SB04.12.08
Patterned Hygroscopic Control of Four-Dimensional Prints of Silk Fibroin Protein
Xuan Mu1,David Kaplan1
Tufts University1Show Abstract
Four-dimensional (4D) printing of shape-morphing hydrogels is generally realized through patterning composite materials with contrasting properties (e.g., rigid vs. soft, responsive vs. non-responsive) or through control of crosslink density within photo-curable polymers. Here, we demonstrate a new strategy to print shape-morphing monolithic structures of silk fibroin protein by exploiting molecular assembly to pattern hygroscopicity. Hygroscopicity results in materials that expand and shrink upon absorption and removal of water, respectively, which has been found in natural and synthetic materials including paper, polycarbonate, wood, nylon as well as silk. Macroscopic deformation results from changes of hydrogen bonds between/within molecular chains and the transport of water molecules through nano- and micro-scale porous morphology. We used well-dispersed silk fibroin solution (~30 wt%) regenerated from B. mori. cocoons as the printing ink, which was then printed in layer-by-layer fashion on plain glass slides immersed in an aqueous inorganic salt bath. The bath was rationally designed to direct the assembly of silk fibroin molecules into hierarchical structures from beta-sheet crystals to nano-fibrils, to micro-filaments and then to 3D macro-prints. The phase transition of the protein ink from liquid to water-insoluble solid was accompanied by the removal of water into the salt bath; while water removal at the bottom/first layer (adjacent to the water-impermeable glass slide) was more difficult than later layers that are fully exposed to the aqueous bath. The residual water influenced the crystallinity and porous morphology of the assembled structures. FTIR and SEM identified the bottom layer with ~48% beta-sheet and micro-pores (~10 micrometer diameter) in contrast to 41% and nano-pores (~10 nm) for the later layers. There is a significant difference in the magnitude of hygroscopic strain of the filaments from the different layers. We empolyed the mismatch of the strain to transfrom a planar print into a range of Gaussian curvatures including positive (cone), zero (cylinder) and negative (saddle). Furthermore, full control over the transformation of planar two-layer rectangles into 3D helices was demonstrated, where the pitch and radius of the helix was dictated by filament interval and angle. In order to predict the transformations of the printed structures, a finite element analysis model was developed to simulate large hygroscopic strains under humidity changes using experimentally obtained hygroscopic coefficients and hyperelastic properties of silk fibroin. The numerical simulations were in good agreement with the experimental results, supporting the proposed mechanism of patterned hygroscopic control. The versatile and programmable transformations, as well as the simulations, should enable a range of biomedical applications and provide key insights into 4D printing of other hygroscopic materials.