Symposium F.SM02—Hydrogel Technology for Humans and Machines

Orthopaedic biomaterials for use as bearings against cartilage in diarthrodial joints face the dual challenges of being able to withstand high multiaxial loads while minimizing coefficient of friction and wear. High lubricity in aqueous conditions has been achieved with hydrogels such as poly(vinyl alcohol) (PVA), but mechanical properties of these hydrated polymeric networks have typically been inferior to native cartilage. Conversely, high mechanical properties can be achieved with other engineered materials but with increased cartilage wear. This study describes a novel biomimetic hydrated semi-interpenetrating network (IPN) based on poly(ether urethane) (PEU) that was previously implanted in a rabbit cartilage repair model¹. The frictional and mechanical properties compare favorably with native cartilage.

A tunable semi-IPN of PEU and a cross-linked polyelectrolyte network was synthesized. Similar to proteoglycans in hyaline cartilage, the polyelectrolyte caused the semi-IPN to swell in water, imparting the high lubricity of a hydrophilic polymer network, while the PEU imparted high stiffness and strength, resembling the collagen type II of cartilage. Upon completion of synthesis, the semi-IPN was a translucent, highly hydrated, qualitatively slippery material. The semi-IPN passed standard ISO 10993 biocompatibility testing.

The semi-IPN was evaluated for coefficient of friction (COF) using a pin-on-disk friction tester with ~1 MPa normal loading in aqueous conditions against a fused silica counterface, yielding a COF of < 0.05; typical cartilage COFs have been reported as <0.01-0.04². The mechanical properties were measured in tension, compression, tear, and shear in physiologically relevant conditions (simulated body fluid at 37° C) and compared to known properties of articular cartilage and PVA orthopaedic hydrogels. Compressive and tensile moduli at physiologic loads were > 40 MPa, stiffer than PVA orthopaedic hydrogels⁴ and considerably closer to the modulus of cartilage³ than traditional joint replacement materials like ultra-high molecular weight polyethylene (UHMWPE) and cobalt chrome alloys (CoCr). Tensile strength was > 30 MPa (cartilage: 3.75 MPa⁵), tear strength was > 40 N/mm (cartilage: 1.21 N/mm⁶), shear strength was > 20 MPa (cartilage: 7.25 MPa⁵), and the material did not fail in the measured compression range (>180 MPa; cartilage: 35.7 MPa⁷). By design the material strength exceeded that of native cartilage, in order to ensure long term performance without adversely impacting adjacent or opposing cartilage.

Hydrated semi-IPNs based on PEU and a polyelectrolyte network offer an attractive combination of mechanical strength, stiffness, and lubricity under physiologic loads. The semi-IPN properties, which closely mimic or exceed the high strength and low friction of native cartilage, provide a promising and novel platform for cartilage replacement applications.

1. Bichara DA; Unterman S; Schmidt MB. Orthopedic Research Society (2020 Annual Meeting).
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Contact lenses can be used as drug delivery systems because they are cross-linked, water-soluble, biocompatible hydrogels. Glaucoma is the second largest cause of blindness worldwide that increases the interocular pressure (IOP) of the eye. Topical eye drops of timolol is a common treatment that lowers IOP. The number of patients who become bilaterally blind every year is high due to the inefficiencies of eye drops and low patient adherence. In this study, three hydrogel-based contact lenses were analyzed on their uptake and release concentrations, reversibility, drug concentration profile over 12 hours, as well as their optical and mechanical properties. Synthesized molecular imprinted and soaked, non-imprinted, hydroxyethyl methacrylate (HEMA) based hydrogels resulted in having an uptake and release concentration dependent on the loading solution concentration it was left to soak in. Soaking Acuvue contact lenses resulted in having an uptake and release concentration independent of the timolol loading solution concentration. It released significantly higher concentrations than a daily dosage of timolol. All three hydrogel-based contact lenses successfully delivered timolol for 12 hours and could be reused up to six times. The synthesized HEMA hydrogels lacked in optical and mechanical properties that were to ensure comfort and prevent vision problems when used as a contact lens. As a result, further optimization is needed. Using contact lenses to deliver glaucoma medication has the potential to become a more efficient method of treatment that will increase patient adherence by eliminating barriers within glaucoma therapy created by eye drop medication.

In recent years, there’s an increase of study regarding 3D printing of soft materials, because of its importance for development of new technologies such as wearable electronic devices and artificial human organs, which require both non-rigid property and precise positioning. For 3D printing of soft materials study, it is required to choose a material which has enough viscosity but also can be easily extruded without clogging, and for that, pluronic is one of the most widely used materials. Pluronic is a thermo-responsive triblock copolymers consisting of poly(propylene oxide) (PPO) and poly(ethylene oxide) (PEO), as the hydrophobic center and hydrophilic side blocks respectively. This structure allows pluronic to form spherical micelles above its critical micelle temperature (CMT) within aqueous solution, which is suitable for 3D printing. Upon deposition on a substrate, by controlling the extruder and bath, pluronic can quickly change its phase, preventing the ink from flowing out of the intended position and retaining the desired 3D shape. In this study, pluronic F127 ((PEO)₉₉-(PPO)₆₅-(PEO)₉₉) is synthesized into pluronic F-dimethacrylate (FDMA) to prepare hydrogels for extrusion-based 3D printing. This work can be further developed to have 3D printed hydrogels with conductive property or controllable elastic modulus. The synthesis of FDMA is simple and it has the prospect for applications in various fields.

In addition to having non-toxic degradation products, being cytocompatible, and causing the formation of an extracellular matrix, fibrin, a major plasma protein, has been found to be highly suitable in supporting dental tissue formation and improving cell-dentin interactions[1]. This study sought to determine the effects of fibrin on the proliferation and differentiation of dental pulp stem cells, DPSCs, an investigation with potential applications in osteogenic regenerative therapy. Prior studies for in-vitro cultures of DPSCs directly on fibrin clots failed due to rapid fibrinolysis of the substrates prior to differentiation. Here we demonstrate the construction of a gelatin/fibrin scaffold, which is not enzymatically degraded at least during the 28 days required for DPSC differentiation. Furthermore, since gelatin is easily bioprinted it also offers an effective scaffold for fibrinogen, which is then rapidly cross-linked after extrusion, maintaining its shape. Gelatin-fibrinogen hydrogels were created using 9% w/v gelatin and 4 mg/mL bovine fibrinogen cross-linked by 2 different concentration of mTG (microbial transglutaminase) and 2units/ml thrombin, respectively. The gels were media exchanged and cells were cultured in osteogenic media, but without dexamethasone, the standard inducer of osteogenic differentiation. On Days 8 and 28, confocal microscopy indicated that strong tissue formation was occurring on both substrates. RT-PCR was performed at day 8 and 28 to measure the upregulation of genes associated with differentiation; ALP, COL1, and OCN. Even though this set of genes was upregulated on all samples, relative to cells plated on TCP controls, the levels for ALP and OCN for cells plated on the for gelatin-fibrinogen mixture were two and three times higher, respectively, than those for cells plated on pure gelatin confirming the regenerative potential of fibrin clots.

Modern medicine is seeking stronger composite materials for artificial bone graft applications that are both osteoconductive and exhibit high strength. Alginate-calcium phosphate (CaP) hydrogels have been studied as a potential material, but lack the strength required for artificial bone grafts. Here, we suggest using an alginate-gelatin dual-network embedded with magnetically-aligned CaP rods to significantly increase the overall strength of the material. CaP rods were prepared through hydrothermal precipitation and functionalized with iron oxide nanoparticles. These rods were incorporated into uncrosslinked dual-network solution and aligned under a magnetic field with constant heat and vibration. After alignment, the gelatin was thermally crosslinked at room temperature and the alginate ionically crosslinked in 10% calcium chloride solution. Tensile samples were analyzed using dynamic mechanical analysis. Preliminary results show superior mechanical strength in the dual network films compared to alginate- and gelatin-only hydrogels. The mechanical strength is further increased with higher concentrations of CaP rods. Alignment orientation also impacts hydrogel mechanics, with parallel alignment providing greatest strength and perpendicular alignment the greatest elasticity. The results of this study indicate that an osteoconductive alginate-gelatin hydrogel with high strength is possible with magnetically-aligned reinforcement and is a promising material for bone graft applications.

Thermal management is essential for living organisms and electronic devices to survive and maintain their functions. However, it has been challenging to develop a flexible cooling devices for flexible electronics or biological systems because conventional coolers are bulky and require rigid batteries. In nature, however, the skin helps to maintain the body temperature constantly by dissipating the heat through the perspiration. Inspired by nature, we introduce an artificial perspiration membrane which automatically regulates evaporation rate at water-air interface depending on temperature. This membrane consists of a valve structure and a rigid frame; the valve is made of silicone-coated thermo-responsive hydrogels and the frame is made of plastics. Those two components are stably bonded by copolymerization. By designing the shape of the valve and the mechanical constraint, we were able to control the area where evaporation occurs depending on temperature. As a result, the valves in the membrane open in a hot environment, which facilitates the evaporation of water, and the valves close in a cool environment, which suppresses the evaporation of water, mimicking cooling function of perspiration in a flexible manner. Our work shows the potential value of a bio-inspired, membrane-type, and automatic cooling device that can solve heat problems in artificial skin devices.
The thermo-responsive hydrogel is patterned with pinwheel-like shape and supported by backbone through copolymerizing at the interface to control the evaporation area depending on the temperature. The stretchable rubber is selectively coated to prevent the unintended evaporation through the hydrogel while securing the water path for swelling. Consequently, the water surface at open state is about 6 times greater than that of close state with fast transition rate (~1 s). The evaporation rate is automatically controlled depending on the temperature with 30% of evaporation reduction at lower temperature. Our study on a smart membrane that can automatically regulate cooling power without external power source may solve thermal problems in wearable or artificial skin devices.

Mesenchymal stem cell (MSC) delivery and subsequent differentiation into bone forming cells has promising implications for the future of bone repair. Use of hydrogel as a delivery vehicle is advantageous in order to enhance cell retention, and provide a scaffold to facilitate new bone growth. Here we describe a microporous injectable hydrogel for encapsulation of MSCs with the intent to improve proliferation and subsequent osteogenic differentiation. Physically crosslinked microgels are formed by thermal crosslinking of gelatin in a water in oil emulsion. Bulk scaffold formation involves chemical crosslinking of gelatin by nontoxic enzymatic reaction. Enzymatic crosslinking of gelatin provides prolonged strengthening of the bulk gel, and provides a covalent mechanism for tissue adhesion. A hydrated suspension of microgels and cells can be injected for noninvasive cell delivery, and the scaffold can crosslink in situ, encapsulating delivered cells in the pore space. This hydrogel provides an advantageous environment for MSC growth and differentiation due to the large interstitial space between microgels, which improved cell spreading and proliferation when examined by confocal microscopy, and improved osteogenic differentiation when examined using alizarin red S stain and high resolution micro computed tomography.

Brain aneurysms are focal, pathological dilations that mostly form at branch points of the cerebral vasculature. These weak-wall structures can rupture leading to hemorrhagic stroke with mortality and morbidity rates as high as 40% and 25%, respectively. More than 60% of aneurysms are currently treated with minimally invasive endovascular/interventional methods. Most of these methods involve the permanent implantation of metallic devices such as intrasaccular coils and meshes or endovascular flow diversion. These implants reduce blood flow velocity within the aneurysm and thus promote clot formation within the aneurysmal sac, which is converted to fibrous tissue over a period of several months. However, current devices show unfavorable primary outcomes in 20% to 30% of cases on average and success rates are substantially lower depending on aneurysm type and location. In this project, we discuss the development of an injectable, multi-functional, reverse thermo-responsive, in situ cross-linkable, shape-conforming, intrasaccular porous scaffold. This scaffold changes dynamically to enhance the associated wound healing process which follows obduration. The scaffold is engineered to work with the natural blood flow and promotes vascular remodeling and endothelialization followed by personalized biodegradation, at the end of the process, leaving no residue behind. This research program harnesses the unique behavior of a family of reverse thermo-responsive (RTR) polymers to generate a novel Biodegradable Intrasaccular Polymeric Device, displaying enhanced clinical performance. The aqueous solutions of these polymers display low viscosity at infa-physiological temperatures and are gels at 37 degrees. The device is an easily syringable, low viscosity multi-component aqueous solution comprising: [a] a cross-linkable RTR component that forms a robust and homogenously porous scaffold for controlled intrasaccular thrombosis, [b] a leachable RTR-displaying component acting as the porogen, [c] an iodine-rich radiopaque agent, [d] a polymerizable (RGD)-containing oligopeptide that will in situ co-polymerize with the other components, aimed at accelerating the generation of an endothelial cell layer at the aneurysm neck, [e] inclusion of basic Fibroblast Growth Factor (bFGF) in the cross-linked component to promote thrombus organization and intrasaccular fibrosis/remodeling, and [f] a cross-linkable oligopeptide containing the matrix metalloprotease (MMP)- degradable leucine-glycine motif that will be in situ co-crosslinked with the RTR components, to impart to the polymer device to degrade in a personalized, patient-specific manner, as a function of the healing process. This process represents a major step in treatment of aneurysms, which shortens optimize brain aneurysm treatment with short procedure times, require no chronic anti-platelet medications, promote endothelialization of the parent-vessel interface, enhance aneurysm ‘sac’ fibrosis, and degrade in a patient-specific manner to leave no trace of the pathology or the treatment, with lower costs.

*Authors 3-10 contributed equally to this work.
We gratefully acknowledge support from the Louis Morin Charitable Trust

[1]Taschner CA, Chapot R, Costalat V, Machi P, Courtheoux P, Barreau X, et al. Second-Generation Hydrogel Coils for the Endovascular Treatment of Intracranial Aneurysms: A Randomized Controlled Trial. Stroke. 2018;49(3):667-74.
[2]Sosnik A, Cohn D. Reverse thermo-responsive poly (ethylene oxide) and poly (propylene oxide) multiblock copolymers. Biomaterials. 2005;26(4):349-57.

In cardiac tissue engineering the incorporation of nanoparticles (NPs) such as plasmonic NPs, carbon nanotubes or magnetic particles was shown to improve the function of in vitro cardiac patches in terms of cell viability, electrical signal coupling, beat synchronicity, etc. [1,2]. Moreover, it has also allowed to locally deliver stimuli to cells and guide cell behavior, for instance, by heating of plasmonic NPs[3].

In this work, we created a smart scaffold capable of optically reporting cardiomyocyte activity in situ (electrical and contractile) by incorporating voltage-sensitive semiconductor quantum dots (QDs) in 2D scaffolds and 3D hydrogels.

We have characterized the fluorescence voltage sensitivity of Type I CdSe/ZnS QDs and pseudo-Type II CdSe/CdS rods, investigated in a controlled environment, under single and two photon optical excitation. Then, QDs were incorporated in 2D scaffolds of collagen nanofibers and used two-photon fluorescence microscopy to readout of the activity of cultured primary cardiomyocytes [4]. The method was validated in a pharmacological assay where the drugs epinephrine and blebbistatin were used for their combined chronotropic and inotropic effects. Finally, the concept is extended to 3D by incorporating QD-labeled collagen fibers in 3D hydrogel constructs.

[1] Baei, P. et al. Electrically Conductive Gold Nanoparticle-Chitosan Thermosensitive Hydrogels for Cardiac Tissue Engineering. Mater. Sci. Eng. C 2016, 63, 131–141.
[2] Yu, H. et al. Mechanically and Electrically Enhanced CNT-Collagen Hydrogels As Potential Scaffolds for Engineered Cardiac Constructs. ACS Biomater. Sci. Eng. 2017.
[3] Baffou, G. et al. Photoinduced Heating of Nanoparticle Arrays. ACS Nano 2013, 7 (8), 6478–6488.
[4] Jooken, S. et al. Quantum Dot-Functionalized Extracellular Matrices for in Situ Monitoring of Cardiomyocyte Activity. ACS Appl. Nano Mater. 2020.

Many efforts have been conducted to develop bioassays in point-of-care settings for rapid and convenient biomarker detection. Among them, the colorimetric-based system has been emerging due to the advantages in simple read-out through the naked-eye without requiring any expensive devices. However, it has still been challenging to simplify the labor-intensive multiple steps required to improve the limit of detection and remove the background color which may interfere with the detection signal.
Herein, we report a gelation-based bioassay mediated by a cascade reaction of two enzymes. We reasoned that biomarker-specific gelation can provide a detectable signal through the naked-eye even in the presence of the background color biospecimens such as blood and urine. Gelation is triggered by the quinone tanning reaction of catechol-conjugated polyethylene glycols via horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H₂O₂). Therefore, we coupled another enzyme, glucose oxidase (GOx), that produces the H₂O₂ depending on the concentration of glucose to initiate the HRP-mediated gelation.
In our system, parameters adjusting the gelation time include the concentration of enzymes (HRP and GOx), catechol content conjugated to the polymeric precursor, the concentration of polymeric precursor, and the pH. In the experiment using H₂O₂ as a positive control to glucose/GOx system, the gelation time dramatically decreased down to 1 minute as the HRP concentration increased up to 1 U/mL. In the HRP/GOx dual-enzyme system, 0.25 U/mL of HRP was sufficient to achieve successful gelation within 80 minutes with 10-100 U/mL of GOx in the presence of 10 mM glucose. The best conditions of other parameters for the fastest gelation were observed at 83% of catechol content, 5wt% of the precursor, and pH 7. Finally, as low as 16 mM of glucose was detectable through the naked-eye within 20 minutes of gelation time.
With the advantage of the cascade reaction of two enzymes, we expect improvement in the detection sensitivity. In addition, single-step glucose detection is allowed without requiring washing steps due to the enzymes’ intrinsic specificity.

Microcapsules can be used to monitor the local micro-environment in vivo, e.g., within the gastro-intestinal (GI) tract. For example, when molecular signals are released into the GI, the payload within the microcapsules could undergo a color change in response to the signal. While the nature of the signal is often the key piece of information in such experiments, the time at which the signal is released could be another vital aspect. To obtain information regarding time, there is the need for a gel-like material that could function like a ‘clock’ – i.e., exhibit systematic changes at regular time intervals.

Here, we report a simple ‘clock’ construct based on self-destructing structures embedded in an agarose gel. For this, we fabricate capsules of alginate crosslinked by Ca²⁺ and containing the enzyme alginate lyase. This enzyme severs alginate chains, thereby causing the capsule to degrade over a period of time. The higher the enzyme concentration, the lower the degradation time. Capsules with different concentrations of enzyme are embedded in an agarose gel to create our ‘clock’. Capsule degradation proceeds in a sequential manner, and visual inspection of the gel (i.e., the capsules that remain intact) reveals the time elapsed from the start of the experiment. To facilitate visual clarity, we embed colored or fluorescent nanoparticles in each of the capsules. Moreover, the degradation rate can be varied using pH, temperature, and other variables that affect the enzymatic activity. Variations of the above simple clock include: (a) one that is activated by an external trigger; and (b) one that locks-in the elapsed time at a particular juncture.

Over the last decade, three-dimensional bioprinting has offered great versatility to fabricate biomimetic volumetric tissues that are both structurally and functionally relevant to their native counterparts. The technology enables precise control over the composition, spatial distribution, and architecture of the bioprinted constructs, facilitating recapitulation of the delicate shapes and structures of targeted organs and tissues. This talk will discuss our recent efforts on developing various cytocompatible and cell-instructive bioink formulations, as well as their processing methods, for the fabrication of engineered tissues towards regenerative medicine and tissue model engineering applications, using a series of established or customized bioprinting strategies.

Hydrogels are among the first biomaterials expressly designed for their use in biomedicine. However, state-of-the-art applications of hydrogels are severely limited because of their mechanical properties. Most hydrogels are either too soft or too brittle to be used for load-bearing applications. To overcome this shortcoming, double network (DN) hydrogels composed of two interpenetrating polymeric networks have been introduced. These DN hydrogels are composed of a highly crosslinked network, the filler, responsible for the stiffness of the hydrogel and a second loosely crosslinked one, the matrix, that regulates the toughness of the material. Despite this great improvement in mechanics, composition and structural complexity found in soft natural tissues remain yet to be matched. Indeed, soft natural materials possess locally varying compositions and structures that are well-defined over many length scales. By contrast, synthetic hydrogels typically have an ill-defined microstructure and their composition is most often homogeneous. To obtain a better structural control, we introduce a novel 3D printing approach to fabricate strong and tough soft materials, namely double network granular hydrogels (DNGHs). This is achieved with an ink composed of microgels that are swollen in a monomer-containing solution. Upon printing and post-curing, the monomers are converted into a percolating network, yielding a solid DNGH. These DNGHs possess mechanical properties that are superior to reported additive manufactured hydrogels. In this work, we demonstrate that this technique enables printing macroscopic strong and tough objects with a high shape fidelity. Because this new technology employs a microgel-based ink, it significantly extends the choice of materials that can be additive manufactured. Moreover, the modularity of the jamming approach allows for the combination of different ink in the same printing process, resulting in mechanically robust stimuli responsive structures.

Over the last few decades, living cells have been employed as factories to make organic molecules, polymers, drugs, and fuels. Lately, living cells are being engineered to make materials and/or to modulate its properties, giving rise to an exciting field of Living Materials. Earlier work has shown that engineered living materials (ELMs) can bind to nanoparticles, catalyze reactions, and modulate conductivity amongst others.

Herein, we present a versatile strategy for the fabrication of living hydrogels directly from the bacterial culture by a simple filtration protocol. This hydrogel comprises of E. coli embedded in an extracellular matrix of engineered protein fibers. Genetic programming enables the hydrogels to be customized to interact and adhere to different tissues of the gastrointestinal tract. The designed mucoadhesive and anti-inflammatory hydrogels can be sprayed directly in the gut serving as an innovative wound healing strategy for the gut lumen.

By genetic engineering, we have also developed a functional microbial ink for 3D printing of living materials. This microbial ink is produced from engineered bacteria and can also be embedded with desired microbes to enable the printing of complex 3D architectures having various functions like sensing and sequestration.

Thus, we demonstrate the very first examples of microbial ink for 3D printing and the biomedical application of living materials. This unique platform of genetically programmable living hydrogels provides unprecedented opportunities to harvest the characteristics of living systems and thereby enables advanced applications of living materials.

Bioinks are hydrogels that have the ability to encapsulate cells and promote their proliferation, there are compound and hybrid bioinks of the following natural materials, synthetic polymers, bioceramics, metallic nanoparticles.
Composite bioinks are materials where their chemical structure and properties are combined in homogeneous way, otherwise, the hybrid bioinks have a chemical structure and properties combined in heterogeneous way, even in some hybrids bioinks, it is possible to observe different phases of this components.
At use gelatin/siloxane hybrid material in a room temperature, is possible to observe the organic (gelatin) and inorganic (siloxane) phase which is a temendous advantage. It is important to remark the presence of these phase offers thermomechanical properties that facilitate its funcionalization as bioink.
Siloxane is a direct derivate of silicon dioxide gel that is biocompatible and non - cytotoxic, properties that allows cell culture deposition and encapsulation, gelatin is a material derived from collagen which consist of a biopolymer of three aminoacids (arginine, glycine and lysine).
The functionalization of siloxane and gelatin by means of magnetic stirring allows the interaction of the amine groups (NH⁺) of gelatin and the hydroxyl groups (OH^-) of the siloxane.
The lost of water through the oxidation of the siloxane allows the modulation of thermomechanical properties of the gelatin/siloxane hybrid material, through physical treatments such as UV radiation and heat treatments in the range of fifty degrees centigrade (50C) to seventy degrees centigrade (70C), forming the siloxane bonds that improve the termomechanical properties of the material such viscosity and mechanical compression.
The gelatin/siloxane hybrid material possesses a viscosity that can be modulated by heat treatments in the range of thirty-two degrees centigrade (32C) to forty-two degrees centigrade (42C).
The viscosity of the gelatin/siloxane hybrid material is related to the concentration of dispersed siloxane particles.
This relationshio permit that at temperature in the range of four degrees centigrade (4C) to fifteen degrees centigrade (15C), the material reticulates by forming fibers that help maintain the fidelity and mechanical properties necessary to use the gelatin/siloxane hybrid material as bioink.
The aforementioned thermomechanical properties of the gelatin/siloxane hybrid material provide the support of being used as bioink. The gelatin/siloxane hybrid material let the cultivation of various cell lines such as: (carotid artery cells, liver, myocytes, cardiomyocytes amog others).
In function on its thermomechanical properties. The degradation of siloxane inhibits certain enzymes in bacterial metabolism that generate antibacterial properties.
3D bioprinting is a technique for biofabrication of three - dimensional structures thtat, through layered printing technology, allows manufacture constructs for the depost or seeding of cell cultures. The BIO X bioprinter (Cellink®) is a bioprinter with a resolution in the range of 10 to 100 µm depending on the bioink used ad the printing syringe nozzle. Is one of the most user - friendly bioprinters on the market, in addition to allow the use of composite and hybrid bioinks depending on the printing paramters (nozzle size, applied pressure, printing speed, head and print bed temperature), however, bioprinters are highly sophisticated and precise equipment, therefore, to determine the printing parameters of a bioink it is imperative to perfom mathematical analysis.
In conclusion, this work deals with the development of a bioprinting process specifically of the gelatin/siloxane hybrid material that, thanks to the matjematical model used, generates a better mechanical perfomance of the printed constructs with the assistance of the BIO X bioprinter (Cellink®) and provides a look to the futures with the first tests of a bioprinter that combines extrusion and injection technology.

In mussels, the adhesive proteins that are instrumental for attachment to wet surfaces are known to contain high levels of 3,4-dihydroxy-L-alanine (DOPA), often located adjacent to amino residues such as lysine (Lys). The special synergistic relationship between catechols and amines is a subject of high interest, not only for understanding native proteins but also for informing the design of bioinspired polymer systems. Other research groups have shown that catechol and amine functional groups act synergistically to enhance adhesion at wet surfaces, however reports of catechol-amine interfacial phenomena on a single molecule level have been limited. In this talk we will describe single molecule force spectroscopy (SMFS) measurements that are providing new insights into interactions between Lys-DOPA peptides and various surfaces. Of particular interest is the impact of chemical composition (DOPA and Lys), peptide length and topology (i.e. distribution of adhesive elements along a polymer) on interfacial adhesion to a wet substrate. The results may inform the future design of novel polymer adhesives, including adhesive hydrogels, pressure sensitive adhesives and high-strength thermoset adhesives.

Marine mussels secrete adhesive proteins that enable these organism to anchor themselves to various substrate (i.e., ship hull, rock) in a rough, intertidal zone. These mussel foot proteins contain a unique amino acid, L-3, 4 dihydroxyphenylalanine (DOPA), that is responsible for strong interfacial binding and curing of the proteins. The catechol side chain of DOPA is capable of participating in various stimuli responsive, reversible interactions, dictated by its oxidation state. In this presentation, I will describe our efforts in utilizing these interactions in designing various types of smart biomaterial. We have incorporated catechol-metal ion coordination bond to design hydrogel actuators that can fold into various 3-dimentional shapes. We have also utilized catechol-boronic acid complexation chemistry to design moisture-resistant smart adhesive with tunable adhesive properties. Most recently, we demonstrated the feasibility of using applied electricity to directly deactivate catechol-based adhesive that is bonded to a surface.

Reliable functions of bioelectronic devices require conformal, stable, and conductive interfaces with biological tissues. Integrating bioelectronic devices with native tissues usually relies on physical attachment or surgical suturing. Whilst these conventional methods face challenges such as non-conformal contact, unstable fixation, tissue damage and/or scar formation. Here we present a new class of bioadhesive electronic devices capable of compatibly and robustly integrating with various wet dynamic tissues, offering a promising solution beyond suturing and physical attachment to address the aforementioned challenges. The bioadhesive electronics are enabled by a new nanocomposite interface that can provide rapid (adhesion formation within five seconds), robust (interfacial toughness over 400 J m^-2), and on-demand detachable adhesion of bioelectronic devices on diverse wet tissues. The nanocomposite interface is electrically conductive (conductivity over 2.6 S m^-1) to allow bi-directional bioelectronic communications. We demonstrate applicability, mechanical and electrical stability, biocompatibility, and bioelectronic recording and stimulation functionalities of the bioadhesive electronics based on ex vivo porcine and in vivo rat models. This study provides a new powerful platform for diverse bioelectronics to address the long-standing challenges in human-machine interface.

Tools to close and repair wounds in our body are the first set of medical devices in human history. Despite the long history even started from the pre-historic use sutures, the standard care to close wounds still mostly rely on the traditional methods such as sutures and surgical staplers. These old standard cares have faced numerous lingering challenges including slow or complex procedure, leakage, and tissue damage with a huge cost to our society: each year, over millions of people suffer and perish due to the leakages of sealed incisions of organs, failures of prompt hemostasis, and chronic open wounds. Considering the fact that how the entire world has been suffered from the less than 1M death toll by the COVID-19, the degree of the clinical and societal burden from the limitations of current tissue closure and repair technologies is startlingly grave.

Tissue adhesives including tissue sealants and hemostatic agents have been the most recent technologies to address these challenges. However, translational benefits of the tissue adhesives in clinical applications have still been in the nascent state due to the long list of limitations of existing tissue adhesive technologies including 1) slow adhesion formation, 2) weak bonding, 3) low biocompatibility, 4) poor mechanical match with tissues, 5) incompatibility to body fluids like blood, 6) lack of triggerable on-demand detachment, 7) lack of programmable modulation of wounded tissues, and/or 8) poor compatibility to emerging surgical techniques such as minimally invasive surgeries (MIS). In this talk, we will introduce our set of recent advances to translational tissue adhesive technologies based on various yet highly synergistic multi-functional bioadhesive platforms to address all of the abovementioned limitations. We will first briefly summarize the unmet clinical demands in existing tissue adhesives with associated scientific backgrounds for the mechanistic source of the challenges. Then, we will introduce our multi-functional bioadhesive platforms to satisfy the unmet clinical demands with corresponding clinical applications that we are exploring with collaboration with leading clinical experts.

Methods for tissue sealing and repair in minimally invasive surgery (MIS) represent a significant challenge in the shift toward less invasive procedures. Traditional surgical sutures and stapling devices are often difficult to maneuver precisely in MIS, and these pointwise modalities of sealing can cause tissue damage and lead to anastomotic leakage. While tissue adhesives offer the potential to overcome these limitations, existing adhesives have significant drawbacks; for example, they can be easily washed out in dynamic physiological environments, are prone to fouling in the presence of blood and body fluids, exhibit slow and/or weak adhesion to wet tissue, and may induce unfavorable inflammatory responses. Here, we propose a novel multifunctional bioadhesive designed to achieve controllable tissue adhesion in diverse physiological environments. The bioadhesive takes the form of a conformable patch and is realized by a synergistic combination of three functional layers: 1) a hydrophobic liquid overlayer for protection against blood and body fluids, 2) a micro-textured bioadhesive layer for rapid and robust pressure-triggered adhesion, and 3) a zwitterionic anti-fouling layer for mitigation of foreign-body response and postoperative adhesion formation. The patch can be adapted to integrate with existing MIS tools, giving it the potential to advance a wide range of surgical procedures.

Impaired wound healing capability and consequent chronic wounds such as diabetic foot ulcers (DFU) are devastating complications in diabetic patients with rapidly growing clinical and economic burdens in aging societies, recording over 750,000 new DFU each year. Furthermore, significant clinical outcomes including lower extremity amputations are readily induced, resulting in the total annual cost of treatment of DFU and amputations at over 11 billion dollars. Given the rapidly growing patients across the world and the deleterious economic costs including a critical reduction in quality of lives, the treatment of diabetic wounds is one of the major current and future clinical challenges in need of effective solutions.

Despite various therapeutic strategies including several skin scaffolds and growth factor-based treatments that have been introduced and clinically tested for treatment of DFU in the last few decades, their benefits are rather limited as more than 50% of treated DFU patients fail to respond. This lack of effective treatment along with the gravity of the problem highlights the critical importance of developing new therapeutic solutions for diabetic wound healing.

Mechanical modulation of wounded or scarred skin has been a promising strategy to repair and remodel healthy skin in both animal models and human clinical trials. Given the previous animal studies indicating the reduced degree of contractibility of the wound as one of the sources of impaired wound healing in diabetes patients, such mechanical modulation is an attractive treatment route for diabetic wounds. However, the potential therapeutic benefits of the mechanical modulation approach have not been well investigated for chronic wounds such as DFU due to several technical limitations. Existing wound dressings and bandages for mechanical reinforcement or stimuli lack capabilities to 1) form rapid and robust adhesion on wet wounded skin and 2) precisely program mechanical contraction, limiting their use only for passive mechanical coverage, uncontrolled contraction, and/or fully closed wounds. These limitations have prevented the use of a mechanical modulation approach for chronic wounds such as DFU, leaving this potential therapeutic strategy untapped.

In this work, we report a strain programmable bioadhesive patch capable of rapid and fully programmable contraction and stress remodeling of wet wounded skins as a promising therapeutic platform for chronic diabetic wounds. The strain programmable bioadhesive patch synergistically combines a novel hydration-based shape-memory mechanism and the dry-crosslinking mechanism to simultaneously achieve rapid, robust, and on-demand detachable adhesion as well as predictable mechanical modulation when on wet wounded skin tissues. The strain programmable bioadhesive patch takes the form of a thin flexible film consisting of non-adhesive elastomer backing in the rubbery state (Young’s modulus ~ 1 MPa) and a dry bioadhesive in the glassy state (Young’s modulus ~ 5 GPa) with the programmed strain. Once hydrated by the native physiological fluids or moisture from the wounded tissue, the patch rapidly and robustly adheres to the underlying tissue by the bioadhesive while releasing its programmed strain to provide mechanical contraction to the wound.

To validate the proposed strain programmable bioadhesive patch and its efficacy on diabetic wound contraction and healing, we have performed systematic mechanical analysis (mechanical properties, adhesion performance, theoretical and FEM-based framework for predictable strain programming and mechanical modulation of a wound), in vitro and in vivo biocompatibility, and in vivo diabetic wound healing based on ex vivo porcine and in vivo diabetic mice models. The current study not only provides a promising solution for the treatment of chronic wounds but also offers insights into the development of technologies for programmable mechanical modulation of biological tissues.

Ostomies are digestive and excretory surgeries where waste is redirected to the outside of the abdomen, requiring a bag to catch excretion. Current methods use adhesives to create adhesion for 24-hour usage of the ostomy bag. However, current adhesives are weak and unstable, and often lead to leakages of ostomy effluents resulting various clinical complications including irritant dermatitis and infection. Despite these challenges, no commercially-available product can provide strong enough adhesion nor mechanical softness to prevent skin damage from ostomy leaks. In this work, we introduce a hydrogel ostomy adhesive (HOA) made from a tough double-network hydrogel based on polyacrylamide and sodium alginate that can be strongly adhered onto the skin for over 24 hours and prevent leaks by maintaining fluid-tight sealing against regular bodily movements. The adhesion of HOA to abdominal skin is achieved by the topological adhesion formed by a biopolymer chitosan solution. The HOA’s capability to form robust adhesion of ostomy bag is demonstrated based on ex vivo porcine skin and in vivo human skin in comparison with existing commercially-available ostomy bag adhesives.

This talk will present studies from our lab on the electrically induced adhesion of hydrogels to various soft matter. The basic phenomenon involves crosslinked acrylate hydrogels made with either anionic or cationic co-monomers. 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) within an electric field of ~ 2-4 V/ mm, 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 gel strips with gels of various geometrical structures made using charged biopolymers such as chitosan or alginate. The same electro-adhesion works in resealing punctures in gel tubes thereby preventing gas and liquids from leaking out of these punctured structures. As an extreme case, two severed pieces of a tube can be stuck back together using a gel strip that spans both cut segments. In turn, electro-adhesion can also be applied for the pick-up and drop-off of soft cargo, and for the sorting of small cargo. Most interestingly, the same phenomenon also works with certain animal and plant tissues – that is, we show that cationic gels can be electro-adhered to these tissues. We thereby demonstrate that cuts or tears in tissues can be electro-sealed using gel strips.

Dynamic covalent chemistry has emerged as an elegant molecular design strategy to engineer functional polymer networks that combine advantageous properties of both chemically and physically cross-linked materials. Dynamic covalent networks (DCvNs) are increasingly used in advanced materials design with applications ranging from recyclable thermosets to self-healing hydrogels. However, the relationship between the underlying chemistry at the junctions of DCvNs and their macroscopic properties is still not fully understood. In this presentation, we will outline a robust framework to predict how complex network behavior in DCvNs emerges from the chemical landscape of the dynamic chemistry at the junction. We use ideal dynamic covalent boronic ester-based hydrogels as model DCvNs. We will describe physical models that explain how viscoelastic properties, as measured by shear rheometry, are linked to the molecular behavior of the dynamic junction, quantified via fluorescence and NMR spectroscopy and DFT calculations. Additionally, shear rheometry is combined with Eyring Transition State Theory to quantify the kinetics and thermodynamics of network rearrangements, enabling a mechanistic understanding including preferred reaction pathways for dynamic covalent chemistries. We apply this approach to corroborate the ‘loose-bolt’ postulate for the reaction mechanism in Wulff-type boronic acids. These findings, grounded in molecular principles, advance our understanding and rational design of dynamic polymer networks, improving our ability to predict, design, and leverage their unique properties for future applications. We will also discuss applications of these materials for the thermal stabilization of biologics and as tunable viscoelastic materials.

Living tissues show an extraordinary adaptiveness to strain, which is crucial for their proper biological functioning. The physical origin of this mechanical behaviour has been widely investigated using reconstituted networks of collagen fibres, the principal load-bearing component of tissues. However, collagen fibres in tissues are embedded in a soft hydrated polysaccharide matrix which generates substantial internal stresses whose effect on tissue mechanics is unknown. Here, by combining mechanical measurements and computer simulations, we show that networks composed of collagen fibres and a hyaluronan matrix exhibit synergistic mechanics characterized by an enhanced stiffness and delayed strain-stiffening. We demonstrate that the polysaccharide matrix has a dual effect on the composite response involving both internal stress and elastic reinforcement. Moreover, the matrix has a pronounced effect on fracture of the networks, leading to enhanced toughness and a transition from brittle to ductile behaviour. Our findings elucidate how tissues can tune their strain-sensitivity over a wide range and provide a novel design principle for synthetic materials with programmable mechanical properties.

[1] F.Burla, J. Tauber, S. Dussi, J. van der Gucht, G.H. Koenderink, Nature Physics, 15, 549 (2019)
[2] S. Dussi, J. Tauber, J. van der Gucht, Physical Review Letters 124 (2020), 018002
[3] F. Burla, S. Dussi, C. Martinez-Torres, J. Tauber, J. van der Gucht*, G.H. Koenderink, PNAS 117 (2020), 8326

Interest in hydrogels over the past couple of decades has exploded for a wide range of biomedical applications, including drug delivery, and tissue engineering.¹ There is a huge interest in building these supramolecular structures from non-covalent interactions, e.g. hydrogen bonds, host-guest interactions, which provide an easy tailoring of dynamic properties, impart shear-thinning and thus injectability and self-healing, making them more amenable to biomedical applications.
Our group focuses on harnessing and understanding simple gelation processes in materials that come from renewable sources or are easily accessible. We exploit hybrid gelation processes to the cross-linking process,² spontaneous self-assembly in mixtures of modified polymers and surfactants,³ formation of pseudopolyrotaxanes with cyclodextrins,⁴ and thermally-triggered gelation.⁵ In this talk I will present some of our recent work on self-assembled gels and in particular how we use small-angle neutron scattering to elucidate the spatial organisation of the networks that sustain the rheological properties, and ultimately build towards a rationale for hydrogel formulations.

[1] C. A. Dreiss (2020) Curr. Opinion Colloid Interface Sci. 48, 1; C. Salzlechner et al. (2020) Adv. Healthcare Mat. 9, 4, 1901134; da Silva & Dreiss (2016) Polym. Int. 65, 268
[2] M.A. da Silva et al. (2017) J. Pol. Sci. B. 55, 1850; M. A. da Silva (2015) Biomacromolecules 16, 1401; M. A. da Silva et al. (2015) Biomacromolecules 16, 1401.
[3] N. Zoratto et al. (2019) J. Colloid Interface Sci., 556, 301
[4] M. Serres-Gómez et al. (2018) Langmuir, 34, 10591
[5] J. Puig-Rigall et al. (2017) J. Colloid Int. Sci. 524, 42

Understanding and tailoring the self-assembly of supramolecular moieties is a challenging subject with potential implications in materials engineering and biological function. Here we discuss two problems associated with the viscoelastic properties of (i) hydrogel mixtures due to competitive interactions and (ii) organogels due to the presence of traces of humidity.
Concerning the former, we investigated a class of binary hydrogels made by mixing fibrillar supramolecular polymers that are formed from two compounds: 1,3,5-benzene-tricarboxamide decorated with aliphatic chains terminated by tetra(ethylene glycol) (BTA) and a 20 kg/mol telechelic poly(ethylene glycol) decorated with the same hydrogen bonding BTA motif on both ends (BTA-PEG-BTA). We found that the respective single-compound-based supramolecular systems form very different networks which exhibit drastically different rheology. More strikingly, mixing the compounds results in a non-monotonic dependence of modulus and viscosity on composition, suggesting a competition between interactions of the two compounds, which can then be used to fine-tune the mechanical properties.
The latter problem concerns the self-assembly of supramolecular moieties in organic solvents which is affected by the presence of trace amounts of water in the monomeric state that induce competitive association and change the helicity of the assembled structure. We investigated an organogel in dodecane (biphenyl tricarboxamide, BPTA) and found that water affects the self-assembled structure by changing the persistence length and contour length of the fiber. The content of water in the fiber changed with temperature, bequeathing the linear and nonlinear viscoelastic properties with unusual temperature responsiveness. For instance, as the temperature increased from 15 to 35^oC, the relaxation time of the system varied non-monotonically with temperature. This stems from the fact that the system loses its reversible and dynamic character for temperatures above 35^oC where water does not mediate the association of BPTA units.
These findings are discussed in the context of existing theories of living polymers and of the perspective of designing gels with desired and tunable properties.

Work in collaboration with E. Vereroudakis (Crete), N.J. Van Zee (ESPCI, Paris), E. Del Gado (Georgetown) and E.W. Meijer (T. U. Eindhoven).

Aqueous droplets dispersed in fluorinated oils have found a wide variety of applications as biomimetic compartments for the isolation and analysis of cells and biomolecules. Advances in microfluidic manipulation of emulsion drops has enabled biological assays and diagnostics on the single cell and single molecule level at high throughput. Despite the significant advancements in the field of droplet microfluidics, some challenges remain. The stability of especially large drops over 50 microns in diameter is a key issue for applications involving long incubation periods necessary for cell proliferation or organoid growth, as well as thermal stresses experienced in thermocyling for polymerase chain reaction (PCR). Here we report our recently developed approach for stabilizing water-in-fluorocarbon emulsion drops with biocompatible interfacial films that contain a water-facing hydrogel and an oil-facing fluoropolymer that are cross-linked with dynamic covalent bonds. We combine fluorocarbon-soluble random copolymers that contain boronic acid moieties with biocompatible and hydrophilic polymers dispersed in microfluidics-derived water-in-fluorocarbon emulsion droplets. The dynamic covalent chemistry of boronic acids enables the formation of an amphiphilic interfacial thin film around the drop without the use of charged species that often inhibit or interfere with biologic functionalities such as enzyme activity. The amphiphilic interfacial film contains an inert polyol hydrogel facing the water drop and a highly fluorinated outer layer, providing armor to coalescence even in surfactant-free environments. We demonstrate the successful application of our armored droplets for in-drop (RT-)PCR with repeated thermocycling to 96 °C without drop coalescence or inter-drop diffusion even for drops as large as 200 microns, as well as the expansion of cells in 375 micron-sized drops incubated for 96 hours. The strength of the interfacial film is tunable by the choice of complexing polymer and copolymer composition. Our strategy of oil-soluble, boronic acid-containing copolymers for interfacial film formation and droplet stabilization is transferrable to water-hydrocarbon emulsions. Furthermore, tunable adhesive strength between the armored drops enables additive drop assemblies, producing filaments of aqueous microdroplets that are of interest to the hierarchically shape-guided growth of organoids and other cell colonies.

Many biomaterials possess unique structures that result in anisotropic mechanical properties, along with high strength, toughness, and water content. Applying the double network principle to develop tough hydrogels that possess these features with different polymer chemistries is important for the potential application of hydrogel materials. Synthesis of the two interpenetrating networks with contrasting structure and physical properties required for double networks usually involves a two-step polymerization process. First, the sacrificial network is fabricated, followed by the stretchable, weak network. In this work, we present a new method to synthesize tough double network hydrogels by post-physical crosslinking of linear, semi-rigid polyelectrolytes entrapped in a chemically crosslinked neutral network. This has been achieved through a one-pot polymerization method. Owing to their semi-rigid structure, poly(2,2’-disulfonyl-4,4’-benzidine terephthalamide) (PBDT) can form a brittle physical network above their overlap concentration in multi-valent ZrCl₂O ion solutions without macroscopic phase separation, within the flexible neutral network. The double network hydrogels thus prepared exhibit high modulus (~1.7 MPa), strength (~1.3 MPa), fracture strain (~7.3), and strain energy density (~5.9 MJ/m³), while containing over 80% water. These materials also exhibit modest self-healing ability (~51% after 30 minutes), demonstrating an additional benefit of a physical sacrificial network. Furthermore, applying pre-stretch prior to physical crosslinking allows for the fabrication of an oriented sacrificial network. The anisotropic hydrogels demonstrate a Young’s modulus anisotropy ratio of close to 3. The method presented here is simpler than the conventional two-step polymerization of traditional double network hydrogels and could be applied to develop tough hydrogels from rigid polyelectrolytes, including biopolymers such as DNA, HA, and chondroitin sulfate.

Ionic skin devices aim to mimic their biological counterparts for wearable devices and soft robotic applications by sensing touch due to a capacitive change upon deformation. Commonly, salts are added to hydrogels to create ionic conductors that are supported by mechanically compliant polymer networks for these devices. However, hydrogel systems are often unstable with respect to liquid evaporation and can require additional chemical crosslinks to improve gel mechanical stiffness and toughness.
Our group recently demonstrated gelatin-supported deep eutectic solvent (DES) gels using a 1:2 molar ratio of choline chloride (ChCl) and ethylene glycol (EG) as nonvolatile gel electrolyte alternatives. Compared to a hydrogel with the same gelatin content (22 wt.%), the DES gel demonstrated remarkably improved stretchability (fracture strain improved from 40% to 320%) and toughness (improved from 2.1 to 133 kJ/m³). As these gels were supported only by noncovalent cross-links formed via gelatin self-assembly (e.g. triple helices), there was a clear synergistic effect of both ChCl and EG on the gelatin scaffold to improve DES gel mechanical properties relevant to ionic skin applications. However, there is still a need to better understand how the solvent dictates in situ gelation.
In this work, we probe the inherent interactions between the solid and liquid components within these gels by exploring the effects of the organic hydrogen bond donor (HBD) of the DES as well as coformulation with 25 mol% water on the resulting gelatin self-assembly. These gel electrolytes were characterized to determine their tensile properties, ionic conductivities, and thermal transitions in order to probe interactions between ChCl, HBD, and water and the gelatin scaffold.
We have observed that varying the HBD identity within DES/water mixture gels enables tuning of the Young’s modulus by up to a six-fold increase: from 7 kPa (1,2-propanediol) to 42 kPa (glycerol) for a fixed gelatin content (20 wt.%). Additionally, DES/water mixture gels exhibit notable improvements in toughness and ionic conductivity versus their “dry” DES gel counterparts. Toughness was increased from 23 to 68 kJ/m³ for ethylene glycol-based gels and ionic conductivity increased from 3.3 to 5.2 mS/cm. Similar improvements to toughness and conductivity were found for glycerol-based DES gels, with water addition increasing gel toughness from 46 to 198 kJ/m³ and ionic conductivity from 0.9 to 1.2 mS/cm.
The results of this work demonstrate that water-in-DES mixtures can synergistically improve ion transport and mechanical properties within DES/water mixture gel electrolytes, and that proper materials selection of the liquid electrolyte and polymer scaffold system can lead to greater tunability of gel properties relevant to ionic skin device applications.

Diverse soft metamaterials have been developed for energy-absorbing, tunable thermal expansion, soft actuator, etc. Although various functional properties of soft metamaterials have been investigated, their fatigue properties have not been studied yet, which hinders the translation of soft metamaterials into real applications. With 3D printing techniques, we control the geometrical parameters of soft metamaterials. Fracture tests and simulations are conducted to measure the S-N curve of a single printing filament and fatigue threshold of 3D printed soft metamaterials. We show that the fatigue threshold of soft metamaterials is linearly proportional to the fiber's diameter and strain energy density limit, but independent of its length. Constitutive relation of the materials and geometrical shapes determine the prefactor of such proportion relations. The results are intrinsically different from the classical Lake-Thomas theory for polymer networks, leading to a generalized theory for predicting soft metamaterials' fatigue threshold. The capability of the theory correlating the fatigue property of a single filament and entire topological networks is critical for the design of durable soft metamaterials. This theory inspires us to manufacture sinusoidal structure metamaterials, whose fatigue threshold increase dramatically.

Neural tissues are extremely soft with kPa-range modulus. Hydrogels offer a unique opportunity to design neural interfaces with biomimetic mechanical properties. Some designs which utilize hydrogels either as coating or bulk material, such as penetrating intracortical probes, require de-hydration of the hydrogel before the time of implantation to prevent any buckling during insertion and to minimize the hydrogel delamination due to shear forces. Once inserted into the brain the hydrogel absorbs moisture from the tissue, swells and provides a tissue-like interface.

We report on the re-swelling process and assess the mechanical properties of the hydrogel in as-prepared and post re-swelling conditions, comparing thermal and freeze drying as de-hydration methods. We studied polyacrylamide (PAAm) hydrogel with increasing monomer concentrations (3 to 6% AAm), which correspond to shear storage moduli (G’) in the 120 to 750 Pa range. We found that the recovery of G’ and of the swelling capacity depends on the initial composition of the hydrogel. Following either thermal or freeze-drying process, the softest hydrogel (3% AAm) displays only 40% swelling capacity recovery and a 3.5 times increase in storage modulus, compared to its initial properties. Stiffer hydrogels were found to be less sensitive to the de-hydration process with a 2 to 2.8 G’ increase factor.

Next we studied the re-swelling kinetics and normal forces associated to the process, both in free and constrained swelling scenario (mimicking the implant-tissue interface). Finite element simulation extended the analysis to help quantify the mechanical stresses that are being exerted on the neural tissue during the re-swelling stage. Preliminary results indicate that these stresses may reach up to several tens of kPa for a 100μm thick hydrogel coating, being applied on the surrounding during a constrained re-swelling process of a 300 Pa hydrogel.

These preliminary results indicate hydrogel dynamics should be taken into account when designing in vivo probes and suggest that the soft material in vivo may display stiffer properties than those in vitro. We believe this work provides important insights on hydrogel-tissue interface and inherent limitations associated with the use of ultra-soft hydrogels for implantable neural interfaces.

Hydrogel based soft materials with chemical functionalities that allow controlled degradation of the polymer are utilized as active stimuli responsive platforms for numerous applications. As one example, a hydrogel with multiple degradable functional groups that degrade in response to different wavelengths of light enables sequential release of drugs from the network. Herein, we present Dissipative Particle Dynamics (DPD) based simulations of degradation in tetra-arm polyethylene glycol (tetra-PEG [1]) hydrogels. Controlled degradation can be introduced in these gels via several chemical pathways [2,3]. In our DPD model we use the modified segmental repulsive potential (mSRP [4]) to avoid unphysical polymer chain crossing and we first establish model parameters that mimic the hydrophilicity of PEG. Further, we use our recently developed framework [5] to introduce controlled degradation in these gels and measure the fraction of degradable bonds intact during degradation. Our method allows modeling of first order degradation kinetics in these gels. We track the evolution of mass loss from bulk degrading gels and note the occurrence of a slow mass loss regime due to erosion followed by a fast regime due to reverse gelation of the polymer network. We quantify the reverse gel point of these gels by tracking the size of the second largest cluster during degradation. We focus on the effect of finite size on mass loss and reverse gel point calculations and compare these effects with previously developed scaling [6]. The reverse gel point for tetra-PEG hydrogels measured from our simulations corresponds well with the value obtained from percolation theory on a diamond lattice.

References:
1. Sakai, T., Matsunaga, T., Yamamoto, Y., Ito, C., Yoshida, R., Suzuki, S., Sasaki, N., Shibayama, M., & Chung, U. I. (2008). Design and fabrication of a high-strength hydrogel with ideally homogeneous network structure from tetrahedron-like macromonomers. Macromolecules, 41(14), 5379-5384.
2. Li, X., Tsutsui, Y., Matsunaga, T., Shibayama, M., Chung, U. I., & Sakai, T. (2011). Precise control and prediction of hydrogel degradation behavior. Macromolecules, 44(9), 3567-3571.
3. Azagarsamy, M. A., McKinnon, D. D., Alge, D. L., & Anseth, K. S. (2014). Coumarin-based photodegradable hydrogel: Design, synthesis, gelation, and degradation kinetics. ACS Macro Letters, 3(6), 515-519.
4. Sirk, T. W., Slizoberg, Y. R., Brennan, J. K., Lisal, M., & Andzelm, J. W. (2012). An enhanced entangled polymer model for dissipative particle dynamics. The Journal of chemical physics, 136(13), 134903.
5. Palkar, V., Choudhury, C. K., & Kuksenok, O. (2020). Development of Dissipative Particle Dynamics framework for modeling hydrogels with degradable bonds. MRS Advances, 5(17), 927-934.
6. Lin, T. S., Wang, R., Johnson, J. A., & Olsen, B. D. (2018). Topological structure of networks formed from symmetric four-arm precursors. Macromolecules, 51(3), 1224-1231.

In living systems, there are many autonomous and oscillatory phenomena to sustain life such as heart beating. We developed “self-oscillating” polymer gels that undergo spontaneous cyclic swelling–deswelling changes without any on–off switching of external stimuli, as with heart muscle. The self-oscillating gels were designed by utilizing the Belousov-Zhabotinsky (BZ) reaction, an oscillating reaction, as a chemical model of the TCA cycle. We have systematically studied these self-oscillating polymer gels since they were first reported in 1996. Potential applications of the self-oscillating polymers and gels include several kinds of functional material systems such as biomimetic actuators, mass transport systems and functional fluids. For example, it was demonstrated that an object was autonomously transported in the tubular self-oscillating gel by the peristaltic pumping motion similar to an intestine. Further, self-oscillating polymer brush surface like cilia, vesicles or colloidosomes undergoing cell-like autonomous shape oscillations with buckling, was prepared. Besides, autonomous sol-gel oscillation and amoeba-like motion was realized utilizing well-designed block copolymer solution. In this presentation, our recent progress on the self-oscillating polymer gels is summarized.

Robots today rely on rigid components and electric motors based on metal and magnets, making them heavy, unsafe near humans, expensive and ill-suited for unpredictable environments. Nature, in contrast, makes extensive use of soft materials and has produced organisms that drastically outperform robots in terms of agility, dexterity, and adaptability. To create a new generation of soft, life-like robots that reproduce the vast capabilities of biological systems, we need to develop actuators that replicate the astonishing all-around actuation performance of biological muscle. Hydraulically Amplified Self-healing ELectrostatic (HASEL) transducers are a new class of self-sensing, high-performance muscle-mimetic actuators, which are electrically driven and harness a mechanism that couples electrostatic and hydraulic forces to achieve a wide variety of actuation modes. Current designs of HASEL artificial muscles exceed actuation stress of 0.3 MPa, linear strain of 100%, specific power of 600W/kg, efficiency of 30% and bandwidth of 100Hz; all these metrics match or exceed the capabilities of biological muscle. This talk gives an overview over the latest developments, including materials systems, modeling, new designs of actuators, fabrication techniques, and creation of untethered soft robotic devices.

Materials that perform complex chemical signal processing are ubiquitous in living systems. Their synthetic analogs would transform developments in biomedicine, catalysis, and many other areas. By drawing inspiration from biological signaling dynamics, we show how simple hydrogels have a previously untapped capacity for non-equilibrium chemical signal processing and integration. Using a common polyacrylic acid hydrogel, with divalent cations and acid as representative stimuli, we demonstrate the emergence of non-monotonic osmosis-driven spikes and waves of expansion/contraction, as well as traveling color waves. These distinct responses emerge from different combinations of rates and sequences of arriving stimuli. A non-equilibrium continuum theory we developed quantitatively captures the nonmonotonic osmosis-driven deformation waves and determines the onset of their emergence in terms of the input parameters. These results suggest that simple hydrogels, already built into numerous systems, have a much larger sensing space than currently employed.

Nature is masterful at using limited components and basic driving forces to achieve complex tasks, such as high power movement and multi-structure assembly, across a broad range of size scales. The materials that enable these achievements often rely upon the integration of phases that allow for internal transport, elastic energy storage, system protecting dissipation, and tunable sensitivity to interfacial interactions. Accordingly, polymer gels, which combine liquid phases with shear-sustaining macromolecular network structures, offer a robust materials platform for transferring lessons from nature into synthetic engineered devices. Here, we describe two examples from our research group of how to take advantage of mesoscale structural asymmetry, mechanics, liquid transport, and interfacial interactions to achieve new engineered capabilities. The first example takes inspiration from multiple examples in nature, including mantis shrimp and trap-jaw ants, that use Latch-Mediated Spring Actuation (LaMSA) to achieve high power, impulsive movements. We demonstrate how transient metastable deformations associated with swelling and deswelling of a polymer gel can be exploited to generate mechanical bi-stability, giving rise to multiple, self-repeating, snap-through movements. We introduce models to quantitatively describe these mechanisms and harness them to develop autonomous jumping devices. In a related manner, the second example describes the use of structural asymmetry to mediate swelling/deswelling processes and elastic restoring forces to control the motion and assembly of mesoscale polymer gel ribbons. Collectively, both examples provide new insight into how polymer gel properties, related to elasticity, diffusion, and interfacial forces, can combine with purposeful structural design to yield complex tasks, which can be used in the development of microscale robots and new adaptable composite materials.

Recent research efforts have focused on developing soft, flexible, compliant materials for robotics, biointerfacing, and biosensing applications. Because of their intrinsic softness, these materials are susceptible to cut, puncture, scratch, and/or tear damage that compromise their physical integrity, and therefore self-healing properties are indispensable for soft machines and devices operating in dynamic environments. However, current self-healing materials have shortcomings that limit their practical application, such as low healing strength (below MPa) and long healing times (hours).
Here, we introduce high-strength bioinspired synthetic proteins that self-heal micro- and macro-scale mechanical damage within a second by local heating. These protein hydrogels are systematically optimized to improve their hydrogen-bonded nanostructure and network morphology, with programmable healing properties (23 MPa strength after 1 second of healing) surpassing those found in other natural and synthetic soft materials by several orders of magnitude. Such healing performance opens new opportunities for bioinspired materials design, and addresses current limitations in self-healing materials for soft robotics and wearable technology.

The interest in artificial muscles has been expanding due to the shortcomings of traditional motors and actuators, such as piezoelectric actuators and shape memory alloys. Stiffness incompatibility with human bodies and IR-detectable actuation mechanisms are among the limitations of the traditional actuators. Soft matter and polymers, including hydrogels, as artificial muscles offer great potential to enhance robotic applications where lightweight and flexible structures are desired. Upon application of an external stimulus, polymer artificial muscles can expand or contract, similar to a mammalian muscle, replicating comparable stroke and stiffness, which enables safe interactions with humans. pH is one of the stimuli which provides a silent and athermal motion to artificial muscles. pH-driven polymer gels can lead to significant swelling and deswelling behaviors when exposed to acid and basic environments and provide muscle-like actuation when in a fiber form. In this work, we investigated the actuation behaviors of polyacrylonitrile (PAN) gel fibers by exploiting structural adjustments in which a simple but efficient method, twisting and coiling approach was applied. In this manner, the material response –dimensional change with change in pH- was enhanced with the peculiar structural design of a coil, leading to drastically augmented strokes. Here, we first characterized electrospun PAN nanofibers and commercially available PAN microfibers in terms of fabrication conditions. In this step, the variables of thermal stabilization and hydrolysis, resulting in a PAN pH-responsive gel, were tested in order to obtain optimum actuation conditions. Aligned micro and electrospun nanofibers prepared with different fabrication conditions were actuated at various levels of mechanical loading. A maximum of ~54% actuation was achieved under no stress and it was found that higher thermal stabilization results in lower actuation. Radius and overall volume change of pH-responsive single PAN microfiber were measured. Next, as-received PAN microfibers were highly twisted and coiled to produce volume-change induced actuation. Coiled PAN fibers yielded a promising actuation performance compared to their linear and aligned counterparts. Analytical models relating material response to structural responses were studied. This work shows that pH-responsive PAN gel fibers can be further enhanced in terms of actuation performance through structural design.

Recently, new tissue engineering approaches are being developed as an alternative to traditional treatments for articular cartilage (AC) repair. Being an avascular tissue, AC has a limited ability to heal from defects caused by traumas and/or degenerative diseases. Materials in the form of hydrogels are particularly attractive as owing to their biocompatibility, degradability, and ability to homogeneously mix with cells and smart nanomaterials. Hydrogels can be injectable, thus to easily fill defects with different shapes, thus repairing the articular cartilage in a minimally invasive way.
Several tissue engineering approaches have been proposed to restore the AC native properties [1]. This specialized tissue provides a low-friction surface for articulation, guaranteeing shock-absorption and wear-resistance [2]. Despite the noticeable efforts spent in the recent years, there is still a high difficulty to reproduce in vitro the mechanical and lubrication properties of AC.
We developed a bilayered hydrogel made of blends of Gellan Gum (GG) and Polyethylene glycol diacrylate (PEGDA), able to mimic the mechanical and lubrication features of AC. Graphene Oxide (GO) was used as an effective lubricant agent [3]. GG (1.5 % wt. in deionized water) was mixed with PEGDA (Mn: 575) at different concentration (10 and 15 % wt. for top and bottom layer, respectively). The photocrosslinking was enabled by the addition of Irgacure 2959 (0.1 % wt.) and different UV light exposure time (5 and 10 min) have been tested. Then, samples were immersed in magnesium chloride (MgCl₂, 1 % wt. in deionized water) for 10 min and/or culture medium (DMEM) for 24 h to enable the ionic crosslinking. Mechanical compression tests allowed to determine the optimal crosslinking parameters. We found two combination of crosslinking able to match the compression Young's modulus of the human AC, which ranges from 0.28 ± 0.16 MPa to 0.73 ± 0.26 MPa, respectively for its superficial and deep layer [4]. We achieved the targeted range of Young’s modulus values for the top (0.18 ± 0.06 MPa) and bottom (0.80 ± 0.15 MPa) layers of AC by combining photo (5 min) and ionic crosslinking with MgCl₂. The contribution of ionic crosslinking with MgCl₂ was also more effective than the UV exposure time for the improvement of the toughness and fracture stress/strain of the hydrogels, important features of AC. GO nanosheets were synthesized as described in [5] and added to the top layer solution (0.01 % wt.). The hydrogels with and without GO were analyzed with a custom setup (flat-on-flat geometry) made of using a MCR 102 rheometer equipped with the Tribocell T-PTD200 and a Peltier temperature control. Tribological analyses demonstrated that the non-doped formulation possessed a smaller friction factor (~0.03) in the static regime than the doped formulation (~0.04), while the presence of GO led the friction factor to smaller values in the kinetic regime, as opposed to the bare hydrogel in which that value progressively increased.
In summary, we demonstrated the achievement of the target compressive Young’s modulus of AC layers and the improved lubricant behavior provided by the presence of GO in the kinetic regime of compression, which is important for guaranteeing low friction in the articulation during daily life activities. These results are extremely promising in view of the fabrication of a multi-layered synthetic implant for restoring AC defects.
ACKNOWLEDGMENTS
This work received funding from the European Union's Horizon 2020 research and innovation program, grant agreement No 814413, project ADMAIORA.
REFERENCES
[1] J. W. Reboredo et al. Adv. Healthc. Mater, 5, 2191, 2016.
[2] A. J. Sophia Fox et al. Sports Health, 1: 461, 2009.
[3] Y. Meng et al. J. Phys. Chem. A, 122: 3157, 2018.
[4] R. Krishnan et al. J. Biomech. Eng., 125: 569, 2003.
[5] O. Marciano et al. Langmuir, 32: 11672, 2016.

Electron/X-ray focused beams fabrication of hydrogels with submicron resolution and rate inside liquid precursor solutions would be highly demanded development which, however, is hard to realize due to the vacuum incompatibility of liquid samples. In this contribution, we resolve this impediment and demonstrate a technique for in-liquid focused beam induced crosslinking of hydrogels using fluidic enclosures equipped with electron/x-ray transparent windows. Being inspired by continuous liquid interface production 3D printing technology (CLIP)[1], we developed an alternative method of controllable delamination of the e-beam printed layer from the supporting membrane. Our approach is based on electrochemical quenching of the crosslinking process at the electrified membrane-solution interface. The potential of this technique for sensorics, bioelectronics, interfacing, and drug delivery is demonstrated via in situ addressable immobilization of live-cell, synthesis of nanocomposite hydrogels, and microfabrication of photonic sensors[2].

[1] J. R. Tumbleston et al., "Continuous liquid interface production of 3D objects," Science, vol. 347, no. 6228, pp. 1349-1352, 2015.
[2] T. Gupta et al., "Focused Electron and X-ray Beam Crosslinking in Liquids for Nanoscale Hydrogels 3D Printing and Encapsulation," arXiv preprint arXiv:1904.01652, 2019.

Light technologies have enabled numerous biomedical devices to assess health and treat disease, among which optical fibers permit light transmission between the external world and human nervous system. The peripheral nervous system flexes with the human body during movement, while silica-based optical fibers with limited deformability constrain the natural movement of the nerves, impeding light delivery in freely moving animals. On the other side, the high compliance, high water content, and biocompatibility make hydrogels an ideal material candidate for optic devices, especially for those in close contact with biological organisms. However, existing hydrogel optical fibers suffer from low mechanical stability, poor coupling with external optics, and severe light leakage. Here, we present a fatigue-resistant hydrogel-based optically stimulating technology (FAR-HOST) that utilizes nanocrystalline hydrogels as optical fibers for optogenetic control in the peripheral nervous system. The hydrogel optical fibers are soft and stretchable to conform to the flexible substrates, and meanwhile the formation of polymeric nanocrystals in hydrogels confers fatigue-resistance to these hydrogel materials against repeated movements. In addition, hydrogels with polymeric nanocrystals exhibit a relatively high refractive index that minimizes interfacial light leakage, and high transparency that reduces light absorption or scattering, synergistically contributing to efficient light transmission. In vitro and in vivo results demonstrate that using FAR-HOST to exert optogenetic control over the sciatic nerve, revealing its potentials diagnostic imaging, health monitoring, and neuromodulation.

Immobilization of biosensors in or on a functional material is critical for subsequent device development and translation to wearable technology. Here we present the development and assessment of an immobilized quantum dot - transcription factor - nucleic acid complex for progesterone detection as a first step toward such device integration. The sensor is composed of a polyhistidine-tagged transcription factor linked to a quantum dot and a fluorophore-modified cognate DNA, and embedded within a hydrogel as an immobilization matrix. The hydrogel is optically transparent, soft, and flexible as well as traps the quantum dot - transcription factor DNA assembly but allows free passage of the analyte, progesterone. Upon progesterone exposure, DNA dissociates from the quantum dot - transcription factor DNA assembly resulting in an attenuated ratiometric fluorescent output via Förster resonance energy transfer. The sensor performs in a dose-dependent manner with a limit of detection of 55 nM. Repeat analyte measurements are also similarly successful. Our approach combines a systematically characterized hydrogel as an immobilization matrix and a transcription factor – DNA binding as a recognition/ transduction element, offering a promising framework for future biosensor devices based upon allosteric transcription factor.

The main challenges in conventional color printing involve protecting ink from fading and enabling it to be rewritable. As for color displays, a liquid crystal display, for example, suffers from high power consumption and small viewing angle. Alternatively, as seen in stained glass and peacock feathers, some of the historical artifacts and natural livings exhibit rich colors, whose principle include localized surface plasmon resonance (LSPR) and/or interference effects. Recently novel color printing and displays based on these effects have been widely demonstrated.
Towards plasmonic color display at video frame rate, dynamic modulation of plasmonic coloration by using volume phase transition of responsive polymer gels has been proposed [1,2]. In these studies, a hydrogel with drastic volume responsibility to an external field was employed for fine tuning of gap distance of neighboring metal nanostructures to control of LSPR. The color modulation range, however, is still unsatisfied and far behind from practical use.
In this study, we propose a new method to widen the wavelength range of plasmonic coloration by exploiting interference between illuminating white light and LSPR scattering light. The sample consists of gold nanoparticles (AuNP; Φ ＝ 80 nm) dispersed in Poly(N-isopropylacrylamide) (PNIPAM) hydrogel, which was sandwiched between two coverslips (Fig. 1 inset). Under bright-field microscope observation, back-scattered light from AuNP interferes with white light reflected back from the bottom coverslip. Depending on the distance between AuNP and the bottom coverslip, the relative phase of interfering lights differs for individual AuNPs and they appear in different colors in a wide-range (Fig. 1). In addition, we can control the AuNP-coverslip distance via volume phase transition of PNIPAM induced by temperature control (Fig. 2 inset). Figure 2 demonstrates continuous color tuning of a single AuNP, broadly covering the chromatic diagram, upon heating and cooling of PNIPAM.

There is a significant interest in measuring biopotential signals (such as ECG and EOG) unobtrusively via novel textile-based electronics. Herein, electrodes are the interface who receives the charges in the ionic form from the body and injects them as electrons through wires. A fundamental challenge to be addressed to reliably measure biopotential parameters with fabric-based electrodes is whether we can design an electrode that has the signal quality of traditional wet electrodes and the comfort of dry electrodes. The crucial role of a hydrogel in an electrode, specifically in reducing the motion artifact, is undeniable. However, fabricating a hydrogel which can be stably grafted to the underneath plate and, more importantly, can be fully recovered after being dried out is still a great challenge among scientists. In this study, we developed a mechanically stable hydrogel as the electrolyte on our bioelectrode by taking advantage of initiated Chemical Vapor Deposition (iCVD). Our first-of-its-kind hydrogel electrodes successfully address all known drawbacks of conventional “wet” electrodes, in addition to affording high signal to noise ratio during long-term data acquisition, displaying wash-stability, breathability, no skin irritation, and being capable of further miniaturization for embedding into any wearable platforms. The functionality of these electrodes has been successfully approved by being incorporated into an eye-mask to detect eye movement (EOG). To capture additional physiological measures that are complementary to eye movement information captured by the electrodes, we embedded a fabric-based pressure sensor for pulse detection along the strap of the eyewear which let the wearer’s pulse to be imperceptibly measured, simultaneously with any eye movement. We anticipate that the ability to track pulse along with eye movement in a single device will enable a host of cutting-edge biomedical, psychological and psycho-social studies, in addition to improving the accuracy and usability of gaming and virtual reality headsets.

Circulating Tumor Cells (CTCs) are responsible for inducing metastasis when they exit from a primary tumor, they travel through blood and invade another healthy tissue. They are considered as crucial biomarkers of the prognosis of cancer patients, but they are normally found in low concentrations in the first stages of the disease and their detection and is still a challenge. Therefore, the development of biosensors capable of not only detecting, but also collecting pure CTCs is of great interest for the scientific community and society in general. Stimuli responsive materials are gaining interest for cell capture and release, specifically, poly(N-isopropylacrylamide) (pNIPAAm), which changes its configuration in response to variations in temperature above and below 32 °C in a range able to preserve cell viability. In parallel, the extensive use of conducting polymers (CPs) in the bioengineering field is enabling important advances in cell applications. This is thanks to their properties such as optical transparency, amenability to surface functionalization, high biocompatibility and chemical stability, high conductivity/weight ratio, high porosity and very good electrical and physical properties. The additional ability of CPs to be turned into mechanically soft hydrogels opened exciting new possibilities to integrate electrically conducting materials within thermoresponsive polymers and create biosensors. Here, we report a hybrid functional, conductive and thermoresponsive copolymer, based on poly(3,4-ethylenedioxythiophene) / poly(styrene sulfonate) (PEDOT:PSS) blended with pNIPAAm. The material is capable of performing label free, non-invasive cell capture, release, and simultaneous electrical monitoring of the process of cell capture and release. This technology opens a new possibility for detecting and collecting CTC biomarkers in early stage cancers for further analysis to improve patient prognosis.

Rewiring Bacterial Electron Transfer for Computational Living Materials
Austin J. Graham^1,2, Christopher M. Dundas¹, Gina Partipilo¹, Thomas M. FitzSimons^1,2, Adrianne M. Rosales^1,2, Benjamin K. Keitz^1,2
1McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, TX
²Center for the Dynamics and Control of Materials, University of Texas at Austin, Austin, TX

Keywords: living materials, synthetic biology, genetic logic

Qualities exhibited by living systems, including self-regulation, self-healing, morphology control, and environmental responsiveness, are highly attractive from a material design perspective. Collectively, these capabilities all arise from the ability of living systems to perform computation. However, traditional biological materials, such as biofilms and tissues, are generally less robust and more difficult to engineer than synthetic materials. Next-generation materials must bridge the computational abilities of natural systems with the precision of synthetic systems. These designs will require programming of genetic and transcriptional responses whose outputs can control non-biological material properties. Towards these goals, living materials are a class of materials defined by their incorporation of autonomous cells that use biological functions to control material properties. Our group recently demonstrated that leveraging extracellular electron transfer (EET) from the organism Shewanella oneidensis enables control over the redox equilibrium of metal catalysts to polymerize and cross-link syntheic materials via atom-transfer radical polymerization^1,2. Using this method, we report the production of hydrogel living materials in which S. oneidensis controls the cross-linking of methacrylated hyaluronic acid³. Cross-linking by genetic knockouts demonstrated that hydrogel formation was closely coupled to the expression of specific EET proteins, as gelation kinetics and stiffness correlated to the number of removed EET genes. Furthermore, strains complemented with an inducible EET gene showed inducer-dependent cross-linking activity and hydrogel mechanics, including both gel microstructure and bulk properties. Modeling gene expression using an activating Hill Function yielded quantitative prediction of hydrogel storage modulus, demonstrating control over material properties using design principles from synthetic biology. Genetic circuits controlling different EET genes also yielded networks with tunable properties depending on the choice of gene, demonstrating traditional buffer gate logic. By coupling EET activity to cross-link density, we have engineered a platform that utilizes autonomous bacterial metabolism to design computational materials that cross-link in response to environmental cues using genetic logic. Next, we will further demonstrate the general applicability of EET-controlled catalysis for computational material synthesis, cross-linking fully synthetic polymer networks using thiol-ene and CuAAC click chemistries. Genetic control over these chemistries will significantly expand the synthetic capability of microorganisms. Finally, more sophisticated Boolean logic, such as NOT, AND, and OR gates will enable more advanced living material computation for applications in biosensing, tissue engineering, and additive manufacturing.

1. G. Fan*, C.M. Dundas, A.J. Graham, N.A. Lynd, B.K. Keitz. “Shewanella oneidensis as a living electrode for controlled radical polymerization.” Proc. Natl. Acad. Sci. U.S.A. 115(18): 4559–4564 (2018).
2. G. Fan, A.J. Graham, J. Kolli, N.A. Lynd, B.K. Keitz. “Aerobic Radical Polymerization Mediated by Microbial Metabolism.” Nat. Chem. (in press, 2020). DOI: 10.1038/s41557-020-0460-1.
3. A.J. Graham, C.M. Dundas, A. Hillsley, D.K. Kasprak, A.M. Rosales, B.K. Keitz. “Genetic Control of Radical Cross-linking in a Semisynthetic Hydrogel.” ACS Biomater. Sci. Eng. 6(3): 1375–1386 (2020).

Water scarcity has been an increasingly severe threat to our society. Solar vapor generation provides a sustainable means for desalination and water purification technologies. With highly tunable structures, unique polymer-water interactions, and ease of integration with functional materials, hydrogels show great potential for efficient solar water purification. The rational design and engineering of hydrogel surfaces have a substantial impact on the interfacial solar water vaporization process. Here, we will discuss effective ways to tailor the surface topography and wetting states of hydrogel solar evaporators to accelerate the solar vapor generation rate. Specifically, the nanotextured topography of the surface can be fabricated by a liquid-liquid interface-guided gelation process, resulting in an increased heat flux at the sharply dimpled hydrogel-air interface. In addition, hydrogel evaporators with inhomogeneous surface wettability demonstrate an ultrahigh evaporation rate with synergistic contributions from both wetting regions. Molecular dynamics simulation reveals the surface-modulated escaping behavior of water molecules. By applying hydrophilic polymers as building blocks, the hydrogel evaporators have been endowed with multifunctionalities, such as antifouling and complex contaminants removal, to improve both quantity and quality of collected water. Together with an easy-to-employ and portable purification prototype, hydrogels are an emerging materials platform for high-performance yet cost-effective water purification applications.

Genetically modified microorganisms (GMMs) can enable a wide range of important applications, including environmental sensing, precision therapeutics, and responsive materials. However, the containment of GMMs to prevent environmental escape and satisfy regulatory requirements is a bottleneck for real-world use. While biochemical strategies have been developed to restrict unwanted growth and replication of GMMs in the environment, there is a need for deployable physical containment technologies to achieve redundant, multi-layered, and robust containment. In addition, form factors that enable easy retrieval would be useful for environmental sensing. To address this challenge, we developed a hydrogel-based encapsulation system for GMMs that incorporates a biocompatible multilayer tough shell and an alginate-based core. This DEployable Physical COntainment Strategy (DEPCOS) allows no detectable GMM escape, bacteria to be protected against environmental insults including antibiotics and low pH, controllable lifespan, and easy retrieval of genetically recoded bacteria. To highlight the versatility of a DEPCOS, we demonstrate that robustly encapsulated cells can execute useful functions, including performing cell-cell communication with other encapsulated bacteria and sensing heavy metals in water samples from the Charles River. We envision that our multilayered physical and chemical containment strategy will facilitate the realization of a wide range of real-world applications for ‘living’ biosensors.

Superabsorbent polymer gels that can absorb a significant amount of water are widely used in materials such as diapers and for keeping soil moist. These gels are typically in the form of microscale beads. The same gels can also be made as macroscopic solids (e.g., a sheet or cube), but these solids take a long time (~ 24 h) to swell in water. For a large, solid gel to swell rapidly, it is necessary to make it porous, but porous gels tend to be fragile.

Here, we present a simple and low-cost approach to create solid gels that are both porous and highly robust. Our approach involves the polymerization of a foamed monomer solution, with the bubbles of the foam being stabilized by novel polymers. The final dried material is typically in the form of a sheet (thickness ~ 1 mm, length and width from 1 to 100 cm). The sheet is flexible and robust; it can be rolled up like a paper towel and cut into patches of desired size. When added to water, the gel-sheet absorbs 150 times its weight in water within 30 s, and the swollen sheet can be lifted up by hand.

We expect this type of superabsorbent material to have many applications, one of which is in stopping bleeding from severe wounds. In that regard, our gel-sheet is able to rapidly absorb whole blood – up to 60 times its weight within a minute. Moreover, due to the presence of the polymer stabilizers, the blood tends to remain immobilized in the swollen gel. Data from experiments with bleeding models in animals will be presented.

The deployment of soft robotic technologies for rescue and navigation missions are expected to provide safe object-machine interactions and substantially reduce the risks associated with operation staff. Yet, most of the reported soft robots were made of soft matter with insufficient material stability to support normal robotic operations in extreme environments. Installation of conventional protective modules/exoskeletons onto soft robots inevitably compromises their compliant/complex actuations and increases their energy consumption rates. Herein, we developed a set of soft robotic skins composed of two-dimensional materials (2DM) and gelatin hydrogels, featuring with skin-like multifunctionality (including stretchability, thermoregulation, threat protection, strain sensation). The 2DM-integrated hydrogel skins (2DM/H) enabled the protected soft robots to execute designated missions upon exposure to various environmental threats. All 2DM/H robotic skins demonstrated autonomic perspiration behaviors and maintained mild machine temperatures under high heat. By adopting different 2DM units (including graphene oxide (GO), montmorillonite (MMT), titanium carbide (MXene)), the 2DM/H-protected grippers performed soft grasping missions in organic liquids (GO/H), open fire (MMT/H), electromagnetic radiation and biocontamination (MXene/H). Furthermore, through blending MXene into the hydrogel layer, the MXene-blended hydrogel skin (M-H) was strain sensitive and capable of providing piezoresistive signals in real-time. We next applied conformal GO/M-H skin onto a soft gripper, which demonstrated the ultimate integration of skin-mimicking capabilities to handle irregular objects in hot organic liquids. Two demonstrations were finally presented: a dual-bellows walker robot with MMT/H skin performed a vision-guided search mission in an open fire, and a GO/H-protected batoid robot conducted autonomous underwater locomotion/navigation upon serious DCM spills.

Many applications of hydrogels rely on their ability to deliver encapsulated solutes such as drugs or dyes to an external medium. However, a problem in many such applications is that, the moment the gel is placed in contact with water, the solutes rapidly leak out by diffusion. Ideally, there should be a way to regulate the release of solutes – i.e., to ensure zero release until a desired time, and thereafter, for the release to be ‘switched on’. Moreover, it would be even better if this was a repeatable switch, i.e., if the gel could be cycled many times between the on and off states. Such a perfect, cyclical on-off release of contents from hydrogels has never been achieved to our knowledge.

We address this challenge by taking inspiration from structures found in nature such as fruits and vegetables, which have a hydrophobic skin that envelops and protects their water-rich core. We have found a way to synthesize a soft hydrophobic skin around any gel. The initial skin completely prevents hydrophilic solutes from leaking out of the gel into the external solution. The skin is also equipped with redox-responsive properties. That is, in the presence of oxidants, the skin becomes hydrophilic, thereby ‘turning on’ the release of solutes out of the gel. Conversely, solute release can be ‘turned off’ at any time by adding a reducing agent that reverts the skin to its hydrophobic state. Thus, our smart skin enables regulated (on-off) release of solutes out of a gel, and this concept is likely to be useful in many applications.

Over the last decade, three-dimensional bioprinting has offered great versatility to fabricate biomimetic volumetric tissues that are both structurally and functionally relevant to their native counterparts. The technology enables precise control over the composition, spatial distribution, and architecture of the bioprinted constructs, facilitating recapitulation of the delicate shapes and structures of targeted organs and tissues. This talk will discuss our recent efforts on developing various cytocompatible and cell-instructive bioink formulations, as well as their processing methods, for the fabrication of engineered tissues towards regenerative medicine and tissue model engineering applications, using a series of established or customized bioprinting strategies.

In mussels, the adhesive proteins that are instrumental for attachment to wet surfaces are known to contain high levels of 3,4-dihydroxy-L-alanine (DOPA), often located adjacent to amino residues such as lysine (Lys). The special synergistic relationship between catechols and amines is a subject of high interest, not only for understanding native proteins but also for informing the design of bioinspired polymer systems. Other research groups have shown that catechol and amine functional groups act synergistically to enhance adhesion at wet surfaces, however reports of catechol-amine interfacial phenomena on a single molecule level have been limited. In this talk we will describe single molecule force spectroscopy (SMFS) measurements that are providing new insights into interactions between Lys-DOPA peptides and various surfaces. Of particular interest is the impact of chemical composition (DOPA and Lys), peptide length and topology (i.e. distribution of adhesive elements along a polymer) on interfacial adhesion to a wet substrate. The results may inform the future design of novel polymer adhesives, including adhesive hydrogels, pressure sensitive adhesives and high-strength thermoset adhesives.

Marine mussels secrete adhesive proteins that enable these organism to anchor themselves to various substrate (i.e., ship hull, rock) in a rough, intertidal zone. These mussel foot proteins contain a unique amino acid, L-3, 4 dihydroxyphenylalanine (DOPA), that is responsible for strong interfacial binding and curing of the proteins. The catechol side chain of DOPA is capable of participating in various stimuli responsive, reversible interactions, dictated by its oxidation state. In this presentation, I will describe our efforts in utilizing these interactions in designing various types of smart biomaterial. We have incorporated catechol-metal ion coordination bond to design hydrogel actuators that can fold into various 3-dimentional shapes. We have also utilized catechol-boronic acid complexation chemistry to design moisture-resistant smart adhesive with tunable adhesive properties. Most recently, we demonstrated the feasibility of using applied electricity to directly deactivate catechol-based adhesive that is bonded to a surface.

In living systems, there are many autonomous and oscillatory phenomena to sustain life such as heart beating. We developed “self-oscillating” polymer gels that undergo spontaneous cyclic swelling–deswelling changes without any on–off switching of external stimuli, as with heart muscle. The self-oscillating gels were designed by utilizing the Belousov-Zhabotinsky (BZ) reaction, an oscillating reaction, as a chemical model of the TCA cycle. We have systematically studied these self-oscillating polymer gels since they were first reported in 1996. Potential applications of the self-oscillating polymers and gels include several kinds of functional material systems such as biomimetic actuators, mass transport systems and functional fluids. For example, it was demonstrated that an object was autonomously transported in the tubular self-oscillating gel by the peristaltic pumping motion similar to an intestine. Further, self-oscillating polymer brush surface like cilia, vesicles or colloidosomes undergoing cell-like autonomous shape oscillations with buckling, was prepared. Besides, autonomous sol-gel oscillation and amoeba-like motion was realized utilizing well-designed block copolymer solution. In this presentation, our recent progress on the self-oscillating polymer gels is summarized.

Robots today rely on rigid components and electric motors based on metal and magnets, making them heavy, unsafe near humans, expensive and ill-suited for unpredictable environments. Nature, in contrast, makes extensive use of soft materials and has produced organisms that drastically outperform robots in terms of agility, dexterity, and adaptability. To create a new generation of soft, life-like robots that reproduce the vast capabilities of biological systems, we need to develop actuators that replicate the astonishing all-around actuation performance of biological muscle. Hydraulically Amplified Self-healing ELectrostatic (HASEL) transducers are a new class of self-sensing, high-performance muscle-mimetic actuators, which are electrically driven and harness a mechanism that couples electrostatic and hydraulic forces to achieve a wide variety of actuation modes. Current designs of HASEL artificial muscles exceed actuation stress of 0.3 MPa, linear strain of 100%, specific power of 600W/kg, efficiency of 30% and bandwidth of 100Hz; all these metrics match or exceed the capabilities of biological muscle. This talk gives an overview over the latest developments, including materials systems, modeling, new designs of actuators, fabrication techniques, and creation of untethered soft robotic devices.

Materials that perform complex chemical signal processing are ubiquitous in living systems. Their synthetic analogs would transform developments in biomedicine, catalysis, and many other areas. By drawing inspiration from biological signaling dynamics, we show how simple hydrogels have a previously untapped capacity for non-equilibrium chemical signal processing and integration. Using a common polyacrylic acid hydrogel, with divalent cations and acid as representative stimuli, we demonstrate the emergence of non-monotonic osmosis-driven spikes and waves of expansion/contraction, as well as traveling color waves. These distinct responses emerge from different combinations of rates and sequences of arriving stimuli. A non-equilibrium continuum theory we developed quantitatively captures the nonmonotonic osmosis-driven deformation waves and determines the onset of their emergence in terms of the input parameters. These results suggest that simple hydrogels, already built into numerous systems, have a much larger sensing space than currently employed.

Hydrogels are among the first biomaterials expressly designed for their use in biomedicine. However, state-of-the-art applications of hydrogels are severely limited because of their mechanical properties. Most hydrogels are either too soft or too brittle to be used for load-bearing applications. To overcome this shortcoming, double network (DN) hydrogels composed of two interpenetrating polymeric networks have been introduced. These DN hydrogels are composed of a highly crosslinked network, the filler, responsible for the stiffness of the hydrogel and a second loosely crosslinked one, the matrix, that regulates the toughness of the material. Despite this great improvement in mechanics, composition and structural complexity found in soft natural tissues remain yet to be matched. Indeed, soft natural materials possess locally varying compositions and structures that are well-defined over many length scales. By contrast, synthetic hydrogels typically have an ill-defined microstructure and their composition is most often homogeneous. To obtain a better structural control, we introduce a novel 3D printing approach to fabricate strong and tough soft materials, namely double network granular hydrogels (DNGHs). This is achieved with an ink composed of microgels that are swollen in a monomer-containing solution. Upon printing and post-curing, the monomers are converted into a percolating network, yielding a solid DNGH. These DNGHs possess mechanical properties that are superior to reported additive manufactured hydrogels. In this work, we demonstrate that this technique enables printing macroscopic strong and tough objects with a high shape fidelity. Because this new technology employs a microgel-based ink, it significantly extends the choice of materials that can be additive manufactured. Moreover, the modularity of the jamming approach allows for the combination of different ink in the same printing process, resulting in mechanically robust stimuli responsive structures.

Over the last few decades, living cells have been employed as factories to make organic molecules, polymers, drugs, and fuels. Lately, living cells are being engineered to make materials and/or to modulate its properties, giving rise to an exciting field of Living Materials. Earlier work has shown that engineered living materials (ELMs) can bind to nanoparticles, catalyze reactions, and modulate conductivity amongst others.

Herein, we present a versatile strategy for the fabrication of living hydrogels directly from the bacterial culture by a simple filtration protocol. This hydrogel comprises of E. coli embedded in an extracellular matrix of engineered protein fibers. Genetic programming enables the hydrogels to be customized to interact and adhere to different tissues of the gastrointestinal tract. The designed mucoadhesive and anti-inflammatory hydrogels can be sprayed directly in the gut serving as an innovative wound healing strategy for the gut lumen.

By genetic engineering, we have also developed a functional microbial ink for 3D printing of living materials. This microbial ink is produced from engineered bacteria and can also be embedded with desired microbes to enable the printing of complex 3D architectures having various functions like sensing and sequestration.

Thus, we demonstrate the very first examples of microbial ink for 3D printing and the biomedical application of living materials. This unique platform of genetically programmable living hydrogels provides unprecedented opportunities to harvest the characteristics of living systems and thereby enables advanced applications of living materials.

Reliable functions of bioelectronic devices require conformal, stable, and conductive interfaces with biological tissues. Integrating bioelectronic devices with native tissues usually relies on physical attachment or surgical suturing. Whilst these conventional methods face challenges such as non-conformal contact, unstable fixation, tissue damage and/or scar formation. Here we present a new class of bioadhesive electronic devices capable of compatibly and robustly integrating with various wet dynamic tissues, offering a promising solution beyond suturing and physical attachment to address the aforementioned challenges. The bioadhesive electronics are enabled by a new nanocomposite interface that can provide rapid (adhesion formation within five seconds), robust (interfacial toughness over 400 J m^-2), and on-demand detachable adhesion of bioelectronic devices on diverse wet tissues. The nanocomposite interface is electrically conductive (conductivity over 2.6 S m^-1) to allow bi-directional bioelectronic communications. We demonstrate applicability, mechanical and electrical stability, biocompatibility, and bioelectronic recording and stimulation functionalities of the bioadhesive electronics based on ex vivo porcine and in vivo rat models. This study provides a new powerful platform for diverse bioelectronics to address the long-standing challenges in human-machine interface.

Dynamic covalent chemistry has emerged as an elegant molecular design strategy to engineer functional polymer networks that combine advantageous properties of both chemically and physically cross-linked materials. Dynamic covalent networks (DCvNs) are increasingly used in advanced materials design with applications ranging from recyclable thermosets to self-healing hydrogels. However, the relationship between the underlying chemistry at the junctions of DCvNs and their macroscopic properties is still not fully understood. In this presentation, we will outline a robust framework to predict how complex network behavior in DCvNs emerges from the chemical landscape of the dynamic chemistry at the junction. We use ideal dynamic covalent boronic ester-based hydrogels as model DCvNs. We will describe physical models that explain how viscoelastic properties, as measured by shear rheometry, are linked to the molecular behavior of the dynamic junction, quantified via fluorescence and NMR spectroscopy and DFT calculations. Additionally, shear rheometry is combined with Eyring Transition State Theory to quantify the kinetics and thermodynamics of network rearrangements, enabling a mechanistic understanding including preferred reaction pathways for dynamic covalent chemistries. We apply this approach to corroborate the ‘loose-bolt’ postulate for the reaction mechanism in Wulff-type boronic acids. These findings, grounded in molecular principles, advance our understanding and rational design of dynamic polymer networks, improving our ability to predict, design, and leverage their unique properties for future applications. We will also discuss applications of these materials for the thermal stabilization of biologics and as tunable viscoelastic materials.

Living tissues show an extraordinary adaptiveness to strain, which is crucial for their proper biological functioning. The physical origin of this mechanical behaviour has been widely investigated using reconstituted networks of collagen fibres, the principal load-bearing component of tissues. However, collagen fibres in tissues are embedded in a soft hydrated polysaccharide matrix which generates substantial internal stresses whose effect on tissue mechanics is unknown. Here, by combining mechanical measurements and computer simulations, we show that networks composed of collagen fibres and a hyaluronan matrix exhibit synergistic mechanics characterized by an enhanced stiffness and delayed strain-stiffening. We demonstrate that the polysaccharide matrix has a dual effect on the composite response involving both internal stress and elastic reinforcement. Moreover, the matrix has a pronounced effect on fracture of the networks, leading to enhanced toughness and a transition from brittle to ductile behaviour. Our findings elucidate how tissues can tune their strain-sensitivity over a wide range and provide a novel design principle for synthetic materials with programmable mechanical properties.

[1] F.Burla, J. Tauber, S. Dussi, J. van der Gucht, G.H. Koenderink, Nature Physics, 15, 549 (2019)
[2] S. Dussi, J. Tauber, J. van der Gucht, Physical Review Letters 124 (2020), 018002
[3] F. Burla, S. Dussi, C. Martinez-Torres, J. Tauber, J. van der Gucht*, G.H. Koenderink, PNAS 117 (2020), 8326

Interest in hydrogels over the past couple of decades has exploded for a wide range of biomedical applications, including drug delivery, and tissue engineering.¹ There is a huge interest in building these supramolecular structures from non-covalent interactions, e.g. hydrogen bonds, host-guest interactions, which provide an easy tailoring of dynamic properties, impart shear-thinning and thus injectability and self-healing, making them more amenable to biomedical applications.
Our group focuses on harnessing and understanding simple gelation processes in materials that come from renewable sources or are easily accessible. We exploit hybrid gelation processes to the cross-linking process,² spontaneous self-assembly in mixtures of modified polymers and surfactants,³ formation of pseudopolyrotaxanes with cyclodextrins,⁴ and thermally-triggered gelation.⁵ In this talk I will present some of our recent work on self-assembled gels and in particular how we use small-angle neutron scattering to elucidate the spatial organisation of the networks that sustain the rheological properties, and ultimately build towards a rationale for hydrogel formulations.

[1] C. A. Dreiss (2020) Curr. Opinion Colloid Interface Sci. 48, 1; C. Salzlechner et al. (2020) Adv. Healthcare Mat. 9, 4, 1901134; da Silva & Dreiss (2016) Polym. Int. 65, 268
[2] M.A. da Silva et al. (2017) J. Pol. Sci. B. 55, 1850; M. A. da Silva (2015) Biomacromolecules 16, 1401; M. A. da Silva et al. (2015) Biomacromolecules 16, 1401.
[3] N. Zoratto et al. (2019) J. Colloid Interface Sci., 556, 301
[4] M. Serres-Gómez et al. (2018) Langmuir, 34, 10591
[5] J. Puig-Rigall et al. (2017) J. Colloid Int. Sci. 524, 42

Understanding and tailoring the self-assembly of supramolecular moieties is a challenging subject with potential implications in materials engineering and biological function. Here we discuss two problems associated with the viscoelastic properties of (i) hydrogel mixtures due to competitive interactions and (ii) organogels due to the presence of traces of humidity.
Concerning the former, we investigated a class of binary hydrogels made by mixing fibrillar supramolecular polymers that are formed from two compounds: 1,3,5-benzene-tricarboxamide decorated with aliphatic chains terminated by tetra(ethylene glycol) (BTA) and a 20 kg/mol telechelic poly(ethylene glycol) decorated with the same hydrogen bonding BTA motif on both ends (BTA-PEG-BTA). We found that the respective single-compound-based supramolecular systems form very different networks which exhibit drastically different rheology. More strikingly, mixing the compounds results in a non-monotonic dependence of modulus and viscosity on composition, suggesting a competition between interactions of the two compounds, which can then be used to fine-tune the mechanical properties.
The latter problem concerns the self-assembly of supramolecular moieties in organic solvents which is affected by the presence of trace amounts of water in the monomeric state that induce competitive association and change the helicity of the assembled structure. We investigated an organogel in dodecane (biphenyl tricarboxamide, BPTA) and found that water affects the self-assembled structure by changing the persistence length and contour length of the fiber. The content of water in the fiber changed with temperature, bequeathing the linear and nonlinear viscoelastic properties with unusual temperature responsiveness. For instance, as the temperature increased from 15 to 35^oC, the relaxation time of the system varied non-monotonically with temperature. This stems from the fact that the system loses its reversible and dynamic character for temperatures above 35^oC where water does not mediate the association of BPTA units.
These findings are discussed in the context of existing theories of living polymers and of the perspective of designing gels with desired and tunable properties.

Work in collaboration with E. Vereroudakis (Crete), N.J. Van Zee (ESPCI, Paris), E. Del Gado (Georgetown) and E.W. Meijer (T. U. Eindhoven).

Nature is masterful at using limited components and basic driving forces to achieve complex tasks, such as high power movement and multi-structure assembly, across a broad range of size scales. The materials that enable these achievements often rely upon the integration of phases that allow for internal transport, elastic energy storage, system protecting dissipation, and tunable sensitivity to interfacial interactions. Accordingly, polymer gels, which combine liquid phases with shear-sustaining macromolecular network structures, offer a robust materials platform for transferring lessons from nature into synthetic engineered devices. Here, we describe two examples from our research group of how to take advantage of mesoscale structural asymmetry, mechanics, liquid transport, and interfacial interactions to achieve new engineered capabilities. The first example takes inspiration from multiple examples in nature, including mantis shrimp and trap-jaw ants, that use Latch-Mediated Spring Actuation (LaMSA) to achieve high power, impulsive movements. We demonstrate how transient metastable deformations associated with swelling and deswelling of a polymer gel can be exploited to generate mechanical bi-stability, giving rise to multiple, self-repeating, snap-through movements. We introduce models to quantitatively describe these mechanisms and harness them to develop autonomous jumping devices. In a related manner, the second example describes the use of structural asymmetry to mediate swelling/deswelling processes and elastic restoring forces to control the motion and assembly of mesoscale polymer gel ribbons. Collectively, both examples provide new insight into how polymer gel properties, related to elasticity, diffusion, and interfacial forces, can combine with purposeful structural design to yield complex tasks, which can be used in the development of microscale robots and new adaptable composite materials.

Diverse soft metamaterials have been developed for energy-absorbing, tunable thermal expansion, soft actuator, etc. Although various functional properties of soft metamaterials have been investigated, their fatigue properties have not been studied yet, which hinders the translation of soft metamaterials into real applications. With 3D printing techniques, we control the geometrical parameters of soft metamaterials. Fracture tests and simulations are conducted to measure the S-N curve of a single printing filament and fatigue threshold of 3D printed soft metamaterials. We show that the fatigue threshold of soft metamaterials is linearly proportional to the fiber's diameter and strain energy density limit, but independent of its length. Constitutive relation of the materials and geometrical shapes determine the prefactor of such proportion relations. The results are intrinsically different from the classical Lake-Thomas theory for polymer networks, leading to a generalized theory for predicting soft metamaterials' fatigue threshold. The capability of the theory correlating the fatigue property of a single filament and entire topological networks is critical for the design of durable soft metamaterials. This theory inspires us to manufacture sinusoidal structure metamaterials, whose fatigue threshold increase dramatically.

Water scarcity has been an increasingly severe threat to our society. Solar vapor generation provides a sustainable means for desalination and water purification technologies. With highly tunable structures, unique polymer-water interactions, and ease of integration with functional materials, hydrogels show great potential for efficient solar water purification. The rational design and engineering of hydrogel surfaces have a substantial impact on the interfacial solar water vaporization process. Here, we will discuss effective ways to tailor the surface topography and wetting states of hydrogel solar evaporators to accelerate the solar vapor generation rate. Specifically, the nanotextured topography of the surface can be fabricated by a liquid-liquid interface-guided gelation process, resulting in an increased heat flux at the sharply dimpled hydrogel-air interface. In addition, hydrogel evaporators with inhomogeneous surface wettability demonstrate an ultrahigh evaporation rate with synergistic contributions from both wetting regions. Molecular dynamics simulation reveals the surface-modulated escaping behavior of water molecules. By applying hydrophilic polymers as building blocks, the hydrogel evaporators have been endowed with multifunctionalities, such as antifouling and complex contaminants removal, to improve both quantity and quality of collected water. Together with an easy-to-employ and portable purification prototype, hydrogels are an emerging materials platform for high-performance yet cost-effective water purification applications.

Hydrogel based soft materials with chemical functionalities that allow controlled degradation of the polymer are utilized as active stimuli responsive platforms for numerous applications. As one example, a hydrogel with multiple degradable functional groups that degrade in response to different wavelengths of light enables sequential release of drugs from the network. Herein, we present Dissipative Particle Dynamics (DPD) based simulations of degradation in tetra-arm polyethylene glycol (tetra-PEG [1]) hydrogels. Controlled degradation can be introduced in these gels via several chemical pathways [2,3]. In our DPD model we use the modified segmental repulsive potential (mSRP [4]) to avoid unphysical polymer chain crossing and we first establish model parameters that mimic the hydrophilicity of PEG. Further, we use our recently developed framework [5] to introduce controlled degradation in these gels and measure the fraction of degradable bonds intact during degradation. Our method allows modeling of first order degradation kinetics in these gels. We track the evolution of mass loss from bulk degrading gels and note the occurrence of a slow mass loss regime due to erosion followed by a fast regime due to reverse gelation of the polymer network. We quantify the reverse gel point of these gels by tracking the size of the second largest cluster during degradation. We focus on the effect of finite size on mass loss and reverse gel point calculations and compare these effects with previously developed scaling [6]. The reverse gel point for tetra-PEG hydrogels measured from our simulations corresponds well with the value obtained from percolation theory on a diamond lattice.

References:
1. Sakai, T., Matsunaga, T., Yamamoto, Y., Ito, C., Yoshida, R., Suzuki, S., Sasaki, N., Shibayama, M., & Chung, U. I. (2008). Design and fabrication of a high-strength hydrogel with ideally homogeneous network structure from tetrahedron-like macromonomers. Macromolecules, 41(14), 5379-5384.
2. Li, X., Tsutsui, Y., Matsunaga, T., Shibayama, M., Chung, U. I., & Sakai, T. (2011). Precise control and prediction of hydrogel degradation behavior. Macromolecules, 44(9), 3567-3571.
3. Azagarsamy, M. A., McKinnon, D. D., Alge, D. L., & Anseth, K. S. (2014). Coumarin-based photodegradable hydrogel: Design, synthesis, gelation, and degradation kinetics. ACS Macro Letters, 3(6), 515-519.
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5. Palkar, V., Choudhury, C. K., & Kuksenok, O. (2020). Development of Dissipative Particle Dynamics framework for modeling hydrogels with degradable bonds. MRS Advances, 5(17), 927-934.
6. Lin, T. S., Wang, R., Johnson, J. A., & Olsen, B. D. (2018). Topological structure of networks formed from symmetric four-arm precursors. Macromolecules, 51(3), 1224-1231.