The swelling and mechanical properties of networks are intimately tied together through the free energy function as it is affected either by chain stretching (elastic free energy) or through the mixing of the polymer with the solvent (usually through a Flory-Huggins estimate). Frenkel, then Flory and Rehner (FFR) developed a simple way of looking at this problem by simply balancing the elastic and mixing contributions to the chemical potential at swelling equilibrium. Much work has been done to examine this model, often in a way that suggests that something is missing or that the model itself is incorrect. In this presentation we examine the FFR model and show that it is correct for polymer networks swollen in organic liquids. We demonstrate that anomalous peaks in the swelling activity parameter S (or dilational modulus) are artifacts of experimental methods and we further show that, once the peak in S is removed, quantitative agreement is obtained between mixing and elastic contributions to the free energy with the simple addition of a cross-link dependent interaction parameter.

Slide-ring (SR) gels with movable cross-links along network strands have received much attention as a novel class of polymer gels. The network topology of SR gels is variable in response to imposed stress or deformation whereas that of classical gels with fixed cross-links is invariable. The polyrotaxane-based SR gels are synthesized by intermolecular cross-linking of alpha-cyclodextrin contained in poly(ethylene glycol). The SR gels are expected to exhibit novel properties and functions resulting from the movable cross-links. In this talk, we focus on the fluid-permeation behavior of the membranes of SR gels under imposed pressure (p), and the nonlinear elasticity revealed by biaxial stretching. It has been well known that the fluid permeation of classical gels obeys the Darcy's law: The steady-state fluid velocity (v) is linearly proportional to p. The proportionality constant (f) corresponding to the friction coefficient between gel network and fluid is independent of p for the classical gels. Here, we demonstrate that the membranes of SR gels exhibit a peculiar p dependence of f, where f sharply varies between two different values within a narrow p range. It indicates that SR gels are promising polymer membrane materials that enable the on-off control of fluid permeation by imposed pressure, which can be developed to separation membranes and drug delivery systems with novel functions. Further, we show a unique feature in nonlinear elasticity for SR gels revealed by the experiments using unequal biaxial strains. The effect of the strain in one direction on the stress in the other direction in SR gels is much smaller than that in classical gels. This feature results in no explicit strain-coupling term in the strain energy density function of SR gels.

Recently, we have developed a novel gel system (Tetra-PEG gel) by new network formation method, “AB-type crosslink-coupling”; the network is formed by the combination of two mutually reactive tetra-arm prepolymers with same shape. Our previous study revealed that the Tetra-PEG gel has a homogeneous polymer network with small amount of structural defects. Although the connectivity and spatial heterogeneity was observed, the degree of heterogeneity is extremely smaller than that of conventional gels. In this study, we focus on the correlation between mechanical properties and structural parameters of polymer gels. We tuned the structural parameters including the polymer volume fraction (f_0), polymerization degree of network strands (M = 5k-40k g/mol), and reaction conversion (p). We investigated the values of p by infrared (IR) measurement, elastic modulus (G) and ultimate elongation ratio (lambda;max) by stretching measurement, and fracture energy (T0) by tearing measurement.
First, we compared G measured by a stretching measurement, and that predicted from the reaction efficiency (p) using affine (G_af ) and phantom (G_ph) network models. As for the 10k and 20k Tetra-PEG gels, G_ph and G corresponded well with each other in a wider range than the other gels, suggesting that their elasticities is roughly predicted by the phantom network model. As for the 5k Tetra-PEG gel, the downward deviation of G from G_ph was increasingly pronounced with decreasing f_0. On the other hand, the 40k Tetra-PEG gel shows distinct behavior; G was above G_ph and near G_af. In order to discuss the whole tendency, G/G_af was plotted against f_0/ f*, f* is the overlapping polymer volume fraction of the prepolymer. In this figure, all of the data fall onto a single curve. In the range from f* to 3.0f*, the elastic moduli were well predicted by the phantom network model. The downward deviation below f* is due to the formation of elastically ineffective loops. In the range above 3.0f*, G = G_af increased with an increase in f_0 and approached to 1.0. This data strongly suggests that trapped entanglements are introduced to the network or that the model shifts to the affne network model, or both in the region above 3.0f*. Only from these results, we cannot distinguish whether the deviation from the phantom network model prediction is originated from trapped entanglements or from the change in models. Thus, we investigate the trapped entanglements by the tearing measurement. The results in tearing measurement indicated that there are few trapped entanglements. Taking into account these data, it is strongly suggested that the model predicting the elastic modulus shifts model with increasing _0 and N. In the presentation, the results of ultimate elongation ratio will be also discussed.

Responsively tough, injectable biomaterials are potentially useful for the minimally-invasive surgical implantation of durable matrices, either for delivering cellular or molecular cargo, or to act as robust fillers for soft tissue reinforcement. Associative protein hydrogels are well-suited for use as injectable materials, exhibiting cyto-protective shear-banding behavior and immediate recovery post-injection. However, the low yield stress required for the injectability of these materials is typically incompatible with the high resistance to deformation and fracture that is needed to maintain implant integrity under physiological stresses. One approach to accomplish both injectability and toughness is to engineer a shear thinning hydrogel with a low yield stress at low temperatures that is reinforced at body temperature due to thermoresponsive block copolymer self-assembly. Toward this end, triblock copolymer hydrogels containing artificially engineered associative protein midblocks and poly(N-isopropylacrylamide) (PNIPAM) endblocks have been developed, exhibiting responsive and reversible toughening over clinically-relevant temperature ranges. The PNIPAM endblocks exhibit lower critical solution behavior in this hybrid protein-polymer gel, and heating above the transition temperature to 37°C leads to endblock desolvation and aggregation into nanoscale domains. The formation of these reinforcing domains leads to large increases in the gel&’s elastic modulus and yield stress in shear, as well as improved resistance to compressive failure, erosion, and creep. The relationship between macromolecular design, nanostructure formation, and gel mechanics has been investigated in detail using small-angle neutron scattering (SANS) and oscillatory shear rheology, revealing important principles for controlling network self-assembly and achieving improved reinforcement. In particular, large micellar cores, high PNIPAM volume fractions, and high densities of midblock associations led to the stiffest hydrogels, with elastic moduli reinforced by a factor of 14 to approximately 130 kPa at 37°C. Stress relaxation times were seen to increase by up to 50-fold for gels with the largest micelles and packing fractions. For large enough endblocks, midblock associations were seen to promote endblock segregation even below the PNIPAM transition temperature, and these swollen micellar structures introduced long relaxation times into the gels. These studies demonstrate that control of the double network structure is critical for tuning the gel&’s mechanical behavior over a broad range for use in various biomedical applications.

We propose here a generic method to reinforce weak elastomers without using fillers. This method could be particularly interesting in the biomedical or high tech applications where pure polymers with specific physical properties (transparency, resistance to UV or temperature) are used but have poor mechanical properties.
In recent studies on the reinforement of hydrogels. Gong et al have shown that hydrogels synthesized with two interpenetrating networks with very different levels of crosslinking and conformations of chains have a fracture toughness significantly enhanced relative to a single homogeneous network[1][2][3]. Their mechanical properties are enhanced through breaking the bonds of the more crosslinked and highly stretched minority network while avoiding crack propagation through the less crosslinked and unstreched majority network[4].
We applied this method to acrylic elastomers and succesfully prepared poly(alkyl acrylate) elastomers containing isotropically prestretched chains at different volume fractions, using sequential swelling/polymerization steps. Samples containing prestretched chains show an impressive enhancement of properties compared to networks polymerized in one step. Both initial modulus and fracture toughness are enhanced while retaining a negligible hysteresis and residual deformation upon unloading, which is impossible in simple networks.. Our best samples show a 50 time increase in true stress at break and in fracture toughness, making those material as tough as some filled elastomers. Our methodology holds great promise to improve the extensibility, toughness and tune the non-linear elasticity of elastomers previously thought to be mechanically too weak to be used in mechanically demanding applications.

[1] Gong, J. P.; et al, Y. Adv. Mater. 2003, 15, 1155-1158.
[2] Tanaka, Y.; et al J. of Physical Chemistry B 2005, 109, 11559-11562.
[3] Gong, J. P. Soft Matter 2010, 6, 2583.
[4] Brown, H. R. Macromolecules 2007, 40, 3815-3818.

We investigated the effects of swelling and deswelling on the mechanical properties of Tetra-PEG ion gels with variable polymer volume fractions at the measured condition (phi;_m). Tetra-PEG gels were prepared by the AB type crosslink-coupling between the two symmetrical tetra-arm prepolymers with tuning the network strands length and polymer volume fractions. The use of an ionic liquid as diluent enables us to measure the mechanical properties of strongly deswollen Tetra-PEG gels above the melting point of PEG. The drastic increase in the elastic modulus was observed in the high phi;_m region due to the unusually contracted conformation of the network strands, called supercoiling. The Obukhov model, which predicts the elasticity of polymer networks using the concentration at preparation (phi;_0) and measured condition (phi;_m) as variables, can describe the phi;m-dependence of the elastic modulus in all phi;_m regions. Furthermore, we analyzed the stress-elongation relationships for the swollen and deswollen networks. We estimated the fractal dimensions based on the Pincus blob concept. We, for the first time, observed the crossover of the phi;_m-dependence of the fractal dimension from normal scaling to supercoiling, and the dependence of the fractal dimension on the strand length. The extensibility at break increased with an increase in phi;_m and an increase in the network strand length. These results did not obey the familiar Kuhn model, but were better explained by our model. These findings will help to understand the structure and formation mechanism of supercoiling.

The piezoelectric-rubber is expected to be a material that is used at the places where conventional piezoelectric materials cannot be applied, because it has flexibility and can be formed into arbitrary shape. However, so far there have been the following issues that in order to increase the piezoelectric property of piezoelectric-rubber, a large amount of the large size piezoelectric-ceramic particles must be mixed in the rubber, resulting in loss of the elastic property of the piezoelectric-rubber.
In the previous investigation, it was confirmed that the orientation of the piezoelectric-ceramic particles in the direction normal to the surface of the rubber was effective in increasing d33 which indicates the piezoelectric coefficient when the input load is applied and the output electric charge is taken both in the direction of thickness of rubber. On the other hand, it is considered that the piezoelectric property of the “Oriented-Type” in which the piezoelectric-ceramic particles is oriented in the rubber is strongly affected by rubber&’s property as the matrix of the Oriented-type, because the volume of the rubber of Oriented-type is larger than that of the PZT particles and the stress on the oriented particles is affected by the property of matrix.
Therefore the influence of the matrix property on piezoelectric property of Oriented-Type was investigated. In the investigation, the Young&’s modulus of matrix was focused as the matrix property. The lower the Young&’s modulus of matrix is, the higher d33 of Oriented-Type is, because the stress applied to oriented PZT particles in Oriented-type increases. Four kinds of matrix materials were investigated: Silicone gel, Silicone rubber, Urethane rubber and Poly-methyl-methacrylate. The Young&’s modulus of matrix materials are as follows: Silicone gel is 5MPa; Silicone rubber, 70 MPa; Urethane rubber, 180MPa; and Poly-methyl-methacrylate, 600MPa. The piezoelectric-ceramic particles to be mixed with the matrix materials are the same particles of Lead Zirconate Titanate (PZT).
As the result of investigation, the sample made of the silicone gel which had the lowest Yang&’s modulus in the selected matrix materials had the largest d33. The large increase as compared with the previous investigation was observed. The d33 of the fabricated sample was more than 60 pC/N when the concentration of PZT particle was about 10 Vol%. The Oriented-type using silicone gel as matrix is expected to be the vibration-isolating materials having the property of sensor, because the volume of silicone gel is 90 Vol% and Young&’s modulus is 12MPa even if the sample is the piezoelectric-rubber of Oriented-Type.

Poly(N-isopropylacrylamide) (PNIPAM) is a thermosensitive polymer that is well-known for its lower critical solution temperature (LCST) around 305K. Below the LCST, PNIPAM is soluble in water and above this temperature polymer chains collapse prior to aggregation. In the presence of methanol, experiments suggest that, LCST of PNIPAM is depressed up to certain mole fraction of methanol (0.35 mole fractions) and it is speculated that addition of methanol affects the PNIPAM-water interactions. Above 0.35 moles fraction of methanol, LCST gets elevated to temperatures above 32°C and cannot be detected up to 100°C. In the present study we have used MD simulations to investigate the effect of solvent mixed with methanol on conformational transitions and the LCST of PNIPAM. We employ polymer consistent force-field (PCFF) and CHARMM force-field to study the PNIPAM and water-methanol mixtures of different mole fractions of methanol namely, 0.018, 0.09, 0.27, 0.5, and 0.98 mole fractions, at fully atomistic level were carried out at 260, 278, 310, and 340 K. Simulated trajectories were analyzed for different structural properties such as radius of gyration of PNIPAM, extent of hydration of PNIPAM etc. Different dynamical properties such as diffusion coefficient, hydrogen bonding life-times, residence time of water and methanol near PNIPAM were also studied at 260, 278, 310, and 340 K.

Natural Rubber latex (NRL) is a colloidal system constituted of rubber particles (20-45%) ranging from 3 nm to 5 µm dispersed in a liquid serum [1]. The NRL has bioactive properties that have recently been explored to produce films using polyelectrolyte multilayers technique [2]. However, the production of homogenous films may be influenced by the distribution of rubber particles size. In this sense, we separated the NRL to keep structures bellow 200 nm, aiming the production of homogeneous thin films using layer-by-layer technique. The separation of NRL occurred by a sequence of centrifugations. First centrifugation at 12,225 G (9,000rpm) for 2h removed the bigger particles; followed by a sequence of 3 centrifugations at 42,206 G (22,000 rpm) for 1h. On each step the liquid on the bottom was collected and submitted to the next centrifugation step. By this mean, the NRL was reduced in 75% of the initial weight. This serum was finally filtrated in 0.2 µm membrane and the solution obtained was analyzed. The presence of poly-cis-isoprene in the sample was confirmed by FTIR peaks attributed to CH2 (2858, 2926 cm-1), CH3 (2964 cm-1), C=C (1664 cm-1) and C=CH (840 cm-1). The presence of proteins was confirmed by the FTIR peaks of C=O (1737 cm-1), C-O (1099 cm-1), O-O (1013 cm-1) and NH (1580 cm-1). Furthermore, there is a broad peak at 3330 cm-1 that indicates the presence of both NRL (=CH, 3033 cm-1) and proteins (N-H 3280 cm-1 and -OH, 3440 cm-1) [3]. The presence of proteins together with rubber nanoparticles was also detected by field-flow fractionation with asymmetric cross-flow (FFF). Besides, the separated material was evaluated by dynamic light scattering (DLS) revealing sizes of 40 to 220 nm and zeta potential of -46 mV. However, only particles smaller than 70 nm were identified in AFM images of the NRL deposited on polyethylenimine (PEI) layer. The NRL layer immobilized on surface was 3 nm thick when analyzed by ellipsometry, which was similar to the height of the structures detected by AFM. Therefore, it can be concluded that nano-sized natural rubber particles remain on the serum after centrifugation.
1. d'Auzac, J., J.-L. Jacob, and H. Chrestin, Physiology of rubber tree latex. 1989, Boca Raton: CRC press, Inc. 488.
2. Davi, C.P., et al., Natural rubber latex LbL films: Characterization and growth of fibroblasts. Journal of Applied Polymer Science, 2012. 125(3): p. 2137-2147.
3. Rippel, M.M., et al., Skim and cream natural rubber particles: colloidal properties, coalescence and film formation. Journal of Colloid and Interface Science, 2003. 268(2): p. 330-340.

In previous studies, pH-sensitive and ionic-strength-sensitive hydrogels have been produced by adding pendant acidic or basic functional groups to the polymer chains. These hydrogels swell/shrink in response to appropriate pH and ionic strength changes in aqueous media. The swelling/shrinking properties of these hydrogels are depended on electrostatic repulsion. Generally, these hydrogels containing weakly ionic groups, such as carboxylic groups and amino groups, swell/shrink reversibly in response to pH because the dissociation state of these functional groups change to pH. We expected that the strongly ionic groups such as a sulfonic acid and alky ammonium should be suitable for novel hydrogels enabling the fairly swelling/shrinking characteristics at wider pH range.
In this study, we aim to develop a novel pH- and molecular-sensitive hydrogels which is prepared with copolymerization of ionic functional monomers and PEG-based crosslinker having good thermal/pH stability and high mobility. We evaluated the water adsorption ability of various PEG-based hydrogels by changing the molecular weight of PEG-dimethacrylate (PEG-DMA) as a crosslinker, porogenic solvents and its compositions. Moreover, we evaluated the specific swelling/shrinking based on the molecular recognition by measuring the volume change of PEG-based hydrogels toward various ionic compounds. Additionally, we examined the drastic volume change of the hydrogels by dual interactions containing ionic interactions of hydrogels-solutes and hydrophobic interactions of solutes-solutes which were adsorbed onto the hydrogels.

One of the ultimate goals of polymer science is to understand the relationship between the structure and the physical properties of hydrogels. Recently, we developed a near-ideal network, Tetra-PEG gel, which is formed by the combination of two mutually reactive tetra-arm prepolymers with the same shape. Our previous study determined the exact models that predict the relationship between the structural parameters and the physical properties of Tetra-PEG gels. In contrast, the mechanical properties of conventional hydrogels remain difficult to predict because conventional hydrogels have a significant degree of the heterogeneity. The heterogeneities are categorized into spatial, connectivity and topological heterogeneities. These heterogeneities relate with each other and make variety of substructures in polymer network, which complicates the structural parameters and mechanical properties. In this study, we focused on one of the simplest heterogeneities (i.e., mesh size heterogeneity) and investigated the influence on physical properties. We prepared Tetra-PEG gels with bimodal distribution in strand length (Tetra-PEG bimodal gels) by combining different molecular weight of Tetra-PEG prepolymers, and measured the physical properties of the hydrogels (elastic modulus, and maximum deformation, and fracture energy). The samples formed above the overlapping concentration of prepolymers had few heterogeneities regardless of heterogeneous distribution in strand length. The physical properties of Tetra-PEG bimodal gels were also well described by the models for conventional Tetra-PEG gels with the average of polymerization degree between crosslinks and initial volume fraction. We conclude that the mechanical properties of hydrogels that have heterogeneous distribution in strand length can be predicted from the average strand length in the range of this study.

[Introduction]
We have investigated poly(vinyl alcohol) (PVA) hydrogel as a biomaterial for a replacement for artificial articular cartilage because of its excellent mechanical properties, biocompatibility, and low friction coefficient.
Generally, PVA hydrogels is physical gels with small crystalline as crosslinking points and have been prepared by low temperature crystallization method. When water is used as a sole solvent during freezing, phase separation into a PVA-poor and PVA-rich phase may take place, resulting in PVA crystallization in the phase separated state to give a translucent weak hydrogel.
In order to make PVA hydrogel having high mechanical properties, a mixed solvent of dimethyl sulfoxide (DMSO) and water should be used to prevent freezing of the solvent and phase separation during freezing. Such hydrogel is transparent and has high mechanical properties. But DMSO has toxicity, and it also has the effect of accelerating the absorption of harmful substances.
Therefore, in this study, we intended to eliminate DMSO in the process to make PVA hydrogel with high mechanical properties.
[Material and methods]
PVA hydrogels were prepared by low temperature crystallization with DMSO method and novel heat pressing method. In low temperature crystallization method, PVA (Japan VAM & POVAL Co. Ltd., degree of polymerization 1700, degree of saponification 99.7%) was dissolved in a solvent mixture of DMSO and H2O with weight ratio of 80/20 at 120 C at a concentration of 10w/w%. The solution was poured into a mold and cooled to -20 C for 24h. In heat pressing method, PVA was mixed with same weight of H2O (50w/w%). The swollen PVA/H2O was pressed at 0~20MPa and 90C for 30 min.
[Results and discussion]
PVA hydrogels from a highly concentrated aqueous solution was prepared by a heat pressing method. By this method, transparent PVA hydrogels can be obtained because of the fast crystallization, even at room temperature. And water content was well controlled by heating of dried gel due to the increasing of crystallinity. Fourier transform infrared spectroscopy (FTIR) and dynamic mechanical analysis (DMA) measurement revealed that heat pressing PVA hydrogel with only water showed slower crystallization and gelation than DMSO containing hydrogels. Small angle X-ray scattering (SAXS) shows all PVA hydrogel has a microcrystalline structure, showed quite similar structure of both low temperature crystallization and heat pressing hydrogels. The mechanical properties of PVA hydrogels were remarkably dependent on their water contents after gelation, regardless of the preparation method. It was concluded that successfully we were able to make PVA hydrogel with high mechanical properties by a heat pressing method without using DMSO.

We report unique methodologies for the construction of supramolecular fluorescent dendron nanotubes of which the surface is covered with cyclodextrins (CDs). In particular, their sensory characterisctics will be discussed.
The organic nanotubes with unique fluorescence characteristics were fabricated by self-assembly of the amide dendrons and cyclodextrins (CDs). In addition, the electron transfer property of the hybrid array of the nanotubes with metal nanoparticles was utilized for sensory application. The dendritic building blocks with focal pyrene unit self-organize into vesicles in aqueous phase. The in-situ inclusion of the focal pyrene units into the cavity of β- or γ-CD induced formation of self-assembled fluorescent nanotubes. The surface of the nanotube is covered with CDs. Therefore, the functional group on the surface of the nanotube is controlled precisely by modifying the functionality of CD. This work provides an efficient methodology not only to create a new class of CD-covered organic nanotubes. The hybrid array of the tubes with Au nanoparticles can be conveniently prepared by using the interaction of the surface functionality of the tube with that of Au nanoparticle. The electron transfer from the organic nanotube to Au nanoparticle induces fluorescence quenching which can be effectively utilized for sensing application. In this work, biosensory characteristics of the dendron-CD nanotube was demonstrated representatively by using the strepavidin-biotin system. In addition, we demonstrated that dendron-CD nanotube can be an efficient metal sensory platform by introducing coumarin-Gly-His (GH) dipeptide unit onto the surface of the nanotube.

A novel three-dimensionally ordered macroporous (3DOM) hydrogel with immobilized-enzyme was synthesized, characterized, and used for protein digestion. The 3DOM hydrogel was prepared by the copolymerization of poly(ethylene glycol) methacrylate (PEOMA) and poly(ethylene oxide) dimethacrylate (PEODMA) in the presence of latex colloidal crystal as the template. The colloidal crystal was synthesized by surfactant-free emulsion polymerization, and has a uniform pore size typically in the range of 100-1000 nm. After being used as the sacrificing template, the colloidal crystal was dissolved in acetone to generate the 3D ordered macropores with interconnected windows in the crosslinked hydrogel, which facilitated the liquid transport through the pores. The trypsin was introduced onto the pore surfaces through condensation reactions. The structure of the functionalized 3DOM hydrogel was characterized by scanning electron microscopy (SEM) and nanoscale 3D X-ray microscopy (XRM). It was demonstrated that the porous structure of the hydrogel was able to undergo reversible shrinkage and expansion by drying and swelling. The trypsin-immobilized hydrogel was loaded in a column and showed high activity for enzyme digestion when an aqueous solution of Nα-benzoyl-L-arginine p-nitroanilide (BAPNA) or bovine serum albumin (BSA) passing through it. This study indicates that the colloidal crystal templated 3DOM hydrogel is a useful enzyme immobilization substrate for protein digestion.

I am characterizing structural changes that arise in the polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) amphiphilic triblock copolymers (commercially known as Pluronics) as a function of temperature through Differential Scanning Calorimetry (DSC). Pluronic® P-105 (BASF Corp) (Mw = 6.5Kg/mol) has been evaluated most extensively. I am also measuring how adding small amounts of Methyl Paraben (MP) perturb the structure and the driving force for micelle formation in aqueous PEO-PPO-PEO solutions with different block lengths. Micelle formation is an aggregate of surfactant molecules dispersed in solution. Hydrophilic heads interact with surrounding aqueous solvent while hydrophobic tails form the micelle center. This new evolving structure can be resolved by Differential Scanning Calorimetry (DSC). DSC is a thermo analytical technique where the difference in the amount of heat required to increase the temperature of a sample and a reference is tracked with temperature. Methyl Paraben is commonly used as preservatives by the cosmetic and pharmaceutical industries. It is found in fruits where it acts as an antimicrobial agent and kills or inhibits the growth of microorganisms. Future experiments will focus on resolving the driving force for micelle formation in the presence of drug mimics. We are ultimately trying to resolve how drugs incorporated into dispersion-based drug delivery vehicles affects their solidification characteristics when heated to body temperature.

Like cellular proteins that form fibrillar nanostructures (e.g., cytoskeletal filaments), small hydrogelator molecules self-assemble in water to generate molecular nanofibers.1 While most endogenous protein filaments are crucial for normal cellular functions (e.g., cell movements and division)2 and some have been associated with human illnesses (e.g., Alzheimer's, Pick's, and Parkinson&’s diseases),3 the mechanism of self-assembly of small molecules in the cell and the fate of intracellular molecular nanofibers remain largely unknown.4 Here we interpret the self-assembly behavior of peptide-based hydrogelators in terms of the phase diagram determined from light scattering and NMR measurements made as a function of concentration and temperature. We visualize by fluorescence imaging the enzyme-triggered self-assembly of the non-fluorescent hydrogelator with the doping method. Cell fractionation experiments, fluorescent imaging, and electron microscopy indicate that the molecular nanofibers localize to the endoplasmic reticulum (ER) and are likely processed via the cellular secretory pathway (i.e., ER-Golgi-lysosomes/secretion). This work not only provides the spatiotemporal profile of molecular nanofibers inside cells, but also may lead to a new paradigm for regulating cellular functions based on the interactions between molecular nanofibers and organelles as well as a new model system for understanding neurodegenerative diseases caused by molecular aggregates.
References:
1. Yang, Z. M.; Liang, G. L.; Xu, B. Acc. Chem. Res. 2008, 41, 315.
2. Alberts, B. Essential Cell Biology; 3rd ed.; Garland Science: New York, 2009.
3. Spillantini MG; Crowther RA; Jakes R; Hasegawa M; Goedert M. Proc. Natl. Acad. Sci. USA 1998, 95, 6469.
4. Gao, Y.; Shi, J. F.; Yuan, D.; Xu, B. Nat. Commun. 2012, 3, 1033.

Cartilage is a gel-like biological tissue consisting of solid and fluid components. The solid component is composed of a collagen network, which contains highly swollen negatively charged proteoglycan assemblies. The predominant cartilage proteoglycan is the bottle-brush shaped aggrecan. In the presence of hyaluronic acid (HA) and link protein aggrecan molecules condense on the HA chain and form a secondary bottle-brush structure. The swollen microgel-like assemblies enable cartilage to support high loads. The collagen network plays limited role in load bearing. Its principal role of is to immobilize the aggregan/HA assemblies and provide tensile stability to the cartilage.
Cartilage can be divided into three zones based on the orientation of fibers. Close to the surface, collagen fibers are aligned parallel to the articulating surface of the joint. In this region, designated as superficial zone, the collagen fibers support the tensile stresses generated when compressive loads are applied to the tissue. In the intermediate zone the collagen fibers are randomly oriented. In the deep zone, the fiber orientation is perpendicular to the bone surface. To quantify the consequences of the above morphological differences on the macroscopic properties we made elastic modulus measurements and osmotic swelling pressure measurements on the three layers. The measurements were made on bovine cartilage of a 2 year-old femur head combining atomic force microscopy with tissue-osmometry.

Physically-associating telechelic polymer networks are of particular interest not only for tissue engineering applications due to their ability to shear thin, but also as model systems for further study of network behavior under external forces. Models of these gels are based on kinetic theories of transient networks. In the 1940s, Green and Tobolsky postulated a theory for the mechanical behavior of viscoelastic materials meant to enhance classic Maxwell, Voigt, and other classical relaxation theories by looking more closely at the molecular origins of material behavior. Half a century later, Tanaka and Edwards took the ideas presented in Green and Tobolsky&’s paper and applied them to a telechelic polymer network in solution comprised of long chains with hydrophobic stickers at either end capable of forming elastically active network junctions. Most importantly, Tanaka and Edwards&’ theory incorporated mechanical dependence on deformation history. These two studies provided the basis for the more recent paper by Tripathi, Tam and McKinley, where an additional solvent drag term was added to the chain relaxation, and the presence of both dangling chains and bridging chains contribute to the final equation for the stress tensor. A limitation of current theories is that they do not enable easy tracking of the polymer chain end distribution. This ability is important for full understanding of network behavior - specifically with respect to material recovery following deformation.
We have developed a theory for polymer chain dynamics in a polymer network that models the entire chain end-to-end distribution using a Smoluchowski equation combined with force-activated transient network kinetics according to Bell&’s Law. This equation is solved numerically, calculating the response of a telechelic polymer gelator in shear flow. With this computationally simple theory, we can determine the locations and types of chain present (fraction of chains present in loops, in bridges, and as free chains) in the system under steady shear and oscillatory shear flows at equilibrium. In particular, the decrease in loop fraction at higher Deborah numbers has already given valuable insight into the creation and destruction of loops in steady shear flow. By looking at the evolution of loop, free, and bridge chain fractions over time, we can also show how the system recovers following shear. Our theory shows potential for expansion to more complex systems such as brush polymers, multiblock copolymers, and protein-polymer block copolymers.
Works Cited:
Green, M. S.; Tobolsky, A. V. The Journal of Chemical Physics 1946, 14, 80
Tanaka, F.; Edwards, S. F. Macromolecules 1992, 25, 1516.
Tripathi, A.; Tam, K. C.; McKinley, G. H. Macromolecules 2006, 39, 1981.

Photonic hydrogels are an emerging family of materials that combine periodic nanoscale ordering giving rise to Bragg-like reflection of visible light with the responsive properties of hydrogels. These composites are often based around self-assembled close-packed arrays of spherical nanoparticles, giving rise to brilliant reflected colors that changes as the hydrogel swells and contracts in response to external stimuli. Chiral nematic (CN) liquid crystalline phases can act as photonic structures due to their helical, periodic layering, and exhibit unique optical properties that are desirable in the form of a responsive hydrogel. Here, I will discuss our recent work in preparing new responsive hydrogels with photonic CN ordering through the self-assembly of cellulose nanocrystals. This approach can be considered a general route to prepare photonic hydrogels with CN ordering that respond to various external stimuli.

Solar energy conversion has been expected as one of the most urgent and promising technologies for sustainable energy production. Many types of solar cells have been developed, but unfortunately all of these solar cells have a critical disadvantage, in that the photoreceptors cannot absorb the entire photo-band of sunlight, which leads to inefficient energy conversion. A reasonable solution for this problem can be realized by applying a spectral conversion film (SCF) from unused UV-A to visible wavelengths suitable for solar cells. We demonstrate a new strategy for fabricating effective SCF, which is based on formation of a polymer/monomer phase-separated structure through self-assembling fluorophores functionalized by L-glutamide (g) as a low-molecular-weight gelator.
We prepared a g-functionalized pyrene derivative as a fluorophore (g-Pyr) according to our previously reported procedure. The g-Pyr was doped in a polymer film by a casting method from a mixed solution of g-Pyr and polymer such as polystyrene and EVA. The resultant transparent polymer film showed typical excimer emission at lambda;max = 450 nm by absorption of UV-A light while monomeric emission was observed at 350 and 380 nm. TEM and CD observations indicated that g-Pyr was phase-separated as nano-fibrillar aggregates with highly ordered stacking structures in polymer.
In this system, the emission band can be tuned by controlling the phase-separated structure of a fluorophore in polymer. For example, by changing the alkyl groups in g-unit, the emission band (lambda;max) was adjusted between 420 and 475 nm. By choosing phenyl anthracene and alkynyl anthracence derivatives as fluorophoric moieties instead of pyrene, the excimeric emission appeared at lambda;max = 480 nm and 500 nm, respectively. Moreover, it was confirmed that the emission band of g-derivatives could be controlled by the polymer composition and casting condition (concentration, solvent and temperature). As a result, when the g-Pyr-doped polystyrene film was put on the top of a compound semiconductor solar cell and the power-conversion efficiency was measured by using the solar simulator, 5 - 6 % enhancement of the power conversion efficiency was observed through matching of spectral sensitivity.

Aerogel is an open-celled, microporous, solid foam composed of a network of interconnected structures obtained either by supercritical drying or freeze-drying the wet gels to replace the solvent with air. The high aspect ratio of carbon nanotubes (CNTs) enables the formation of a percolating network at relatively low loading (< 1%). Further, integrating the intrinsic mechanical and electrical properties of CNTs with those of an aerogel provides a new class of material with unique multifunctional properties which may find applications in fuel cells, super capacitors, batteries, catalyst supports, energy absorption materials, chemical and biological sensors (Gui et al., Adv. Mater. 2010, 22, 617-621). A binder such as polyvinyl alcohol may be added to the CNT aerogels as reinforcement, but this may increase the junction resistance and result in lower thermal and electrical conductivities (Bryning et al., Adv. Mater. 2007, 19, 661-664). In this presentation, we will report our recent attempts in improving the mechanical integrity by first functionalizing the CNTs with carboxylic (-COOH) groups and subsequently cross-linking the CNTs using diamines. The density of -COOH groups on the CNTs has been carefully quantified using titration to determine an appropriate stoichiometric ratio for the amidation reactions. Preliminary results on the rheological properties of the wet gels during cross-linking and the mechanical properties of the final CNT aerogels will also be presented.

Multi-sensitive microgels have special properties that can be controlled via the chemical composition as well as the morphology of the particle. [1] Core-shell microgels are used as templates for the formation of more complex structures. Dissolution of the core leads to hollow microgel particles the structure of which depends on the type of the core. Particles with temperature dependent spherical or anisotropic shape can be prepared, thus shape transitions can be induced. Small angle neutron scattering employing contrast variation provides detailed information on the structure of the hollow microgels.
Microgels can also be employed as responsive template for the formation of stable polyelectrolyte complexes. We will first discuss the influence of charge distribution inside microgels on their properties. Then we will show how microgels with different morphology can be used for the formation of polyelectrolyte complexes and as substrate for polyelectrolyte multilayers.
[1] Richtering, W.; Pich, A. The special behaviours of responsive core-shell nanogels. Soft Matter 2012, 8, 11423-11430.

Microgels are hydrogel particles with micron and sub-micron diameters. They have been developed, studied, and exploited for a broad range of applications because of their unique combination of size, soft mechanical properties, and controllable network properties. We have been using microgels to modulate the properties of biomaterials surfaces to differentially control their interactions with tissue cells and bacteria. The long-term goal is to create biomaterials that promote healing while simultaneously inhibiting infection. Because poly(ethylene glycol) [PEG] is used in a number of FDA-approved products and has well-known antifouling properties, we work primarily with PEG-based microgels. We render these anionic either by copolymerization with monomeric acids or by blending with polyacids during suspension photopolymerization. Both methods produce pH-dependent negative charge. Surfaces, both planar 2-D surfaces as well as topographically complex 3-D surfaces, can be modified using a hierarchy of non-line-of-sight electrostatic deposition processes that create biomaterials surfaces whose cell adhesiveness is modulated by a sub-monolayer of microgels. Average inter-microgel spacings of 1-2 microns exploit natural differences between staphylococcal bacteria and tissue cells, which open the opportunity to differentially control surfaces interactions with them. After deposition, the microgels can be loaded with a variety of small-molecule, cationic antimicrobials. The details of loading depend on the relative sizes of the antimicrobials and the microgel network structure as well as on the amount and spatial distribution of electrostatic charge within both the microgel and the antimicrobials. The exposed surface between microgels can be further modified by the adsorption of adhesion-promoting proteins such as fibronectin again by electrostatic interaction. This approach combines a rich interplay of microgel structure and chemistry as a key component in a simple and translatable approach to differentially modulate the surface properties of next-generation biomaterials.

Nanocomposites based on synthetic polymers grafted from kraft lignin with average particle size of 5 nm were synthesized using atom transfer radical polymerization. Lignin macroinitiators were prepared at average numbers densities of 2, 7, and 16 per lignin particle, and polystyrene and poly(methyl methacrylate) were grafted from the particles using atom transfer radical polymerization. Tensile testing of the samples showed a decreased modulus but enhanced toughness of all nanocomposites compared to unfilled homopolymers, but the poly(methyl methacrylate)-grafted samples had nearly twice the ultimate elongation as the polystyrene grafts at high graft density. Both types of grafted nanocomposites had toughness values that were 20 times that of the corresponding blend, indicating the importance of the grafted architecture in achieving these mechanical properties. Dynamical mechanical analysis was used to measure softening temperatures, and both the polystyrene-grafted and poly(methyl methacrylate)-grafted nanocomposites had a peak in the loss modulus that was higher than the corresponding homopolymer, consistent with strong polymer-lignin interactions. Polymer-grafted lignin could be an important structural material based on an inexpensive, renewable feedstock that offers unique mechanical properties compared with many other nanocomposites based on inorganic nanoparticles.

Polymersomes are vesicles consisting of amphiphilic block-co-polymers; they are well suited delivery vehicles. They are typically formed using re-hydration techniques where block-co-polymers self-assemble into vesicular structures. However, only certain types of block-co-polymers self-assemble into these structures; this precludes the incorporation of many different types of block-co-polymers into the vesicular membranes. Polymersomes can also be formed through microfluidic techniques. This assembly route uses double emulsion templates to form vesicles; it therefore enables the incorporation of amphiphilic molecules into the polymersome membrane that would not spontaneously assemble into vesicular structures. It allows us to design thermo-responsive polymersomes by incorporating thermo-responsive block-co-polymers into the vesicular membrane. These vesicles can be further converted into photo-responsive polymersomes by incorporating hydrophobic gold nanoparticles into the polymersome membrane. The resulting photo-responsive polymersomes enable triggered release of encapsulants through laser irradiation.

Reversible shift of the pKa/pKb value of acids/base in enzymes plays a crucial role in their functions. For instance, binding of oxygen to hemoglobin induces drastic conformation change of the protein, lowering pKa of ammonium and imidazolium cations in/on the proteins. The shift of pKa induces release of protons from hemoglobin, pushing out bicarbonate ions from blood effectively. Recently, we have reported that temperature responsive gel particles which contains amine groups, reversibly absorbs CO2 in the response of temperature-induced volume phase transition. Conformation change of pNIPAm induced by the phase transition lowered dielectric constant around the ammonium cations in the particles, resulting significant decrease of pKa. The shift of pKa results in release of protons from the NPs, pushing out CO2 from the solution. However, general guidelines to prepare NPs with large pKa shift have not been revealed. In this study, we report that nanoparticles that show large pKa shift can be prepared by copolymerizing N-isopropyl acrylamide and acrylic acid in the presence of proton as a template.

Polyelectrolyte multilayers (PEMs) that contain an excess of amines are known to swell and shrink significantly and repeatably in response to changes in ambient pH. Nanoparticles can be incorporated onto and into such films, and can then be actuated by the swelling and shrinking of the films. Such structures are of interest for applications in areas such as photonics and biosensing, and can also be used to probe the properties of the film itself. We report on a series of such experiments, where the vertical position of particles was determined to high accuracy either through fluorescent lifetime measurements or by what is known as a plasmon nanoruler. With these methods, we can dynamically monitor the film thickness, and have for instance been able to show that while thicker PEMs tend to switch abruptly between discrete thicknesses while exhibiting large hysteresis, thin films consisting of a single polycation layer instead vary smoothly in thickness with pH, showing a minimum of hysteresis. These same techniques can also be used to study the interaction between a surface and a PEM. For example, when larger charged particles are combined with a PEM, Coulomb forces embed the particles into the body of the film, so that the gap between particle and surface is only a fraction of the unstrained film thickness. Although the film is highly mechanically compliant, this gap can nonetheless be reliably modulated with pH, so that relatively thick amine-rich PEMs can be used to dynamically tune distance of only a few nm or less.

In this research, we show that poly(vinyl alcohol) (PVA), a synthetic water-soluble polymer with wide ranging attributes including, a high level of biocompatibility, and ease of chemical functionalization and cross-linking, can be successfully assembled into a multilayer thin film by hydrogen bonding interactions. The presence of hydroxyls group in PVA allows hydrogen bonding with carboxylic acid groups present in weak polyacids such as poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) at low pH conditions. Among the systems investigated, PVA/PAA multilayers functionalized with poly(ethylene glycol methyl ether) (PEG) exhibited two interesting characteristics: one is zwitter-wettable behavior whereby the multilayer film exhibits a facile, rapid absorption of water from the gas phase while simultaneously exhibiting very high contact angles for drops of liquid water placed on the surface. The second notable characteristic of these films is their transient water contact angle behavior. Time-dependent wetting behavior of these coatings results from the surface rearrangement of hydrophilic functional groups towards the surface in response to exposure to a liquid water environment and has been assessed by both goniometry and dynamic tensiometry. Also, the zwitter-wettable behavior and its use in antifrost and antifogging coatings have been investigated in detail.

An ideal drug delivery system (DDS) is expected to satisfy the conflicting requirements of high stability in extracellular fluid during the in vivo circulation, however, being labile after targeting to a desirable site, followed with the release of therapeutic agents. The aim of this communication is to present original results on reversibly crosslinked (RCL) nanogels as a new DDS, consisting of thermo-responsive copolymer of poly(vinyl alcohol)-b-poly(N-vinylcaprolactam) and boronate-functionalized maghemite nanoparticles. These multifunctional RCL nanogels were constructed via the reversible boronate/diols bonding strategy, and found to combine all these properties:
(i) Significantly improved stability under physiological pH (7.4) in aqueous medium, compared to that of phenylboronic acid-crosslinked nanostructures reported before;
(ii) Minimal premature drug release (< 8% in 24 h) was found at physiological condition (5 mM glucose, pH 7.4); however, triggered release was observed upon exposure to acidic pH (6.0 or 5.0) and/or presence of glucose;
(iii) Magnetically-induced local heating could be generated under alternative magnetic field (AMF, 755 kHz, 14 mT), and AMF application could also contribute to an accelerated release, while with a mild heating to the release medium (< 1°C). Moreover, enhanced T2-weighted contrast performance was also observed;
(iv) Cytotoxicity against fibroblastic L929 and melanoma MEL-5 cell lines disclosed a good biocompatibility of these RCL nanogels. In vitro pH- and/or glucose-triggered drug release of tamoxifen with the cell culture was evidenced with the enhanced cell-proliferation inhibition and cleavage of nanogel nanostructure within the endosomes by TEM.
This multi-functional DDS, combing with stimuli-triggered release potential, therapeutic agent and MRI contrast agent, is expected to be delivered as a versatile platform for on-demand releasing drugs to those acidic cellular compartments or disease microenvironments, such as diabetes, and biomedical diagnosis.

Poly(2-oxazoline)s (POx) are an interesting, yet less well-known class of polymers although they are thermo-responsive [1], non-toxic and possess similar stealth properties as PEG [2]. Thus, they represent highly promising materials for the development of intelligent drug delivery devices in various kinds of compositions, such as linear, block or comb-like macromolecules, and hydrogels. Thereby, the living cationic ring-opening polymerization (CROP) mechanism allows a straightforward design of the polymer properties by copolymerization as well as the attachment of cell targeting ligands or labels.
A range of thermo-responsive comb and graft copolymers are accessible by end-capping the living oxazolinium species from the CROP of 2-ethyl-2-oxazoline (EtOx) and reversible addition fragmentation chain transfer (RAFT) polymerization of the obtained macromonomers. On the one hand, this allows insights into the lower critical solution temperature (LCST) behavior of polymers that exist as macromolecular bottle brushes in aqueous solution [3]. On the other hand, the LCST properties can be brought into the physiological range by copolymerization with methacrylate-based monomers, such as methyl methacrylate and methacrylic acid [4,5]. Due to the introduced carboxylic acid moieties, the latter graft polymers are responsive not only to temperature but in to the pH value as well. In addition, the advanced polymeric architectures have been functionalized with cell-targeting sugars selectively at the end of the side chains [6].
Another way to introduce thermo-responsiveness into POx is the variation of the side group of linear polymers by the co-polymerization of functional 2-oxazolines. The introduction of primary amine groups using a statistical co-polymerization results in a system whose LCST depends on the pH value. The gelation of these phase separated polymer solutions by cross-linking of the amine moieties leads to hydrogels with a distinct microstructure. The resulting cationic networks can be used to selectively bind and release genetic material for the purpose of purification or detection in microarrays and DNA chips.[7]
1. C. Weber, R. Hoogenboom, U. S. Schubert, Prog. Polym. Sci. 2012, 37, 686-714.
2. K. Knop, R. Hoogenboom, D. Fischer, U. S. Schubert, Angew. Chem. Int. Ed. 2010, 49, 6288-6308.
3. C. Weber, S. Rogers, A. Vollrath, S. Hoeppener, T. Rudolph, N. Fritz, R. Hoogenboom, U. S. Schubert, J. Polym. Sci.; Part A: Polym. Chem. 2013, 51, 139-148.
4. C. Weber, C. R. Becer, R. Hoogenboom, U. S. Schubert, Macromolecules 2009, 42, 2965-2971.
5. C. Weber, C. R. Becer, W. Guenther, R. Hoogenboom, U. S. Schubert, Macromolecules 2010, 43, 160-167.
6. C. Weber, J. A. Czaplewska, A. Baumgaertel, E. Altuntas, M. Gottschaldt, R. Hoogenboom, U. S. Schubert, Macromolecules 2012, 45, 46-55.
7. M. Hartlieb, D. Pretzel, K. Kempe, C. Fritzsche, R. M. Paulus, M. Gottschaldt, U. S. Schubert, Soft Matter 2013, 9, 4693-4704.

The dynamic control over materials shape plays a key role in the complex biological environment and has attracted considerable attention in science, engineering, and medicine. We report on a dynamic volume transitions exhibited by ultrathin hollow hydrogel microcontainers of cubical shapes, also called hydrogel capsules. These cubical capsules were produced as poly(methacrylic acid)-based hydrogel (PMAA) replicas of cubical sacrificial templates and obtained from chemically cross-linked multilayers of hydrogen-bonded ultrathin films. We found that pH-induced volume transitions in those systems were strongly influenced by capsule shell thickness, composition, and crosslink density. While one-component (PMAA)20 cubical capsules turned into bulged spherical-like structures when transitioned from acidic to basic pH values, more rigid two component PMAA-poly(vinylpyrrolidone) capsules retained their cubical shape and increased in size instead. This pH-triggered size and shape changes were completely reversible. The drastic difference in pH-triggered shape responses was rationalized through the difference in hydrogel rigidity expressed as the ratio of the polymer contour length between the neighboring cross-links to persistence polymer length. Those ratios of 22.7 and 2 for (PMAA) and (PVPON-PMAA) systems, respectively, suggested that dual-component system is more rigid and therefore expand uniformly in all directions upon pH-triggered swelling. We believe that these results provide new prospects for developing polymeric materials with predictable shape and size-changing properties for controlled drug delivery, cellular uptake, and in pH-regulating transport behavior in microfluidic devices.

The nanostructure and nanomechanical properties of aggrecan monomers extracted and purified from human articular cartilage from donors of different ages have recently been visualized and quantified via atomic force microscopy (AFM)-based imaging, force spectroscopy, and high bandwidth nano-rheology. AFM imaging enabled direct comparison of full length monomers at different ages. The demonstrably shorter glycosaminoglycan (GAG) chains observed in adult full length aggrecan monomers, compared to newborn monomers, also reflects markedly altered biosynthesis with age. Direct visualization of aggrecan subjected to chondroitinase and/or keratanase treatment revealed conformational properties of aggrecan monomers associated with chondroitin sulfate and keratan sulfate GAG chains. Furthermore, compressive stiffness of chemically end-attached layers of adult and newborn aggrecan was measured in various ionic strength aqueous solutions, suggesting the importance of both electrostatic and non-electrostatic interactions in nanomechanical stiffness. These results provide molecular-level evidence of the effects of age on the conformational and nanomechanical properties of aggrecan, with direct implications for the effects of aggrecan nanostructure on the age-dependence of gel-like properties of cartilage tissue. Poroelastic interactions of interstitial fluid flow with cartilage extracellular matrix, in particular aggrecan proteoglycans, has been hypothesized to be the underlying mechanism in many critical functions of hydrated soft tissues such as transport, energy dissipation, and self-stiffening. However, the quantification and detailed mechanism of molecular level fluid-solid interactions in these systems is largely unknown. We recently studied brush layers of aggrecan from these same different aged human donors, and utilizing a new high frequency atomic force microscope (AFM)-based rheology system quantified the dynamic mechanical behavior of the solid-fluid interactions in the 1Hz to 10 kHz frequency range. Most dramatically, the magnitude and phase angle of the dynamic stiffness showed frequency-dependent trends remarkably similar to those of intact native cartilage tissue. For the first time, we were able to estimate the hydraulic permeability of aggrecan networks. These results confirm that aggrecan is the key molecule in determining the fluid-flow-dependent properties of cartilaginous tissues.

Connective tissues such as tendon, ligament, fascia, and cartilage require the presence of large, organized collagen fiber bundles to achieve sufficient load bearing capacity in tension and shear. This assembly of collagen fibers can also result in high degrees of mechanical anisotropy. While such structure and properties are routinely achieved in natural tissues, they are often lacking in tissue-engineered implants. How such structures are formed developmentally is not fully understood. However, their formation coincides with the transition of stem cells from a rounded shape and undifferentiated state to an elongated shape associated with a fibrous phenotype. It has been known for more than three decades that fibroblastic cells exert traction forces that cause mechanical remodeling of collagenous matrices. We hypothesized that these cellular traction forces could be directed to control collagen matrix assembly through the manipulation of mechanical boundary conditions imposed on tissue-engineered implants during extended cell culture.
We explored this hypothesis in experiments aimed at tissue engineering of two types of fibrocartilage, the annulus fibrosus and the meniscus. In both tissues, large collagen fiber bundles are oriented circumferentially in the plane orthogonal to the direction of loading. To guide the formation of such fibers in engineered tissues, fibrochondrocytes from these tissues were seeded into collagen gels in concentrations ranging from 1 to 20 mg/ml. Collagen gels were molded into shapes that were appropriate for the target tissues - a flat ring for the annulus fibrosus and a semi-lunar wedge with a triangular cross section for the meniscus. For both shapes, cellular collagen gels were cultured for up to 4 weeks under varying static mechanical constraints. Controls for both group were unconstrained and allowed to contract freely, while a rigid, impermeable cylinder was placed at the inner edge of the annulus fibrosus constructs and the meniscus constructs were clamped at the edges (i.e. “horns”) to direct contraction.
For both cell types, mechanically unconstrained gels contracted dramatically, shrinking to <10% of their original volumes. This contraction was associated with the formation of small (1-3 um), unorganized fiber bundles. The compressive and tensile moduli of these samples increased slightly, but the resulting tissue was isotropic. The mechanically constrained implants produced networks of circumferentially organized bundles of fibers similar in size to those in the native tissues (10-20 um). The tensile modulus of constrained gels increased up to 10-fold over 4 weeks and exhibited significant anisotropy, being 3-4 fold higher in the circumferential direction compared to radial direction.
These studies demonstrate the importance of cellular traction forces on the development of collagen organization in fibrous tissues, and point to new methods to control this process in tissue engineering.

Two primary paradigms have been used to understand and explain the functional properties of cartilage, such as its load bearing and lubricating ability. One family of phenomenological models describe cartilage as a charged, poroelastic continuum (like a charged clay) with a charged elastic network phase that can bear mechanical load, and an interpenetrating ionic fluid phase that can develop a hydrostatic pore pressure. Historically, these models have not distinguished among the soft molecular constituents comprising cartilage&’s elastic network, which includes collagen, proteoglycans, and polysaccharides. Another approach tries to explain functional material properties of these tissues as arising from polymeric interactions between and among the different molecular constituents within the tissue. This approach treats the tissue effectively as a complex molecular composite containing highly charged polysaccharide microgels trapped within a fine collagen meshwork. We have been developing a multi-scale experimental and theoretical framework to explain key material properties of cartilage by studying their constituents and interactions among them at a variety of length and time scales. We use this approach to address important biological questions, such as, Why doesn&’t cartilage collapse like other polyelectrolytes, in the presence of the high calcium ion concentrations present in joints, particularly near the bone-cartilage interface? Why is the diffusivity of aggrecan so much larger than that measured in free solution? How do aggrecans self-aggregate and what is the functional significance of the microgel structures they form? Is there any evidence of cross-linking between the collagen network and the polysaccharides they entrap? One novel application we plan to focus on here is the use of various complementary non-invasive magnetic resonance imaging (MRI) methods to characterize different components and compartments within cartilage and the different water environments associated with each one, in an attempt to provide a comprehensive picture of the mechanical/chemical state of cartilage.

Regenerative medicine is an emerging interdisciplinary field. Of the three essential elements for tissue engineering (i.e., stem cells, differentiation signals and scaffolds), the recent progress in the development of cell sources and in the identification of essential signals has been remarkable. With regard to scaffolds, hydrogels are promising materials because their structural compositions are similar to those of the soft tissues in the human body. Certain hydrogels can be injected in solution and transformed into the gel state with the required shape, which is an indispensable prerequisite for minimally invasive surgery. However, no injectable hydrogel has reached a practical stage as structural materials, mainly due to the fact that all the conventional hydrogels inevitably “swell” under physiological conditions (i.e., in an aqueous environment at 37°C), which drastically spoils their mechanical properties. Moreover, their morphological changes induce slippage from the installation site, and the swelling pressure damages the surrounding tissues. Here we report the design and fabrication of a “non-swellable” hydrogel that can be injected as aqueous solutions and retain its initial shape under physiological conditions. This novel hydrogel, whose swelling is suppressed, can endure a compressive stress of up to 60 MPa and can be stretched more than seven-fold with no hysteresis. In stark contrast, conventional hydrogels exhibit highly reduced mechanical strength when swollen in an aqueous environment. Our results demonstrate that the swelling suppression of hydrogels may help maintain their initial shape and retain their mechanical properties under physiological conditions. The hydrogel reported herein may constitute scaffolds for cartilage, which is exposed to a high mechanical overload (up to 20 MPa). This methodology will be a versatile strategy for the design of hydrogels as structural materials used in various disciplines and may possibly advance conventional hydrogels to the practical application stage.

Various forms of “bioprinter” allow cells and scaffold material to be built layer-by-layer into 3D structures. Alginate, cross-linked by calcium ions, is widely used for this purpose but this and most synthetic gels are weak. In contrast, soft tissues such as cartilage, skin and arterial wall are strong and tough. An ideal gel for 3D tissue engineering would be tough enough to be surgically sutured, would be cytocompatible before and after curing, would have transport properties good enough to allow nutrients and proteins to reach cells and would provide anchorage sites for cells.
The double-network gels developed by Gong et al. have shown that tough synthetic gels can be made but the process does not lend itself to 3D fabrication. We have explored a number of combinations of covalent gels with biopolymer electrolytes such as alginate, gellan and carageenan. In terms of fracture mechanics, the great toughness of these composite gels can be attributed to the energy absorbed by slippage of the calcium-crossliked biopolymer at the tip of any crack in the gel while the elastic modulus is maintained by the covalent network. These materials can be extruded to form designed 3D structures with internal channels for nutrient flow, property gradients and functional segments such as internal electrodes.

Heart failure post-myocardial infarction (MI) is the leading cause of cardiovascular related deaths in the United States. There is pressing need to develop new treatment approaches. An injectable decellularized cardiac extracellular matrix (ECM)-based hydrogel, termed myocardial matrix, has shown promise at preventing post-MI heart failure in rat and porcine MI models. However, this ECM-based material has a limited range of properties thus limiting its potential applications. Herein we develop a new class of tissue specific biomaterials for cardiac tissue engineering by synthesizing myocardial matrix-polyethylene glycol (PEG) hybrid hydrogels. We studied and compared two different methods to crosslink PEG to the protein network; amidation and radical crosslinking. A star-PEG-NHS polymer at different concentrations was mixed with myocardial matrix for the amidated system. Two different multi-armed PEG-acrylates at different concentrations were mixed with vinyl functionalized myocardial matrix for the photo-initiated radical system. The hybrid gels were swelled in water and then ethanol to remove any material not conjugated to the network and the infrared spectrum recorded. The myocardial matrix had no strong peaks near 1150 cm-1, while all of the myocardial matrix-PEG hybrids have a strong peaks at 1150 cm-1 indicative of a C-O stretch present from PEG. Additionally the peaks from 1250-1750 cm-1 in all hybrid spectra decrease in intensity relative to the C-O peak with increasing PEG concentration. PEG incorporation was also confirmed by gel electrophoresis. The stiffness of amidated system with the highest amount of PEG was six times higher than the myocardial matrix alone, while stiffness of the radical hybrid was 140 times stiffer by parallel plate rheometry. Scanning electron micrscopy demonstrated that the hybrids maintained the nanofibrous structure of self assembled myocardial matrix (fiber diameter = 85 nm) and that fiber diameter could tuned based on the method and amount of PEG incorporation (fiber diameter = 80-210 nm). The hybrids also were enzymatically degraded 2-3 times slower than the myocardial matrix based on quantification of soluble amines with ninhydrin assay allowing for tunable enzymatic degradation. Amidated hybrids allow for cells to migrate easily through the material as assessed by calcein AM labeled cells and still renders the material injectable similar to the unmodified myocardial matrix. The photo-initiated radical system has rapid gelation upon irradiation, which allow for cells to be encapsulated. The encapsulation process results in high cell viability (>95%) and the alamar blue assay showed that the cells remain metabolically active 5 days after encapsulation. PEG incorporation into myocardial matrix protein network results in tissue specific hydrogels with tunable properties, which will expand the scope of application of these materials for cardiac tissue engineering.

We have used reactive inkjet printing to built thick layers of self-assembled gels from anionic and cationic polyelectrolytes. The diffusion from these gels of small molecule dyes, dextran polymers and albumin have been measured.
Covalently cross-linked synthetic gels are often viewed as a network. This implies that molecules smaller than the mesh size will diffuse easily through the gel but larger molecules will show a molecular weight cut-off above which the molecule is trapped. Since many biological tissues have a gel component, this does raise a question of whether that would also prevent transport of large proteins through tissue.
In the case of polyelectrolyte gels, the cross-linking is via ionic bonding which can re-equilibrate around the diffusing species. This can-of-worms model will allow molecules of any size to move through the gel. Our results show that the diffusion coefficients of fluorescein and dextran are about 1/100 that of water in the gels, while albumin has a diffusion coefficient about 1/1000 that of water. Results on the electrically-driven release of dyes and albumin from these gels will also be presented.

Hydrogels show immense potential in many areas including biosensing, drug delivery, and tissue engineering and regeneration applications due to their mechanical properties, wicking ability, and structure. There is also growing interest in integrating additional characteristics into hydrogels to expand their functional roles. In the context of neural regeneration, it is desirable to have hydrogels not only support neuron adhesion and neurite extension, but also capable of neural protection against hostile pathological surroundings. Herein we report a new system that bears the aforementioned features.
Hydrogels were prepared using a simple and novel epoxy-amine composition, which can proceed in an aqueous solution without additional catalysts or additives. Further, through variance of temperature, reaction time, and composition we are able to tune their properties such as mechanical properties, pore size, and swelling ratio for subsequent applications. The epoxy-amine chemistry introduces chemical groups that can be protonated at physiological conditions, thus rendering a cationic nature to the hydrogels to promote cell adhesion and potentially allow for delivery of growth factors via electrostatic binding effects. Another interesting feature of our hydrogel is the presence of a particulate microstructure within the macroporous network formed as a result of temperature-induced phase separation during hydrogel synthesis. Such micron-sized particles can potentially serve as reservoirs to hold and deliver therapeutics locally to increase cell survivability.
The morphology of the hydrogels was characterized with scanning electron microscopy, showing a highly interconnected macroporous, particulate-bearing network. The porous microstructure of the hydrated gels was also revealed with confocal microscopy by labeling the hydrophobic particulate domains with Nile Red dye molecules. Rheological studies were performed to characterize the mechanical properties of the hydrogels. Swelling ratio measurements were performed in phosphate buffered saline and monitored for gravimetric and volumetric changes, the results of which suggest a macroporous network. Preliminary studies of hydrogen peroxide induced degradation illustrate not only the oxidative biodegradability of the hydrogel but also the increase in the pore size and decrease in mechanical properties of the scaffold upon degradation. A direct contact assay using NIH 3T3 fibroblasts did not show signs of cytotoxicity after 24 hours. The applicability of the hydrogels as neural scaffolds was investigated with chick embryo derived cortical neurons, and calcein AM staining results showed that neurons were able to attach and extend neurites after one day of culture. Altogether, this novel multifunctional and biocompatible hydrogel system provides a new platform to engineer more effective solutions for neural repair and regeneration.

Poly(vinyl alcohol) (PVA) is a well-respected biomaterial and forms highly hydrated hydrogels. It has been used in a number of applications, such as tissue bulking and nerve-guides, but is not intrinsically biodegradable, nor substantially mucoadhesive. These features can be built in to the molecule through complex co-polymerizations, but here we describe a simpler route involving modification of existing off-the-shelf materials.
Biodegradable hydrogels based on PVA modified with thiol groups (TPVA) were prepared and characterized. The TPVA was synthesized by an esterification reaction of PVA with 3-mercaptopropionic acid and characterized by 1H NMR. The TPVA produced contained pendant chains with ester bonds linking the thiol groups to the PVA backbone. Further, hydrogels were synthesized from this TPVA in a reaction between the TPVA and acrylate derivatives of poly(ethylene glycol) using Michael-type addition. The gelation reaction between the TPVA and PEG-acrylate proceeded under physiological conditions in aqueous environment without radical initiators or irradiation. The kinetics of gelation, including gelation time and dynamic modulus, were determined by rheology. The properties of the final hydrogels and cure characteristics were investigated as a function of pH, polymer concentration, molecular weight, degree of PVA and PEG chemical modifications and their ratio in the composition. The gelation time varied from seconds to 30 minutes and the equilibrium elastic modulus (G&’) was in the range 500 Pa to 10 kPa.
The hydrogels were rendered degradable by the presence of the ester groups, which are easily hydrolysable and do not require the presence of enzymes for degradation to occur. In addition, the thiol-functional groups impart mucoadhesive properties to the PVA hydrogels, as has been reported elsewhere. The level of mucoadhesion was controlled by the amount of free thiol functionalities remaining uncrosslinked after the hydrogel formation reaction between the TPVA and PEG-acrylate molecules.
The degradability and swellability of these PVA-PEG hydrogels was tested in 1xPBS under ambient conditions. The hydrogels at 3 wt % polymer solids started losing mechanical integrity after 18 days and completely dissolved after 35 days. In addition, a specialized peel test was developed to measure the mucoadhesive properties of the hydrated TPVA hydrogel.

In this work, we reported the first example that the supramolecular hydrogel formed by small molecule show strain hardening. Enzyme-triggered self-assembly could modulate the strain hardening through changing the amount of enzyme, which change the pathway of self-assembly and result in different morphology of hydrogel. The step strain experiment showed that the supramolecular hydrogel could increase the relaxation modulus six times at the short time scale, TEM images reveal that the strain hardening caused by the unique semi-flexible filament and rod-like structure.

Electro-active actuators composed of ionic polymers and ionic liquids (ILs) have been extensively studied for biomimetic technologies such as soft robotics and artificial muscles. Major challenges in achieving practically viable actuators are the development of low driving voltage, fast response time and durable operation in air, which are yet endeavoring for many proposed systems. Herein, we are motivated to solve these issues by employing ILs-containing nano-structured block copolymers as an ionic polymer layer in the actuators. We prepared diverse ILs-containing block copolymers and a range of heterocyclic diazole-based ILs. It has been revealed that the type of cations in ILs impacts the electromechanical deformation of the actuators. Particularly, the used of sulfonated block copolymer possessing nanoscale ionic channels resulted in greatly improved switching time, in comparison to the state-of-the-art PVdF-based actuators, upon building up less tortuous ion conduction pathway. In addition, the new actuators developed in the present study displayed the best performance exceeding those of other ionic polymer actuators reported to date under sub-1V operation conditions. In-situ SAXS experiments were carried out to underpin the actuation mechanism of the new actuator and the key to success stemmed from the evolution of the unique nanostructure of the electrolyte layer with dimensional gradients beneath the cathode during actuation, which promoted the bending motion of the actuators.

Facile strategy to the synthesis of monodispersed microgels with optical properties has been developed. The cheap and commercially available dye of Bordeaux R. was selected as the optical code. The rationally selected co-monomers and dye molecules can be copolymerized into one-pot via free radical precipitation polymerization in an aqueous solution. With a rational design, the dye-embedded microgels are able to sense the environmental glucose concentration changes at physiological pH, and thus convert the chemical changes into optical signal changes. The dye-composited microgels demonstrated good performance in stability, as well as high glucose sensitivity, which is promising for continuous glucose detection.

Design of alternative, energy-efficient processes for recovery of butanol and ethanol from dilute (15 to 50 g/L) fermentation effluents is vital to the biofuels industry, especially for cellulose-derived systems that produce low concentrations of product. Our work deals with gel stripping, a column-based absorption process that presents advantages compared to both extractive fermentation processes and pervaporation. The raw fermentation product is passed through a vertical column containing a selective polymer gel material, which absorbs the alcohol component and allows excess water and other waste components to drain from the system. The concentrated alcohol is recovered by vacuum distillation from the gel without the need to distill large quantities of water. Without requiring sophisticated synthetic techniques or processing equipment, gel stripping provides unparalleled separation efficiency, while the flexibility in gel material design equips the biofuels industry with methods to rapidly tune material performance to meet the evolving needs of recovery processes.
The major challenge in gel stripping is to design an absorbant gel material that is both reasonably selective for the alcohol and able to swell to a high degree in dilute alcohol-water mixtures. This materials design problem is non-trivial because the entropy of mixing of alcohol and water is high enough to discourage the alcohol from entering the gel, even when the gel swells highly in pure alcohol. To accelerate materials optimization, an innovative high-throughput screening approach has been applied to polymeric materials for gel stripping. Gels based upon random copolymers of hydrophobic and hydrophilic functional monomers are studied as a model system. A combinatorial approach is taken to screen a matrix of copolymer gels having orthogonal gradients in crosslinker concentration and copolymer composition. Using a combination of swelling in pure solvents (water or alcohol) and solvent mixtures (water + alcohol), the selectivity and distribution coefficients of alcohol in the gels can be obtained.
HPLC analysis can be used to experimentally measure selectivity and distribution coefficients of alcohols in the gels, but the analysis is labor-intensive. Thus, a combined experimental/theoretical approach is developed, which allows prediction of selectivities from the equilibrium swelling data in pure solvents, which are rapidly acquired. A four-component (two monomer units, two solvents) extension of Flory-Rehner theory permits near-quantitative predictions of selectivity in random copolymer networks in water/alcohol mixtures.
Using high-performing gel materials identified by the screening approach, the gel stripping process has been applied to ethanol and butanol stripping processes with high recovery rates.

Biodegradable polymers have attracted widespread interest for both medical and pharmaceutical applications. Specifically, aliphatic poly(carbonate)s are an important class of biodegradable polymers with applications in tissue engineering, medical devices and drug delivery systems. Herein, we present the synthesis of various poly(1,2-glycerol carbonate)s via an alternating copolymerization of carbon dioxide with glycidyl ethers. The pre- and post-polymerization modifications of the pendant side chains of the polymer allow a facile and efficient access to a class of functional poly(1,2-glycerol carbonate)s. Hence, polymer properties can be tuned, including hydrophilicity and hydrophobicity, membrane permeability, bioadhesive ability, biocompatibility and biodegradability.

The sol-gel characteristics of styrene-isoprene-styrene block copolymer (SIS) solution were investigated by selecting solvents with different block-selectivity using mixed different solvents. Toluene is a nonselective good solvent for both styrene and isoprene molecular blocks in SIS, while heptane is a good solvent just for isoprene (isoprene-selective), and N, N-dimethylformamide (DMF) is a poorer solvent for the isoprene block than the styrene block (styrene-selective), respectively. By mixing heptane into toluene at various ratios to change the block selectivity from non-selective to isoprene -selective, the sol-gel transition of the SIS solution was observed. Such sol-gel characteristics were also observed by mixing DMF with toluene at various ratios, while the block selectivity was changed from non-selective to styrene-selective. To evaluate the effects of the solvent selectivity on the mechanical characteristics of SIS solution, the viscoelastic properties of the SIS solution were examined by the dynamical mechanical analysis (DMA) with the strain-controlled rheometer. The solution prepared with pure toluene presented almost complete liquid sol characteristics. It was found that, as the ratio of the selective solvent in toluene increased, the dynamic modulus of the solution also increased gradually. In more detail, when heptane and toluene were mixed at 90:10, the resulting solution became turbid in a more solid gel state around the concentration of 10wt%. When DMF and toluene were mixed at 40:60, the resulting solution also became turbid in a more solid gel state around the concentration of 15wt%. It was considered that in the isoprene-selective solvent (heptane), SIS was tethered at both ends of the styrene blocks, establishing loop and bridge molecular conformations. It was also considered that in the styrene-selective solvent (DMF), SIS was tethered at the isoprene block forming physical networks at higher polymer concentrations, which was comparable to the solution of SI diblock. This was confirmed by the structural analyses of the SIS solution conducted by the light scattering method. From the results, it was found that the sol-gel transitions could be effectively controlled by changing the selectivity of solvents. The experimental perception could be well applied to the control of the spinnability of SIS, which was strongly related to the viscoelastic studies of the SIS solution.

The use of colloids with anisotropic shape and properties enable the assembly of advanced materials otherwise not attainable by microfabrication. In this study, we present a convienent method using common microfabrication tools for generating a diverse array of microparticles with well-defined and tunable shapes, sizes, electromagnetic properties for passive and active assembly. Projection photolithography onto SU-8 photoresist enabled the production of large-aspect ratio particles such as cubes, cuboids, cylinders, hexagonal prisms, and parallelepipeds. We characterized fabricated particles with energy-dispersive X-ray spectroscopy, scanning electron microscopy, and optical microscopy. Larger particles (e.g., 1,000 µm3) were released from the silicon substrate via gentle sheer forces, whereas smaller particles (e.g., 8 µm3) were released by a water-soluable sacrificial layer underneath the SU-8. Suspending the released microparticles in surfactant and water (or other suitable solvents such as deuterium oxide) provided amenable conditions for their self-assembly. Some anisotropically-shaped particles were prepared for dehydration assembly by placing a suspension of particles inside a hydrophobic ring on a flat surface for controlled evaporation. Other particles were prepared for field-directed assembly by decorating particles with metallic patches in precise locations along the particle surface (e.g., top, side or multiple sides) using electron beam metal evaporation. This enabled orientational control of the particles during assembly in dielectric and magnetic fields. Particles fabricated for dielectrophoretic and magnetophoretic assembly were coated with patches of gold and cobalt, respectively. By tuning the shape, size, and location of metallic patches as well as the strength and frequency of the applied field, we generated a broad range of architectures in directed-fields including small ordered clusters, chains, and lattices. Additionally, fluorescent stains (e.g., Nile red) were mixed into the photoresist resin to enhance the visualization of the particle orientation the during assembly process. These findings to be presented have the potential to catalyze future research in the field of anisotropic patchy particle assembly for use in applications such as micromirrors, biosensors, and photonic crystals.

Cartilage is a connective tissue located at the end of bones. It is also found in numerous parts of the body such as the nose, ear, epiglottis, shoulder blade, the ribs and the diarthroidal joints (elbow and knees). Cartilage is a complex biological tissue that exhibits gel-like behavior. Its major biological function is providing compressive resistance to external loading and nearly frictionless lubrication of joints.
There is a decent body of knowledge in regards to the biochemistry that underlies the biological and biochemical properties of the various components of cartilage tissue. However, cartilage also performs many biomechanical roles and, therefore, it is essential to understand the physical and chemical interactions between the components of the cartilage matrix. The objective of our work is to develop an appropriate model system, which possesses cartilage-like biomechanical properties. We would also like to quantify important physical parameters relevant to the functional properties of cartilage. In this study cartilage extracellular matrix is modeled by a biomimetic system. We demonstrate that poly(vinyl alcohol) (PVA) hydrogels are robust biomaterials exhibiting mechanical and swelling properties similar to that of cartilage. A comparison is made between the macroscopic behavior of PVA gels and literature data reported for cartilage.

Due to a great number of potential applications in broad areas of material sciences, hydrogels have attracted increasing attention. Hydrogels are classified into covalent and non-covalent (supramolecular) ones. Covalent hydrogels consist of covalently crosslinked 3D networks and can generally provide excellent mechanical properties. On the other hand, supramolecular hydrogels are composed of non-covalent 3D networks, which are readily available by simply mixing necessary components in water but are generally weak and not moldable into freestanding objects. Quite recently, we developed a mechanically tough supramolecular hydrogel using a molecular glue and clay nanosheets (Nature 2010, 463, 339-343 / Nature Commun. in press). This hydrogel is characterized by its ultralow-content organic component (0.2 wt%) that usually leads to extremely poor mechanical properties. Our key molecular design strategy was to utilize a water-soluble telechelic dendron that strongly adheres to clay nanosheets by its guanidinium ion pendants, where the resultant non-covalent 3D hydrogel network is mechanically tough and well developed in water up to a macroscopic length scale. This work initiated a paradigm shift in the development of hydrogels. However, for large-scale practical applications, there exists an essential problem caused by a poor synthetic availability of the dendritic molecular glue. Herein we report novel water-soluble molecular glues based on multiblock copolymers readily available by polycondensation. The multiblock copolymers consist of an alternating sequence of a polyethylene glycol block and an adhesive block with main-chain guanidinium ion units, and tightly connect clay nanosheets together for the generation of a 3D network structure in water. In the present paper, we report details of the preparation and physical properties of such novel aquamaterials.

Hydrogen bonded multilayer thin films containing tannic acid (TA) and poly(vinyl alcohol) (PVA) were assembled under different pH conditions, and film growth and dissolution behavior was assessed through profilometry. Optimal film growth was achieved at pH 4.0, which contrasted with uncontrollable assembly at lower pH and lack of growth at higher pH. Changes in growth behavior due to variations in the molecular weight and degree of hydrolysis of PVA, as well as the concentration of the two components, were also investigated. High molecular weight PVA resulted in thicker films than low molecular weight PVA in two cases: fully hydrolyzed PVA at a concentration of 1.0 mg/mL and partially hydrolyzed PVA at a concentration of 0.1 mg/mL. In addition, the dynamic adsorption and desorption behavior of these films was investigated using QCM-D. The pH stability of the PVA/TA films was higher than other previously investigated PVA based multilayer systems, which is consistent with the high pKa value of TA of 8.5. This increased pH stability, combined with the antioxidant, antimicrobial, antimutagenic, antitumor, and antibacterial properties of TA and the biocompatibility of PVA, makes the PVA/TA system attractive for biomedical applications.

Introducing heterogeneous functionality with precision in polymeric materials provides unprecedented control and means to evaluate various materials properties for technological advancements. While many efforts have focused on top-down lithographic processes and rigid rod-coil block copolymers to make nanostructured heterojunctions, there is a lack of systematic studies on the use of small molecule mesogens in copolymers to study electron transfer in thin-films and bulk. We study the self-assembly of semiconducting block copolymer liquid crystals to obtain highly ordered nanostructured semiconductors. Intrachain electron transfer is studied by photophysical measurement. The latest results will be discussed in the presentation.

Solar energy has recently attracted great interest as a sustainable and environmental green energy source. The self-assembly of bio-supramolecules into nanostructures is an attractive route to fabricate biomimetric photosynthesis systems. In this work, peptide Fmoc-LLL which had strong π-π stacking and self-assembled helix-structured nanofibres was synthesized to form conductive hydrogels.1 After incorporated with hydrophobic porphyrin derivative, the self-assembly of porphyrin occurred on the surface of the Fmoc-LLL nanofibres by hydrophobic interactions and hydrogen bonding, which endowed the gels with light-harvesting properties and enhanced the electro-conductivity. Simple devices containing the Fmoc-LLL/porphyrin hybrid gel-phase systems were shown to have knowable electro-chemical properties. We are currently working to develop systems which integrate hydrogenase photo-catalytic system for visible light-driven effective hydrogen regeneration.
[1] H. Xu, A.K. Das, M. Horie, M.S. Shaik, A.M. Smith, Y. Luo, X. Lu, R. Collins, S.Y. Liem, S. Song, P.L.A. Popelier, M.L. Turner, P. Xiao, I.A. Kinloch, R.V. Ulijn, Nanoscale, 2010, 2, 960-966.

Covalent bonds with the ability to reach an equilibrium state between combination and dissociation under certain conditions have been studied, and systematic method for controlling the structures of compounds and polymers based on these reversible covalent bonds has been spotlighted as dynamic covalent chemistry. In the present study, reorganizable, self-healing, and mechanochromic dynamic covalent polymer gels were designed.
Alkoxyamine-based covalently networked polymers were designed with two notable functionalities, de-cross-linking by dynamic covalent exchange based on a radical crossover reaction and insertion of vinyl monomers into the cross-linkers. The variation of the network structures in these reactions was successfully evaluated by gel permeation chromatography, small-angle X-ray scattering, and rheological measurements.
Cross-linked polymers with exchangeable dynamic covalent bonds at room temperature were synthesized by polyaddition of diarylbibenzofuranone (DABBF)-tetraol and tolylene diisocyanate terminated polypropylene glycol. The self-healing property of the DABBF-containing cross-linked polymer gel was investigated under air at room temperature. The gel samples were prepared and cut with a razor blade to expose fresh surfaces. The fresh surfaces were brought together immediately in the absence of external force. The in-contact samples were kept at room temperature under air. After 24 h, self-healing of the contacted samples could be observed and the scars had almost disappeared. Even after manually stretching the sample, no destruction occurred. Tensile tests were also performed to quantitatively evaluate self-healing properties. A recovery of 98 % of the original elongation at breaking was possible over periods of 24 h.
Stimuli-responsive polymers which change color by mechanical stress were also synthesized and their mechanochromic behavior was investigated. Since the central C-C bond in DABBF has lower bond dissociation energy, DABBF can reversibly cleave to the corresponding radicals with blue color. We employed DABBF as a mechanochromic unit. DABBF-containing polyurethane films were prepared and their elongation-induced or freezing-induced mechanochromism was observed.

Biologically stimuli-responsive gels that undergo changes in volume in response to a target biomolecule, so-called biomolecule-responsive gels, are useful tools for fabricating molecular diagnostic systems and self-regulated DDS. We proposed a novel strategy to prepare biomolecule-responsive gels; our strategy uses biomolecular complexes as dynamic crosslinks that dissociate and associate in the presence and absence of a target biomolecule, respectively. On the basis of this strategy, we prepared various biomolecule-responsive gels that exhibit swelling/shrinking changes in response to a target biomolecule. Biomolecule-crosslinked gels that can swell in response to a target biomolecule have been designed by using saccharide-lectin complexes, antigen-antibody complexes and DNA duplexes as dynamic crosslinks in the gel networks. Biomolecule-imprinted gels that can shrink in the presence of a target biomolecule have been strategically prepared by biomolecular imprinting using various biomolecules as ligands for the target biomolecule. The responsive behavior of the biomolecule-crosslinked and biomolecule-imprinted gels is based on dissociation and association of biomolecular complexes as dynamic crosslinks. In addition, methods for preparing biomolecule-responsive gel particles and thin films that undergo changes in volume in response to a target biomolecule are also reported. Thus, biomolecule-responsive gels, particles and thin films have many potential applications as smart biomaterials for constructing self-regulated DDS and molecular diagnostic systems. This paper demonstrates that the utilization of molecular complexes as dynamic crosslinks is fascinating idea for the creation of biologically stimuli-responsive gels with molecular recognition abilities.

The biomedical potential of conventional chemically crosslinked hydrogels is often compromised by processing difficulties and by the potential toxic effects of residual unreacted species. To overcome these limitations, we are studying block polymers that undergo reversible sol-gel transitions under controlled temperature and pH conditions. RAFT polymerization was employed to synthesize a poly(N-isopropylacrylamide)-poly(N-isopropylacrylamide-co-acrylic acid)-poly(N,N-diethylacrylamide) triblock polymer. The triblock employs thermoresponsive side blocks and a dual temperature/pH-responsive middle block. NMR, GPC, and potentiometric titration were used to determine block lengths and composition of the middle block. Polymer phase behavior in dilute aqueous buffered solutions was investigated with temperature varying over the range 20-60 C, and pH varying between 2 and 8. Polymer aggregation and aggregate sizes were detected using UV spectroscopy and dynamic light scattering, respectively. The onset of gelation in concentrated solutions was studied by dynamic mechanical analysis.. At low temperatures (below 32 C), the polymer chains were soluble at all pH values. At elevated temperatures, the polymer phase separated from aqueous solution to form aggregates, which were swollen and highly viscoelastic (with comparable storage and loss moduli) at 10% polymer concentration and at pH 8.. Aggregates reverted to the sol state upon cooling. With some improvements, it is expected that tough physical gels, whose swelling is jointly pH- and temperature dependent, will result, and that their thermoreversibility will provide advantages in processing and shaping of devices that contain or are based on such materials.

It&’s of great importance to reduce CO2 emission from fire power plants to prevent global climate change. Aqueous solutions of amine is the most common CO2 absorbent used in industrial CO2-capture process. However, the huge energy consumption required in the amine regeneration process limit the use of the absorbent for the power plants. Energy consumption for regeneration of the porous solid adsorbent such as zeolites and metal organic frameworks is smaller than the aqueous amines. However, an additional gas-drying process is required to use the adsorbent, since water in the combustion gas compete with CO2 adsorption and/or liquefied water block up the pores.
In this study, we report that temperature responsive hydrogel films consisting of amine-containing microgel particle (GP) exhibit large capacity to absorb CO2 reversibly in water saturated environment. The CO2 absorption capacity was proportional to film thickness up to tens of micrometers while the dry film did not show any absorption. Temperature change between 30 °C and 75 °C induced phase transition of the GPs, causing a large pKa shift of amines copolymerized within the GPs, consequently CO2 was absorbed and desorbed reversibly at a high chemical stoichiometric efficiency. The high CO2 absorption capacity and repeatability was not diminished even in water-saturated environment. This study shows the potential of hydrated GP films to sequester CO2 at a low energy cost.

Physically crosslinked injectable hydrogels have versatile biomedical applications, especially in minimally invasive surgery. However, their low yield stress, rapid erosion rate, and brittleness render these hydrogels unstable in physiological environment when subject to long term use. Here, we demonstrate topological entanglement as an effective means to increase the mechanical tunability of a transient hydrogel network based on coiled-coil association. Chain extended artificial proteins are prepared via disulfide formation. The molecular weight and molecular weight distribution in such polycondensation can be controlled by changing the reaction conditions, such as protein concentration and the coupling chemistry. The experimental results agree with Jacobson-Stockmayer theory, which provides a theoretical basis to analyze the molecular weight distribution and the linear chain fractions. Owing to the reversible nature of disulfide bonds, the entanglement effect as well as the resulting mechanical enhancement can be switched on and off by redox stimuli. Upon preparing the hydrogel in a physically entangled state, the surface erosion rate is suppressed by a factor of 5.8 and the creep compliance is reduced by a factor of 7.2. The enhanced stability enables hydrogels to be used in an open system with sustained load. Moreover, entanglement leads to significantly enhanced toughness approximately of 65,000 J/m3 and extremely high extensibility up to 3,000% engineering strain. Chain entanglement also drastically reduces the relaxation time and prevents early mechanical failure. At large deformation, it is hypothesized that entanglement chains are aligned along the loading direction, a strain hardening effect resembling the strain-induced crystallization in synthetic polymers. It is noteworthy that the mechanical enhancement does not lead to a large increase in stiffness: only 1.5-fold increase in plateau modulus is observed. Therefore, these materials show promise for the preparation of tough yet soft tissue simulants by chain entanglement. The relaxation times and zero-shear viscosity of gels are examined using the “sticky reptation” theory to investigate the interaction between the coiled-coil association and topological entanglement. The number density of the coiled-coil domains is varied to study its effect on network modulus and relaxation behaviors. A constitutive model is established to capture the stress-stress behavior with finite element analysis. In conclusion, we anticipate that chain entanglement can be generalized to other network chemistries and provides an important means of tailoring network properties to meeting emerging demands for tissue-mimetic hydrogels in the biomedical arena.

Functional stimuli responsive systems, for example, spontaneous thermonastic folding and unfolding reversible movements of the Rhododendron plant are widely observed in nature. These bioinspired approaches could provide a means to enable low-power functional, adaptive and autonomous systems in engineering. Stimuli responsive hydrogels have received considerable technological attentions as intelligent materials and they can respond to a variety of stimuli such as heat, pH, light source, electric fields, magnetic fields, mechanical stress or ionic strengths. These materials have found widespread applicability in drug delivery, soft-robotics, surgery and sensors. Notably, cross-linked poly N-isopropylacrylamide acrylic acid (PNIPAM-AAc) based hydrogels have been widely studied because of their reversible stimuli responsive properties just below physiological temperatures. Here, we describe a simply programmable MEMS inspired lithographic approach to design stimuli responsive self-folding 3D functional structures using thin films of PNIPAM-AAc. Using experiments and computational models, we first characterize the properties of these films and rationalize stimuli responsive folding mechanisms. We also demonstrate proof-of-concept that this methodology can be utilized to structure a range of devices including hydrogel capsules for drug, polymeric grippers for robotics and surgery, and pH steered optoelectronic micro-mirror systems for code reading, imaging, motion detecting and precision machining.

It has been historically challenging to engineer synthetic, responsive polymers that reproduce the mechanical sensing and signal transduction of biological systems. Here we demonstrate a synthetic system that can, in response to applied mechanical load, elicit a visible, chemical signal that propagates over long ranges and complex trajectories. This mechanically triggered signaling system comprises discrete hydrogels capable of undergoing a self-oscillatory redox reaction. We elucidate the mechanism by which compression triggers a chemical signal that is manifest in both color change of the gel and, for sufficiently small gels, mechanical actuation via gel swelling. We also engineer systems in which signal propagation traverses complex trajectories without decay in signal amplitude. These findings qualitatively mimic aspects of mechanotransduction among biological cells, and also describe intriguing new gel systems that convert and convey information about metal ion redox state and mechanical deformation.

We will present our recent activities in developing and applying photosensitized polymeric vesicles (polymersomes) that rupture under optical excitation [1, 2]. This special class of polymersomes [3, 4] enabled photon-triggered intracellular delivery at the single cell level, exhibiting ultra-fast payload distribution in the cell cytosol within 50 msec. This value is approximately higher by approximately two orders of magnitude than similar methods [5-7]. The polymersomes were formed from the block copolymer PEG17-bl-PPS30 [3]. Ethyl eosin, a photosensitizer that undergoes oxidation under illumination, was associated with the polymersome membrane via hydrophobic interactions.
Short light exposures lead to the re-organization of the polymersomes into smaller diameter vesicles, while extended illumination lead to complete polymersome destabilization, and micelle formation. The underlying light-vesicle interactions, referred to as vesicle photonics [2], were explored at the single particle level. At this level, the payload release and vesicle destabilization kinetics were measured, revealing that payload release takes place within seconds of illumination and in an explosive burst. At the single particle level, the generation rate of reactive oxygen species, particle size and osmotic pressure gradient across the polymersome membrane were also investigated in relation to the temporal delivery profile. Additionally, alternative photosensitizing chromophores were explored, as well as the interactions between photosensitized polymersomes under illumination.
As an example in quantitative cell biology, the polymersomes were delivered to antigen presenting cells and internalized through phagocytosis. Subsequent to internalization, the polymersomes resided in the endosomal compartment and upon illumination; the polymersomes locally release their payload first within the endosomes, and subsequently to the cytoplasm. With this mechanism, we delivered peptides in single cells and measured the peptide processing kinetics with high temporal resolution.
References
[1] A. E. Vasdekis*, E. A. Scott*, C. P. O&’Neil, D. Psaltis, J. A. Hubbell, ACS Nano 6, 7850 (2012).
[2] A. E. Vasdekis, E. A. Scott, S. R. Roke, J. A. Hubbell, D. Psaltis, Annual Reviews of Materials Research 43, to appear in July (2013).
[3] A. Napoli, et al., Nature Materials 3, 183 (2004).
[4] D. E. Discher, and A. Eisenberg, Science 297, 967 (2002).
[5] A. Prokop, Intracellular Delivery Fundamentals and Applications (2011).
[6] R. Palankar et al. Small, 5, 2168 (2009).
[7] K. A. D. Gregersen et al. ACS Nano 4, 7603 (2010).

In-the-field protection from of chemical warfare agents (CWAs) such as VX, sarin, or sulfur mustard is a challenging and important goal of the Second Skin concept. Our unique approach is to destroy these extremely toxic agents through the use of reactive catalytic compounds embedded in a reactive thin protective layer. This protective layer mimics living skin in that upon CWA challenge, it actively reacts with the agents, neutralizes the threat and then self-exfoliates, removing the contaminated layer and exposing fresh protective under-layers. We have expertise in network polymer systems (gels, polymer brushes and nanoparticles) that can be triggered to degrade and release upon appropriate chemical signaling events.[1,2] These network systems can be loaded with appropriate catalytic compounds and the byproduct of the destruction of the CWA will auto-catalyze the degradation of the network. These systems are selective, sensitive and automated, requiring no secondary sensing or external triggering to activate. The chemistries lend themselves to additional function, such as release of secondary compounds that may be used to alert the user of contamination or shutdown and block underlying layers. This talk will disclose the chemical structures and materials that have successfully displayed a triggered response.
REFERENCES:
(1) Jhaveri, S. B.; Carter, K. R. "Triggered decomposition of polymeric nanoparticles"; Macromolecules 2007, 40, 7874-7877.
(2) Koylu, D.; Carter, K. R. "Stimuli-Responsive Surfaces Utilizing Cleavable Polymer Brush Layers"; Macromolecules 2009, 42, 8655-8660.

Ultrathin polyelectrolyte hydrogels have shown considerable promise in controlled drug release, cellular, protein, or bacterial adhesion, ink-jet printing, and sensing, which makes structural information about such films is highly relevant. We report on tuning pH-induced swelling of ultrathin multilayer hydrogels by controlling their internal structure, which was monitored by neutron reflectivity. The architecture of poly(methacrylic acid) hydrogel films was tailored from well stratified to highly intermixed by regulating deposition conditions for hydrogen-bonded layer-by-layer templates used for the hydrogel fabrication. Highly swollen multilayer hydrogels, which swell up to 18 times the original dry thickness at pH=7.5, are obtained from well-stratified ‘spin-assisted&’ templates; while 3 times lower swelling is displayed by highly intermixed ‘dipped&’ hydrogels. We also demonstrated that well-stratified hydrogels exhibited a dramatic ten-fold increase in thickness when transitioned between pH=5 and 7.5 unlike the two-fold swelling observed in less organized hydrogels. These hydrogels represent a unique example of an ultrathin but highly-swollen film capable of a dramatic 94% water uptake at pH 7.5. Finally, we have found that chain conformations adopted during assembly play a crucial role in hydrogel swelling properties resulting in significant difference in the network mesh sizes at pH 7.5 at similar cross-link densities. We believe that regulating swelling behavior at the nanoscale is crucial for developing novel hydrogel-based materials with predictable and easily tunable properties.

Particles of extreme high and low mobility form dynamical clusters in cooled liquids and we focus on the geometrical nature of the immobile particle clusters presumably responsible for the growing rigidity of these materials upon cooling. These clusters are found to have many of the geometrical characteristics of a associating particle system forming a thermally reversible gel, despite the high uniformity of the density of the cooled liquid. It is suggested that infinite gel like structure of high local elasticity forms in the glass state as an extension of this particle clustering phenomenon observed at equilibrium at higher temperatures. This physical picture of a glass as being akin to a 'fractal gel' has important potential implications for the low temperature specific heat and transport properties of glassy materials and for understanding their large deformation properties.

Heterogeneously charged particles are multipolar units characterised by a competitive interplay between attractive and repulsive anisotropic interactions. We consider a selection of axially symmetric quadrupolar colloids - first introduced in Ref. [1] and referred to as inverse patchy colloids (IPCs) - in a confined planar geometry; the role of both the overall particle charge and the patch extension as well as the effect of a neutral or possibly charged substrate are studied in thermodynamic conditions such that the formation of extended structures is favoured. A general tendency to form quasi two-dimensional aggregates composed by particles with their symmetry axis oriented within the plane is observed irrespective of the confinement size; among these planar self-assembled scenarios, a clear distinction between the formation of microcrystalline gels - branched networks consisting of extended purely crystalline domains - as opposed to disordered aggregates is possible based on the specific features of the interparticle interaction [2]. The competition of particle-particle and particle-substrate interactions significantly affects the size and the internal structure of the aggregates and can even inhibit the aggregation process [2,3].
[1] E. Bianchi, G. Kahl, and C. N. Likos, Soft Matter, 7, 8313 (2011)
[2] E. Bianchi, C. N. Likos, and G. Kahl, ACS Nano, 7, 4657 (2013)
[3] E. Bianchi, C. N. Likos, and G. Kahl, in preparation

Adding particles to polymers can significantly increase their functionality by enhancing nearly any desired physical property, and can create entirely new functionalities as well, such as conductance-based sensing and field-driven actuation. In all cases the property enhancements are strongly dependent on the structure of the particle assemblies. In this presentation we will describe how multi axial magnetic fields can be used to create a wide variety of particle assemblies that greatly enhance the physical properties along any preferred axis or axes. Applications include sensors, actuators and thermal interface materials.

We present coarse-grained computations of the interactions between polymerized sickle hemoglobin (HbS) macrofibers and the erythrocyte membrane. The actin-spectrin network is locally bent and stretched as the fiber polymerizes into the membrane. The mechanics of the interaction modifies axial and radial polymerization rates, and below a critical fiber radius induces buckling of the fiber. We discuss the implications of the kinetic pathway for local strain accommodation on morphological changes of the cell as a whole, and for a more general understanding of the interactions between soft fibers and membranes.

We have tracked the mobility, approach, and annihilation of defects in cylindrical diblock copolymer thin films on nanopatterned substrates using high-temperature and time-lapse atomic force microscopy. This has been accomplished by visualizing two isolated defects and studying their approach and hence interactions. Here we used lithographed channels to template and orientationally align cylindrical diblock domains macroscopically and with low defect density. Dislocation pairs annihilate through climb and glide motion, where climb is defined as a dislocation displacement along the diblock domain stripes, and glide is defined as dislocation motion across the stripes. Defect mobility via climbing motion is observed to be faster than glide excursions. The diffusion coefficients parallel (Dpar) and perpendicular (Dperp) to the striped nanodomains have been determined; mobility along the cylinder direction is approximately one order of magnitude larger than that across the cylinders. Diffusion activation energies of both motions have been extracted from variable temperature measurements of defect mobility. Additionally, disclination pairs have been observed to annihilate by emission of dislocations and the topological switching of disclination cores. These measurements of single-defect mobility in otherwise perfected nanodomain regions allow for unusually precise determination of defect mobility and energetics for both dislocation and disclination pairs in nanoconfined polymer thin film systems.

Self-oscillating polymer gels exhibit autonomous, rhythmic swelling and deswelling due to the coupling of the swollen chemo-responsive polymer network to an ongoing non-equilibrium chemical reaction. The self-oscillations in size make these gels useful for fabricating such autonomously functioning devices as actuators and micro-pumps. Here, we discuss the computational approach to modeling gels, which swell or deswell in solvent that moves due to the imposed Stokes flow. The finite element approximation is used for descretizing the velocities of polymer and solvent within the gel and the velocity of solvent outside the gel. The system of equations for the discretized velocities is obtained by minimization of the energy dissipation potential under the gel-flow boundary conditions introduced through the Lagrange multipliers. We demonstrate application of the developed approach to modeling the Stokes flow in 2D channel modulated by the self-oscillating gel driven by the oscillatory Belousov-Zhabotinsky reaction.

Block copolymers (BCP) self assemble into periodic microdomains which if at the appropriate length scale, can act as a dielectric reflector. Moreover, these materials are quite stimulus sensitive, able to change both the layer thickness and layer index of refraction due to variationsin, for example, temperature, solvent quality, pH, salt, and mechanical forces etc. Many of the BCP based systems utilize organic solvents to swell the domains, which in an open system can evaporate over time, causing the film to shrink and change color. Ionic liquids can exhibit negligible volatility and at the same time provide both controlled layer swelling and layer refractive index. A polystyrene-b-poly2vinylpyridine (PS-P2VP) BCP having a molecular weight of 158kg/mol and 0.5 volume fraction of PS that forms a lamellar microdomain structure was swollen with the ionic liquid imidazolium bis(fluoromethylsulfonyl)imidie to create visible light reflectors spanning the blue - green portion of the spectrum. These films retain their structural color indefinitely and can even have their cross sections examined in the vacuum of a normal SEM.

Recent shear-experiments of carbopol gels have revealed the surprising formation of a transient shearband before reaching the steady state characterized by homogeneous flow. We present a computational model using Shear Transformation Zone (STZ) Theory, a phenomenological theory of plasticity in amorphous materials. Experimental data are used to determine the values of STZ Theory's parameters which best capture this observed transition and describe the structural evolution of the gel.

Current studies into systems of technological interest such as battery or fuel cell membranes often use block copolymers or blends including ion-containing polymers. An understanding of morphology, surface, and/or phase properties is typically desired to control the material in a useful fashion. For electrolyte systems, however, quantitative or even conceptual understanding into the physics governing their thermodynamics remains underdeveloped. Specifically, most current theories do not take into account the local correlation structures that are known to be non-negligible in polymers where low dielectric constants and multivalent ions are commonplace. We present a new theoretical approach to understanding these materials in a way that incorporates correlations via liquid state integral equation theories into the commonly-used self-consistent field theory formalism. We demonstrate novel physical effects, such as ion cohesion-enhancement and size-suppression of phase separation. Phase diagrams and surface tensions can also be calculated. We also incorporate the effect of salt, which is free to reorganize along the interface between the polymers. This method is versatile, and can be adapted to the increasingly-refined methods used for traditional self-consistent field theory approaches.

For decades, many researchers tried to efficiently separate salts from water. Typically, two kinds of separation methods are widely used in the industry, distillation and reverse osmosis (RO), which can produce pure water from sea water. Unfortunately, the methods are not energy efficient. In distillation process, heating up sea water to 95 degree of Celcius is required, and RO process needs a huge pressure to push sea water toward a membrane. For these energy problems, we focused on the methods of low energy water purification. Herein, we combined a temperature responsive hydrogel with forward osmosis membrane. Poly(N-isopropylacrylamide) (PNIPAM) hydrogel, which becomes hydrophobic above its LCST and expels water, was used as a pump for FO membranes. Temperature cycling a low temperature to a high temperature successfully provided a pumping action to FO membranes, resulting in continuous forward osmosis water purification. The water flux was near 0.2~2 LMH depending on the thickness of PNIPAM hydrogel and temperature cycling schedules. As the thickness became thinner, water flux decreased. When polyester fabrics were attached on the surface of hydrogel, water flux increased twice compared to non-attached fiber hydrogels. This forward osmosis layered membranes could open up a new strategy of FO water purification.

Due to the high mechanical properties and the biocompatibility, cellulose nanofibers forming 3D-networks are expected to be utilized for hydrogels. The formation of cellulose nanofibers, however, has been extremely difficult especially by using the prevalent raw cellulose beads. This was primarily due to the laborious pulverization process of the cellulose beads: harmful solvents or catalysts were utilized to collapse the strong interfacial interactions between the cellulose chains caused by hydrogen bonding. In this research, by way of using the simple, safe, and fairly new processing method (called Star Burst System (SB)), the hydrogels of cellulose nanofibers forming 3D networks were fabricated and the mechanical properties and microstructures of the synthesized cellulose nanofibers were analyzed. The SB process of making hydrogels of cellulose nanofibers was extremely eco-friendly because the process only needed water jet for the nanofiber synthesis. During the process, it was found that the nanofibers inhomogeneously dispersed in water at low pass (“pass” was defined as the number of SB process cycles) causing phase separation: upper layer of the synthetic chamber was filled with water while nanofibers were made in the lower layer separately. Increasing the “pass”, the nanofibers gradually dispersed into water: the nanofiber solution treated at 80 pass remained well in the homogeneous dispersion state over several weeks as uniform viscous solution, however in the gel state. The morphology of the nanofibers made at different pass was investigated by transmission electron microscopy (TEM). The fabricated nanofibers presented a lot of entanglements, constructing 3D networks, while the diameter of the nanofibers decreased to 20 nm with a higher aspect ratio (>100) as the processing pass increased up to 80. The effects of the pass number on the mechanical properties of the nanofiber solution were analysed. From the viscoelastic measurements, it was found that with the increase in the pass number, the storage modulus (G&’) rapidly increased from ~0.1 Pa to ~70 Pa up to 40 pass, which remained virtually constant at ~70 Pa above 40 pass. The G&’ of the nanofiber solution became higher than the loss modulus (G”), which indicated that the solution became hydrogel with the increase in the pass number through sol-gel transitions. The results clearly indicated that the hydrogels of cellulose nanofibers were successfully synthesized by SB method without using harmful substances.

Hydrogels have a broad range of applications, but are restricted by their mechanical properties. For instance, a typical hydrogel will fail at a much lower stress than an elastomer with a comparable elastic modulus. However, many aqueous applications preclude elastomers when water permeable materials are required. The development of strong, stiff, versatile, high water-content hydrogels would greatly enhance the breadth of hydrogel applications. Hydrogel toughening is often accomplished with a double network structure, in which two networks made of two different polymers interpenetrate and connect to one another with cross-links. Here we present studies of a double-network hydrogel made from polyhydroxyethylmethacrylate (pHEMA) and polyacrylamide (PA). We find that the double network dramatically improves the recoverable energy dissipation compared to a network of pHEMA alone; we observe negligible fatigue at strain values far beyond the failure strain of a HEMA network with the same polymer concentration. We have studied the structural origins of the strengthening behavior using small angle x-ray scattering (SAXS). We find that the polymers phase-separate during polymerization into nano-scale domains, controlled by the disparate polymerization rates of acrylamide and HEMA, as well as by their largely different solvation properties.

Disk-shaped colloids in the presence of adsorbing polymers show a characteristic “re-entrant” colloidal glass transition behavior. Aqueous dispersions of Laponite RD in basic conditions are known to form a repulsive glass. The addition of poly(ethylene oxide) (PEO) results in the melting of this repulsive glass and the system behaves like a viscoelastic fluid. However, as we go beyond the saturation concentration the system regains elasticity and we believe that the resulting phase is an attractive glass. We observe such a transition for systems with 2 wt% Laponite and a low molecular weight PEO (20 kg/mol). In order to comprehensively understand this re-entrant behavior, we have studied the particle-scale dynamics of Laponite samples with PEO of varying concentration and molecular weight. We compare and combine the results from rheology, dynamic light scattering (DLS) and x-ray photon correlation spectroscopy (XPCS) to examine the time-dependent structural rearrangements that occur during these re-entrant glass transitions for colloids with adsorbing polymers.

[Introduction]
Protein delivery is one of the major areas of focus for developing a highly specific and effective therapeutic technology. The protein can deliver to cells with high efficiency and activity with low toxicity for various applications in protein therapies, vaccines, cellular imaging, tumor tracking and cancer therapies by micelles or liposomes as a delivery agent. The micelles and liposomes have adhesive properties to encapsulate the drug or protein effectively and showing the enhanced absorption rate.
We have developed the polymeric cryoprotective agents, which is classified as a polyampholyte, showed excellent post-thaw survival efficiency. During freezing, ice can form in the extracellular space leading to increasing concentrations of electrolytes in the remaining extracellular solution which is called freeze concentration. Therefore, solutes in the extracellular solution could be concentrated around cell membrane. We found that our polyampholytes cryoprotectant was adsorbed onto the cell membrane during freezing. In this study, we developed the novel freezing assisted drug or protein delivery system using polyampholyte vehicles based on the concept of freezing concentration.
[Materials and method]
Polyampholyte micelles and liposomes were prepared by following methods. Epsilon-poly-L-lysine (PLL) and dodecenyl succinic anhydride (DDSA) was mixed to introduce hydrophobic part and succinic anhydride was treated to introduce carboxyl groups to form polyamphotlytes. We adjusted the ratio of hydrophobic moiety and carboxyl groups for preparing polyampholytes micelles. Also we tried directory polymerization of L-lysne, glutamic acid and phenylalanine copolymers. For polyampholyte containing liposome preparation, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and DDSA containing carboxylated poly-L-lysine mixture was extruded.
[Results and discussions]
The synthesized polyampholyte vehicles (micelles and liposome) were analysed by dynamic light scattering. These results showed that the sizes of these vehicles were around 100nm in diameter and we could control the zeta potential of by controlling the surface charges. The protein adsorption onto the polyampholyte nano-vehicles adsorption efficacy was confirmed by Bradford assay with anionic (BSA) and cationic (lysozyme) as model proteins. It was successfully we examined by the confocal laser scanning microscope that the polyampholytes vehicles deliver the FITC labelled BSA as a model protein to the cell membrane after freezing with using polyampholytes as cryoprotectants. And then it suggested that efficiently delivery of protein via endocytosis might be enhanced by using freezing.
We developed the polyampholyte vehicles which encapsulate the protein effectively and proposed the freezing assisted effective protein delivery system by using freezing concentration mechanism.

[Introduction]Stimuli-responsive materials are capable of reversibly altering their properties depending on the environmental conditions or external stimuli. Temperature is the most widely used stimulus in environmentally responsive polymer systems. The change of temperature is not only relatively easy to control, but also easily applicable both in vitro and in vivo. Temperature responsive polymers exhibit a phase transition at a certain temperature, which causes a sudden change in the solvation state. Polymers that become insoluble upon heating have a so-called lower critical solution temperature (LCST). One example of these polymers is poly (N-isopropyl acrylamide), which shows LCST at about 32 oC, close to the physiological temperature. The dish coated with this polymer has been used for temperature responsive culture dish in the tissue engineering field. In this study, we report the developing of novel polyampholytes which shows thermo-, salt-responsive liquid-liquid phase separation in aqueous solution.
[Materials and methods]The polyampholytes used in this study were carboxylated poly-L-lysines. In order to obtain these polyampholytes, 25 w/w% epsilon-poly-L-lysine (PLL) aqueous solution was mixed with various anhydrides to convert the amino groups into carboxyl groups. Initially, PLL and succinic anhydride (SA) were made to react with each other for 2hrs at 50C to make PLL-SA(0.3), PLL-SA(0.4), PLL-SA(0.5), PLL-SA(0.6), PLL-SA(0.7). Here, 0.3, 0.4, 0.5, 0.6, 0.7 denotes the introduction of carboxyl groups in 30%, 40%, 50%, 60% and 70% respectively. In order to vary the hydrophobicity of polyampholyte, we used butyl succinic anhydride (BSA), glutaric anhydride (GA), 3,3-dimethyl glutaric anhydride(DMGA), diglycolic anhydride(diGA) were used instead of SA. The change of light transmission by phase separation was detected by UV spectroscopy with temperature controlling unit and phase diagrams of various polyampholyte solutions with various cencentrations were obtained.
[RESULTS and Discussion] The polyampholyte solutions responded positively to liquid-liquid phase separation both in increasing and decreasing temperature when it was made with water and salt solution. The introduction ratio of carboxyl groups of 30%, 40%, 50%, 60%, 70% of PLL-SA showed phase separation while 20% and 80% did not show any phase separation. Moreover, the phase separation temperature of polyampholytes made with hydrophobic anhydride decreased due to the decreased solubility from the less polar groups. And hydrophilic anhydride (diGSA) reacted PLL did not show any phase separation. The phase separation temperature increased in the existence of salts. It suggested that the phase separation of polyampholytes could be ascribed to the balance between polymer-polymer attractive electrostatic force and polymer-water interactions. We will discuss the hydrogels formation of polyampholytes and their unique volume transition in different external conditions.

Injectable hydrogels have attracted a great deal of attention as cell carriers and bioactive agents in part due to their ability to fill complex three-dimensional (3D) tissue gaps and relative ease of in vivo administration. An in situ gelling and a tunable hydrogel was fabricated and characterized for mechanical performance, biocompatibility and loaded factor release. Cross-linked hydrogels were produced by the reaction between carboxymethylchitosan (CMC) and dextran aldehyde (DA) resulting in an imine bond (Schiff&’s base) formation in aqueous conditions at room temperature and neutral pH. This approach eliminated the use of additional cross-linking agents which may pose undesired side effects concerning cytotoxicity and biocompatibility. The modulus of the resultant hydrogel was shown to be dependent on both precursor composition and the degree of oxidation of dextran aldehyde. Live/Dead confocal imaging of fetal human osteoblasts seeded into the chitosan-dextran hydrogel revealed cellular viability levels above 70%, and sustained long term growth of osteoblast cells in culture. Release of bovine serum albumin into PBS media was measured at physiological temperature over 16 days and a steady release profile was obtained. With the current hydrogel design, successful controlled release of bovine serum albumin (BSA) as a model protein, as well as cellular compatibility were demonstrated in a single hydrogel design. Through the modification of hydrogel constituents the tunability of hydrogel characteristics such as modulus and swelling ratios may allow the construct to meet the demands of a myriad of tissue applications. In many tissue engineering endeavors, the need for cellular delivery and growth factor delivery come hand in hand. An injectable hydrogel capable of dual cellular and therapeutic delivery may provide an optimal vehicle for tissue regeneration. Studies are ongoing to further evaluate the performance of the hydrogel construct in vitro with clinically relevant cell populations. Future studies in vivo will provide biocompatibility evaluations in an animal model.

We report time dependent growth of NaCl crystals in dried sodium alginate samples that were polymerized in aqueous solution of calcium chloride. Sodium alginate was polymerized in aqueous solution of 0.5M calcium chloride. 1-2 mm diameter alginate spheres were synthesized by dropping aqueous solution of sodium alginate in calcium chloride solution. The dried alginate spheres were placed under the 18KeV energy monochromatic x-ray beam. The x-ray images were taken using x-ray grating interferometry performed with a single-grating spatial harmonic imaging technique. Application of this technique for grating interferometry measurement enables data acquisition at relatively high speed compared to other grating interferometry measurement modes. The measurements were performed using both one-dimensional and two-dimensional gratings at the 1-BM-B beamline of the Advanced Photon Source. Due to high-speed imaging, the photon irradiation induced crystal growth of NaCl were observed. The crystal formation was confirmed using Energy-dispersive X-ray spectroscopy (EDS).

We report the synthesis of hydrogel-nanoparticle composites where the hydrogel is the temperature-responsive gel of poly(N-isopropylacrylamide) (PNIPAm) with incorporated metal or metal oxide nanoparticles. The composites obtain nanoparticle composition and distribution of excellent homogeneity by utilizing nanoparticle brush structures as the precursor material for their synthesis. The nanoparticle brush strucures are prepared by using coupling chemistries to attach or graft PNIPAm oligomers onto metal or metal oxide nanoparticles. We describe the synthesis of bulk hydrogel-nanoparticle composites from precursor PNIPAm brush structures using appropriate cross-linkers and copolymer media. We characterized the structure of the hydrogel-nanoparticle composites using x-ray scattering and electron microscopy, and compare to hydrogel composites obtained from other methods of synthesizing such composites. We relate the ability to control the structure of the composite material by this method of synthesis to the observed properties of our PNIPAm composites and potential future enhancement of the properties of the hydrogel-nanoparticle composites.

Molecular self-assembly plays many critical roles in biology. Exhibiting important biological functions, from unfolding proteins to activating enzymes and to controlling cell fates, the assemblies of small molecules formed via supramolecular interactions, undoubtedly, are able to serve as functional molecular entities in cellular environment. Conventional biochemical and genetic methods are, however, inadequate to study the supramolecular assemblies of small molecules because they are not defined at the genetic level. We have developed the experimental strategies for controlling the formation and identifying the corresponding protein targets of the supramolecular assemblies of small molecule hydrogelators. In this talk, we discuss the emergent properties of the supramolecular assemblies of small molecule hydrogelators and report their potential applications in three closely related areas: anticancer or regenerative nanomedicine, functional mimic of biomacromolecules, protein target identification.

We describe the self-assembly of hydrophobically modified chitosan with long chain alkyl groups inserted randomly along the polysaccharide backbone. The attachment of these alkyl groups to hydrophobic particles and/or planar surfaces provides a ubiquiitous and versatile way to create hierarchical structures, particularly the formation of gels and self assembled layered materials. Such self assembly can be used in a variety of new technologies relating to biolubrication, chromatography, and the environmental remediation of oil spills through gelation of surface layers of oil. The undamental concepts of self-assembly through hydrophobic interactions will be presented through specific instances of gel formation, illustrating the range of applications that the principle can be translated to.

The double-network hydrogel concept developed by J.P. Gong and Y. Osada is that interpenetrating networks with a combination of brittle and ductile components can have significantly enhanced fracture properties. To test the generality of this concept, double-network (DN) biopolymer-based hydrogels were synthesized using copolymers of methacrylated chondroitin sulfate (MCS) and poly(ethylene glycol) diacrylate (PEGDA) as the first network and polyacrylamide (PAAm) as the second network. A double network of MCS and PAAm can reach failure stresses over 20 times greater than those of either MCS or PAAm gels. Significantly, MCS-PAAm DN gels displayed distinct yielding behaviors not previously observed in biopolymer hydrogels, with yield stresses over 1500 kPa. Similar behavior was observed with a hydrogel of MCS and poly(N,N dimethyl acrylamide) (PDMAAm). Since PDMAAm cannot hydrogen bond with the MCS in the same manner as PAAm, this suggests that specific interactions between the networks are not required for the DN effect to be observed. The relationships between the two networks required to achieve optimal properties were further explored by increasing the crosslink density of the MCS network both by increasing MCS concentration and by copolymerizing MCS with PEGDA. These changes could increase in Young&’s modulus by five times and the failure stress by four times, though increased crosslinking reduced the failure strain up to a factor of five while diminishing the yielding region. These results suggest that increases the crosslinking in the first network can stiffen the network to the point that its yield stress exceeds the failure stress of PAAm network, hence diminishing or eliminating the yielding region that results in high toughness. It is significant that these changes in mechanical properties occur with minimal changes in the swelling degrees of the DNs. Overall, this work demonstrates how a much greater range of mechanical properties can be reached in hydrogel networks generally independently of the swelling degree, which is fundamentally different behavior than is possible with single networks.

Aggregation of small molecules, as a more common phenomenon than one previously thought, can be either beneficial or detrimental to cells.1 Despite its profound biological implications, the behavior of aggregates of small molecules in cellular environment is largely unknown.2 In this work, we synthesize and characterize four fluorescent molecules, which consist of the same peptidic backbone and enzyme trigger, but bear different fluorophores on the side chain of the lysine residue of the peptide.3 These molecules, however, exhibit different ability of aggregation before and after enzymatic transformation. Fluorescent imaging reveals that the state of aggregation directly affects the distribution of small molecules in the cellular environment. Moreover, cell viability tests suggest that the biocompatibility of the small molecules is correlated with their state of aggregation and the location of the aggregates in the cell. More intriguingly, the molecular nanofibers of one of the hydrogelators apparently stabilize actin filaments and alleviate the insult of an F-actin toxin (e.g., latrunculin A). Combining fluorescent imaging and enzyme-instructed self-assembly of small molecules, this work not only reveals that the state of aggregation is the key factor for determining the spatial distribution of small molecules in cellular environment, but also illustrates a useful approach, based on enzyme-instructed self-assembly of small molecules, to modulate spatiotemporal profiles of small molecules in cellular environment for controlling the fate of cells.
Reference:
1. Silva, G. A.; Czeisler, C.; Niece, K. L.; Beniash, E.; Harrington, D. A.; Kessler, J. A.; Stupp, S. I. Science 2004, 303, 1352.
2. Gao, Y.; Shi, J. F.; Yuan, D.; Xu, B. Nat. Commun. 2012, 3, 1033.
3. Gao, Y.; Kuang, Y.; Guo, Z.-F.; Guo, Z. H.; Krauss, I. J.; Xu, B. J. Am. Chem. Soc., 2009, 131, 13576.

When two oppositely charged macromolecules in aqueous solutions are mixed a variety of materials with diverse structures and properties can be formed, due to electrostatic attraction. Under defined conditions complexation between oppositely charged polyelectrolytes can lead to a phase separation phenomenon, referred to as complex coacervation. Complex coacervation is initially seen in the form of polymer-rich fluid droplets that display a unique combination of physical properties. Using polypeptides as a model system we have previously achieved complex coacervation and studied how this phenomenon is affected by a series of parameters including pH, ionic strength, and stoichiometry. We also studied the properties of polypeptide coacervates (e.g. interfacial energy, viscoelasticity) as well as the thermodynamics of the complexation. Here, we will present how more complex molecular design can be utilized whereby a polyelectrolyte domain is connected to a neutral polymer block. These neutral domains stabilize microphase separation of the coacervate phase. For our studies we prepared ABA triblock copolymers with a water-soluble polymer (PEG) as the B block and a positively charged polymer (polypeptide) as the A block. Mixing of the triblock copolymer with an oppositely charged polypeptide homopolymer resulted in the formation of two different self-assembled structures. At low polymer concentrations nanometer-sized micelles with a coacervate core were formed. A hydrogel network generated from linked coacervate core domains was observed when the concentration of the polymers was increased. A series of experimental techniques, including TEM, SAXS, rheology and light scattering, were used to characterize the resulting self-assembled structures.

Complex coacervation is a liquid-liquid phase separation phenomenon resulting from the electrostatic complexation of oppositely charged polyelectrolytes. The resultant fluid, coacervate phase is a dense, polymer-rich liquid retaining both water and salt. Coacervates are common in everyday life, present in applications ranging from electronic displays to food and cosmetics, and are known to play a key role in the protein-based underwater adhesives used by sessile marine animals. Emerging experience has shown that the dense, amino acid-rich coacervates formed from polypeptides and other biomolecules can produce an effective biomimetic microenvironment. The liquid-liquid phase separation in a coacervate droplet enables sequestration of encapsulated materials, such as proteins, from the external environment in a manner similar to intracellular organelles. Molecular design strategies can be coupled with coacervation, linking polyelectrolyte domains to neutral polymer blocks to stabilize microphase separation into structures associated with traditional block copolymers (i.e. micelles, rods, or bicontinuous phases). This structuring, coupled with peptide-based sequence control enables the use of both phase separation and domain structuring, molecular motifs to define and control the available interactions, and thus the emergent properties of the coacervate environment on both the bulk and molecular scale.
In addition to sequence, amino acid chirality is another handle for controlling material properties. Naturally occurring proteins are composed almost entirely of left-handed, or L-amino acids. This chiral-specificity is critical for protein folding and enzymatic recognition of binding motifs. Consequently, chirality is important for maintaining the biological relevance of a particular recognition sequence. However, in the absence of sequence-imposed diversity, the fluid nature of a coacervate appears to be incompatible with homochiral polypeptides. Instead, coacervation requires a mismatch in the degree of stereoregularity between the oppositely charged polypeptides. Complexation between polypeptides with matching degrees of stereoregularity (L+L, L+D, D+L, D+D, D/L+D/L) results in the formation of solid precipitates with a β-strand structure reminiscent of the fibrils associated with amyloidogenic disorders such as Huntington&’s disease, Type II diabetes, and Alzheimer&’s. It remains to be seen patterns of chirality can be used to control macroscopic material properties such as viscosity through the formation of short crosslinking β-strand regions without altering the chemical composition.

Microfluidics has become an established technique to handle small volumes of liquids. Flow in microchannels is laminar even at high flow velocities, which allows to perform experiments under well-defined flow and mixing conditions. Kinetic processes can mapped onto a set of positions along the microfluidic channel. Therefore, time resolution is only limited by the spatial resolution of the detection method and the flow velocity. The combination with high intensity, microfocus X-ray beams allows to study fast structural changes with temporal resolution below 1 ms, while the duration of data acquisition is not affected due to steady-state flow conditions within a microchannel, which results in sufficient signal-to-noise ratios even for fast kinetic measurements.
We investigated in-situ the assembly of block copolymers into micelles and further into lyotropic liquid crystalline phases in a microfluidic channel upon mixing a block copolymer solution with a selective solvent. Using a highly intense microfocus (13x20 µm) X-ray beam at the synchrotron beamline P03/PETRAIII at DESY, we could follow the structural evolution by small-angle X-ray scattering with 10ms resolution. Our experiments with PI-b-PEO block copolymer solution show a transition from a rather disordered micellar structure which forms after several milliseconds to highly ordered cubic phases within subseconds. The observed ultrafast structural transitions can be compared to structural changes under equilibrium conditions, giving insights into fundamental differences between slow equilibrium and fast non-equilibrium phase transitions. The experiments provide first indications that interfacial trapping of block copolymers has a major influence on the topology path of structural evolution.

Layer-by-layer assembled films and capsules can be prepared from numerous materials and have therefore shown potential application in diverse fields such as energy and drug delivery. Although film deposition on planar substrates can be rapid and facile, particles generally require longer and more involved layering protocols. Recently, we reported that immobilization of template particles in a porous hydrogel allows layer deposition to be performed using rapid, facile, and automated techniques [1]. So far, we have introduced the use of electrophoresis to deposit polymers combinations on immobilized particles ranging from below 100 nanometers to above 1 micrometer. A commercially available automated dipping robot has also been modified for the automated assembly of polymers on immobilized template particles. Core-shell particles of different size, polymer composition, and functionality were obtained upon recovery from the immobilizing hydrogel. Dissolution of the particle templates yielded polymer capsules retaining the size of the templates. These techniques are rapid and versatile, and should allow various and unique functionalities to be engineered into particles and capsules with little to no manual involvement.
[1] J. J. Richardson, H. Ejima, S. L. Lörcher, K. Liang, P. Senn, J. Cui, F. Caruso, Angew. Chem. Int. Edit. 2013, DOI: 10.1002/anie.201302092.

Silk is the prototype of a fully sustainable biopolymer fiber with outstanding structural properties. The excellent mechanical properties of these protein fibers are generally attributed to a complex structural organization of the individual molecules within the fiber. Synthetic spinning attempts have so far not succeeded in preparing fibers that share the same structure and strength or toughness. We aim to develop a rigorous understanding of the molecular self-assembly of silk protein (fibroin) under different conditions. Ultimately, this knowledge can be employed to synthesize silk fibers or films with well-controlled molecular-scale organization of the protein for optimized material properties. The work presented here uses reconstituted silk fibroin (RSF), a silk dope derived from dissolved silkworm cocoons that is a popular precursor to many promising artificial silk materials. The preparation of RSF is far more efficient than the extraction of native silk fibroin (SF) from the glands of sacrificed silkworms; however, the size, rheology, and products resulting from RSF molecules have been shown to diverge from those of SF. Here, we visualize the assembly of RSF via atomic force microscopy (AFM) at the level of individual protein molecules; the measured structures are then quantitatively evaluated. We show that self-assembly of the proteins into branched fibrils can be triggered by using a spin-coating procedure to apply shear. For quantitative analysis of these structures, we used ImageJ plugins to evaluate the number, length, and tortuosity distributions of the fibrils in each AFM image. We found that the number and length of the fibrils depends on the concentration of dope. Interestingly, the mean fibril length was found to asymptotically approach 65 nm with increasing dope concentration, suggesting that the encroachment of neighboring assembled structures may limit the extension of RSF fibrils. In contrast, the assembly of native silk was subject to no such constraint, as native fibroin sheared under equivalent conditions formed a few long, straight fibrils. Our studies demonstrate that subtle changes to the protein, such as those induced through the process of reconstitution, can have dramatic effects on the structure of the assembled materials.

Severe high energy and penetrating traumas can result in acute shock and death. Emergent care at the scene is essential for optimal outcome prior to surgical care, as uncontrolled bleeding can result in death. An ideal sealant system for field use should: 1) provide consistent hemostasis for several hours; 2) adhere to the tissue; 3) be easily applied; 4) enable controlled dissolution of the sealant in the surgical setting to allow for gradual wound re-exposure during definitive surgical care. This feature is not present in any available wound hemostatic system, as removal of the clotting agent or dressing is performed via mechanical debridement and/or surgical excision. Synthetic hydrogel-based hemostats/sealants offer a number of advantages as the chemical composition, tissue adhesion, mechanical properties, degradation, swelling, etc. can be tuned. We are investigating a strategy based on thiol-thioester exchange and dendritic macromers. Herein, the design and synthesis of a dissolvable dendritic thioester hydrogel based on thiol-thioester exchange for wound closure is presented. The gel adheres strongly to human skin tissues, closes an ex vivo vein puncture and withstands high pressures placed on a wound. The gel can be completely washed off upon exposure to biocompatible thiolate solutions based on thiol-thioester exchange allowing a gradual wound re-exposure during definitive surgical care. This feature is not present in any available wound sealant, as removal of the dressing is performed via mechanical debridement or surgical excision.

We use a shear-thinning, injectable beta-hairpin peptide hydrogel with immediate rehealing behavior for sustained drug release. The advantageous rheological properties of the drug delivery vehicle result from the entangled and branched fibrillar nanostructure of the hydrogel networks. The intramolecular folding into a beta-hairpin conformation leads to subsequent intermolecular assembly of the peptides to form the peptide fibrils underlying the hydrogel network. Taking advantage of the nanofibrillar structure, the hydrogel is used to encapsulate vincristine, a common and highly effective chemotherapeutic that targets any replicating cells. Vincristine is highly effective at targeting cancerous cells at very low concentrations. However, in normal chemotherapy, large amounts of drug are used systemically in order to best affect a targeted area, resulting in many side effects. The hydrogel&’s injectability allows for targeted specificity, minimizing the need for invasive procedures or detrimental radiation treatments. Within the hydrogel, vincristine is protected from degradation by the local hydrogel environment and retains efficacy when released over time periods greater than one week. Once encapsulated, vincristine is slowly and constantly released into the local area. This allows for the lowest amount of vincristine needed to effectively target the cancer while decreasing the adverse effects on healthy surrounding tissue. Characterization of the vincristine hydrogel construct is through tritiated vincristine release, TEM, confocal microscopy, and in vitro methods.

Peptide amphiphile (PA) possesses a hydrophilic peptide coupled to a hydrophobic alkyl chain, presenting unique secondary structures (e.g. α-helix or β-sheet conformations) and micelle structures (e.g. spherical micelles and wormlike micelles) due to its active hydrogen bonding in the peptide. As the hydrogen bonding was intimately related to the environmental salt concentration, the salt concentration around PA should also be one of the key parameters dominating the structural transitions of the PA solutions. In this work, the effects of salt (sodium dihydrogenorthophosphate) concentration on the sol-gel transition behavior of our designed PA (C16-W3K) in aqueous solution were investigated. C16-W3K consisted of 17 amino-acid chains that were composed of thirteen alanines (A), one tryptophan (W) (for the fluorescence measurements to detect PA concentration), and three spatially separated lysines (K) (to increase solubility in water), which was then attached to a 16-carbon alkyl tail. The C16-W3K solution was known to present multi-scale structural transitions from spherical micelles with α-helix molecular conformations in the sol state to worm-like micelle with β-sheet conformations in the gel state. The structural transitions could be induced by external stimuli such as heat, shear, and processing time. Here, in order to analyze the effects of salt on the structural transitions, the mechanical and structural analyses were conducted by viscosity measurements, transmission electron microscopy (TEM), and circular dichroism (CD) spectra analysis. The viscosity measurements were performed by changing the salt concentrations from 0 mM to 5 mM of the 80 mu;M C16-W3K solution. The results presented the difference in the gelation speed among different salt concentrations: the faster gelation was observed at higher salt concentrations. The self-assembly microstructures of the solution were analyzed by TEM to investigate the network structures for the formation of gels. It was found that C16-W3K formed spherical micelles of 10 nm in diameter before the viscosity testing, which transformed into worm-like micelles of ~10 mu;m in length after the viscosity testing. In the C16-W3K solution without salt (i.e. 0 mM), shorter worm-like micelles of ~1 mu;m in length were observed. CD spectra showed the secondary structures of W3K in C16-W3K. Before the viscosity testing, the C16-W3K solution consisted of predominantly α-helix, while the α-helix transformed into β-sheets after the testing. In fact, the ratio of β-sheets to α-helix increased with the increase in the salt concentration.

Gelation of nanoparticle-dispersed suspension has been studied by various approaches, but the key parameters controlling the dispersion and the gelation of the suspension have been yet to be clearly defined. Here, in order to investigate the solvent concentration effects on the dispersion state of the suspension, we observed the gelation process and the networking growth of the aqueous silica-nanoparticle suspension structurally and mechanically by changing the alcohol concentrations.
Silica nanoparticles of 20 nm in size were synthesized by hydrolysis and by condensation of tetraethoxysilane with L-lysine. Ethanol and 2-propanol were separately added to the 0.4 wt% mono-dispersed silica-nanoparticle suspension at 25°C. The microstructures of the silica suspensions were observed by transmission electron microscopy (TEM). It was found that the synthesized silica nanoparticles were one-dimensionally arranged after 7 days, presenting chain-like structures when the ethanol concentration became above 70 wt%. In fact, 2-propanol realized the same one-dimensional assembly at even lower concentration of 60 wt%. The length of the one-dimensional silica-nanoparticle chains became even longer by adding more alcohol, eventually constructing 3D nanoparticle-chain networks at the concentrations of 75 wt% for ethanol and 70 wt% for 2-propanol. Such nanoparticle networks could be established within a day, which would not be decomposed into the original one-dimensional chains once the 3D networks were formed. Rheologically, the suspension with the network structures became weak gel, exhibiting non-Newtonian behavior. The storage modulus of the gel ranged from 40 Pa to 50 Pa. Zeta potential was measured and it was found that the Zeta potential was about -60 mV for pure silica nanoparticle suspension, which became nearly -40 mV by adding ethanol (up to 70 wt%) or 2-propanol (60 wt%). The addition of the alcohol led to the compression of the electrical double layer around each nanoparticle, causing decrease in the repulsive force between the nanoparticles, eventually leading to the nanoparticle self-organization. Since the dielectric constant of 2-propanol (21) was smaller than that of ethanol (26), the lower repulsive force was applied to the nanoparticles in 2-propanol, which should explain the prompt structural formation observed in the 2-propanol specimens.

Researchers have investigated hydrogels as potential materials for biological monitoring. Hydrogel compositions have been designed to respond to changes in temperature, pH, glucose concentration and ionic strength concentration. Hydrogels designed to respond to changes in environmental conditions have demonstrated their ability to respond via a swelling or shrinking action. This swelling behavior can be exploited using a variety of signal transduction methods. While this technology shows promise, the degradation of hydrogel materials has not yet been characterized with respect to the shelf life of hydrogel samples or to their use in continuous testing. A series of experiments designed to test hydrogels at various time intervals and for continuous cycles have been conducted, and have been analyzed to determine whether hydrogels can be used for extended periods of time for biological sensing applications.

Diabetes is now a worldwide epidemic and the number of sufferers is expected to reach 366 million by 2030. During the last 3 decades, extensive research efforts have been directed towards glucose measurement technologies that today account for 85% of the biosensing market. Because of the advantages in maintaining tight glycemic control, continuous glucose monitoring (CGM) has garnered considerable attention, however successes have been limited. Phenylboronic acid (PBA) is considered a promising glucose recognition agent for CGM, due to its affinity for diol-containing molecules and high chemical stability. When immobilized in a hydrogel matrix, the interaction of PBAs with glucose can produce significant volumetric changes that can report on the concentration of glucose. Although the interaction of PBAs with diol containing molecules has been intensively studied, the response of PBA-modified hydrogels as a function of the specific PBA chemistry is not well understood. We have studied, under physiological conditions, the volumetric changes of a series of hydrogels functionalized with different types of PBAs. These PBAs exhibit diverse structural parameters such as the position of the boronic acid group, different electron withdrawing and donating groups, and distance from the hydrogel backbone. We found that complex binding events between PBAs and glucose contribute to the nonlinear response: structural parameters change the magnitude and kinetics of response. None of the studied PBAs is directly suitable for CGM applications. Based on the above discoveries, we have tailored the chemical structures of both PBAs and the hydrogel matrix to achieve glucose sensing properties suitable for CGM applications. The resulting PBA based hydrogel sensor materials exhibit fast linear response, little hysteresis and no signal drift when tested in physiological buffer solutions and serum, features important to the CGM application.

This talk will describe the layer-by-layer (LbL) self-assembly of wavelength-selective photoresponsive polyelectrolyte multilayers (PEMs) that become soluble upon irradiation with visible or ultraviolet light. Random copolymerization of 2-(dimethylamino)ethyl methacrylate with a nitrobenzyl (NB) or coumarin-containing methacrylate monomer yields photoreactive polycations for layer formation by attractive electrostatic interactions with poly(styrene sulfonate). Irradiation with the appropriate wavelength of light cleaves the photoresponsive group from the polymer backbone resulting in reduced electrostatic attraction between the cationic layers causing their dissolution in aqueous base. This photochemical control of the dissolution of PEMs allows for wavelength-selective patterning of surfaces.

The study of two-component systems based on ionic liquids and organic electronic polymers is of relevance to shed light onto the working mechanism of organic transistors operated at relatively low operating voltages (ca. 1-1.5 V). Indeed, ionic liquids have been recently used as gating media in electrolyte-gated organic transistors based on organic electronic polymer films.
Electrolyte-gated transistors, where electrolytes are used as gating media to change the conductivity of a semiconductor, have been intensively investigated for low power electronic applications. [1]
Ionic liquids, for their high ionic conductivity , low volatility, low flammability and wide electrochemical windows are an important class of electrolytes to be used as gating medium.
Specifically, the capability to build a phase diagram for ionic liquids/organic electronic polymer two-component systems is the key to shed light onto the doping mechanism governing the transistor performance (electrostatic vs electrochemical mechanism).
We performed an investigation by fluorescence hyperspectral imaging and atomic force spectroscopy of two-component systems based on different weight ratios of the light-emitting polymer MEH-PPV and different imidazolium- and phosphonium-based ionic liquids, characterized by different ionic conductivity, viscosity, ion size and shape.
The performance of transistors making use of MEH-PPV and ionic liquids exhibiting a limited degree of miscibility were correlated with an electrostatic doping mode of the MEH PPV films.
[1] a) S. H. Kim, K. Hong, W. Xie, K. H. Lee, S. Zhang, T. P. Lodge, and C. D. Frisbie, Adv. Mater. 25, 1822 (2013); b) G. Tarabella, F.M. Mohammadi, N. Coppedè, F. Barbero, S. Iannotta, C. Santato, and F. Cicoira, Chem. Sci. 4, 1395 (2013).

Purpose:
The interaction between the surfactants like ethylene oxide-block-butylene oxide (EOBO) found in Opti-Free® PureMoist® MPDS and hyaluronic acid (HA) found in BioTrue MPS with the surface of the silicone hydrogel (SH) contact lens PureVision® was investigated using X-ray photoelectron spectroscopy (XPS) and friction force microscopy (FFM) as a function of ex vivo simulated wear. XPS was used to determine the degree and effect of surfactant retention at the lens surface by quantifying the amount of surfactant present in the near surface region following simulated wear. FFM was used to investigate the effects of the present surfactant on the lens friction response in an aqueous environment.
Methods:
All measurements were conducted on commercial PureVision® lens samples. Following a 24 hour soak in a phosphate buffered saline (PBS) solution, lenses were stored in the commercial cleaning solutions Opti-Free® PureMoist® or BioTrue for 24 hours. Lenses were then subjected to simulated wear through agitation at 26 Hz in a PBS/hydrogel slurry for finite periods of time. Lens samples were prepared for XPS analysis through a vacuum drying procedure. The chemical compositions corresponding to uppermost 10 nm of the surface were probed by XPS for each sample, monitoring the spectroscopic signature of the respective surfactants contained within the cleaning solutions. Friction coefficient for the sliding contact of the lens samples and a 5-mu;m (diameter) silica colloidal probe was measured by FFM. Friction force measurements were carried out in PBS at the speed of 1 mu;m/s and a sliding distance of 1 mu;m.
Results:
Simulated wear of the treated lenses resulted in a reduction in the molecular quantity of surfactant found in the near surface region with a greater reduction in the quantity of HA as compared to EOBO for identical wear regimens. Furthermore, respective changes in friction coefficient of the lenses undergoing simulated wear reflected the reduction in amount of surfactant. EOBO treated lenses demonstrated a reduced friction response even after simulated wear while the effects of HA treatment on the friction response of the lenses were negated by simulated wear.
Conclusions:
The correlated results of friction and surface composition demonstrate the potential for the modification of lens surface properties through solution treatment, with effects that may persist throughout the period of lens wear.
Disclosures: Support: Grant from Alcon Research, Ltd.

Thermoplastic starch (TPS) is an attractive material having potential to replace polymers produced from fossil fuels commonly used in applications such as packaging, agricultural, biomedical among others. It has advantages such as biodegradability, wide availability and low cost; however it presents changes in its properties due to molecular reorganization in the production process and changes in time, which depend on the production protocol and storage conditions, limiting its use leading to studies using reinforcements such as clays (Phyllosilicates) to enhance the material stability. During TPS production and life cycle, complex phenomena involving the rearrangements of polysaccharide molecules, such as gelatinization and retrogradation (recrystallization), take place (Chivrac, Pollet, & Avérous, 2009). The gelatinization process is necessary to obtain a thermoplastic material (the TPS) from native starch granules This process involves the addition of a plasticizer which diffuses into the starch granules, generating their growth to achieve the dissolution and interpenetration of the granules (Teyssandier, Cassagnau, Gérard, & Mignard, 2011). The gelatinization process can be affected by process variables as the heating rate, the starch botanical source, the starch/plasticizer ratio, and fillers addition, among others. This work presents a systematic rheological study of the gelatinization process of two different kinds of starch (corn and cassava) plasticized with glycerol, showing the effects of the glycerol/starch ratio, starch amylose content (according to the botanical source), heating rate, and montmorillonite (mmt) content. Gelatinization times at several temperatures in isothermal time-sweep experiments and gelatinization temperatures at different heating rates in temperature-sweep experiments were determined for different Starch/Glycerol/mmt formulations. The gel properties of the different TPS/mmt composites produced were studied in frequency-sweep experiments at different temperatures. Time-temperature superposition principle was used to overlap the data coming from the frequency-sweep experiments and shift factors and activation energies at different temperature range were evaluated. As a result, it was shown that all studied variables have an important influence on the gelatinization and retrogradation phenomenon, and on the gel properties of the different systems analyzed. Some hypotheses postulating how the different intermolecular interactions present in the composites are responsible for these effects are discussed.
Chivrac, F., Pollet, E., & Avérous, L. (2009). Progress in nano-biocomposites based on polysaccharides and nanoclays. Materials Science and Engineering: R: Reports, 67(1), 1-17. doi:10.1016/j.mser.2009.09.002
Teyssandier, F., Cassagnau, P., Gérard, J. F., & Mignard, N. (2011). Sol-gel transition and gelatinization kinetics of wheat starch. Carbohydrate Polymers, 83(2), 400-406. doi:10.1016/j.carbpol.2010.07.061

The temperature phase transitions of thermosensitive polymer aqueous solution triggered by various external factors have been widely studied. In this research, hydroxypropyl methylcellulose (HPMC) as an example of thermosensitive natural polymer was selected to study acrylic acid (AA), methacrylic acid (MAA), DL-lactic acid(LA), critic acid monohydrate(CA) and acetic acid(AAc) how to affect the temperature phase transition of HPMC by using UV-visible spectrophotometer. The experimental results are summarized as follows. In an acidic acid solution of pH=3.0, AA, MAA, LA, and CA triggered the phase transition of HPMC at a lower temperature. The triggering effect of MAA was the strongest, that of AA stronger, that of LA and CA weak, while AAc nearly made no difference. AA, LA, CA and AAc continued to lower the temperature phase transition with the increase of pH values, and AA made a weaker effect compared to another three acids. In contrast to another four acids, MAA caused the phase transition to occur at a higher temperature. Based on the phase transition of HPMC solution triggered by MAA, PMAA nanogels have been synthesized and characterized by using dynamic light scattering (DLS) and Fourier Transform Infrared Spectroscopy(FTIR). The synthesized PMAA nanogels were affected by the concentration of both HPMC and MAA: a higher concentration of MAA led to a higher polymerization rate and a higher concentration of HPMC resulted in a larger particle size of the nanogels.

DNA has been proved as an excellent building material for the construction of precise and switchable nanostructures, owing to its specific base-pairing recognition, designable sequences and clear secondary structures[1]. Apart from building nano- or micro- scale objects, we have used well-designed DNA nanostructures as building blocks to fabricate bulky materials, e.g. self-assembled DNA hydrogels[2]. They have biocompatibility and designable mechanical properties and smart responsiveness to external stimuli, such as pH[3], enzyme and temperature[4]. These characteristics have endowed DNA hydrogels with promising applications in biomedical areas. For example, they have excellent performance in controllable release of nanoscale species for drug delivery, however, it is still very difficult to apply them to mammalian cell, especially in single cell level, which possesses important significance in drug screening, monoclonal antibody selection, early diagnosis and other biomedical applications.
Herein, we develop an enzyme-triggered DNA hydrogel cover system which functions as a smart gatekeeper to envelop and release single cells in PDMS microwells[5]. Single cells are firstly trapped in a PDMS microwell array chip at optimized microwell diameter and seeding cell density. By adding DNA building blocks onto the microwell chip, a layer of DNA hydrogel film forms in situ to cover the microwells, thus, single cells are enveloped separately in each microwell. Notably, compared with other cover systems, the porous structure of DNA hydrogel allows effective diffusion of nutrients and waste, leading to a cell viability as high as 98% after incubation for 24 h. After cell culture, the DNA hydrogel cover can be digested by a specific restriction enzyme, and the cells can therefore be released in a controllable way for further analysis and detection. This work provides a new platform to culture, monitor and manipulate single cell controllably and can potentially extend to many other biomedical applications.
[1] N. C. Seeman, Nature 2003, 421, 427.
[2] D. Liu, E. Cheng, Z. Yang, NPG Asia Mater. 2011, 3, 109.
[3] E. Cheng, Y. Xing, P. Chen, Y. Yang, Y. Sun, D. Zhou, L. Xu, Q. Fan, D. Liu, Angew. Chem. Int. Ed. 2009, 48, 7660.
[4] Y. Xing, E. Cheng, Y. Yang, P. Chen, T. Zhang, Y. Sun, Z. Yang, D. Liu, Adv. Mater. 2011, 23, 1117.
[5] J. Jin, Y. Xing, Y. Xi, X. Liu, T. Zhou, X. Ma, Z. Yang, S. Wang, D. Liu, Adv. Mater. Accepted.

The particle migration under the external force (F) is influenced by the friction (zeta;) or mobility (mu;) as v = F/zeta; = mu;F, where v is the velocity of particle. Especially, in the case of the charged particles under the electric field (E), v is given by v = QE/zeta; = mu;_eE. Notably, mu;_e contains the unit of the electric charge. Because the size of the particles and the structure of medium influence the frictions between the particles and medium, particles with different sizes migrate at different velocity in proper medium. Gel electrophoresis, which separates polyelectrolyte sequences based on their sizes using polymer network as medium, is the most popular application of this phenomenon. Because gel electrophoresis is invaluable in fractionating biopolymers, the migration mechanism in polymer network has been extensively studied.
The relationship between mu;_e and polyelectrolytes length is both theoretically and experimentally confirmed, but the relationship between mu;_e and polymer network structure is poorly understood. The definable correlation lengths of polymer network are concentration blob (xi;_c) and elastic blob (xi;_el). xi;_c, observed by small angle neutron scattering, is independent of polymerization degree of network strand (N) and depends only on the polymer volume fraction (phi;). xi;_el, observed by mechanical testing, corresponds to both N and phi;. Although there are a few papers trying to investigate the effect of xi;_c and xi;_el on mu;_e independently by changing the crosslinking concentration, there was no detailed discussion. The reason inhibiting the investigation of the effect of xi;_c and xi;_el is the uncontrollability of xi;_el, which is caused by the heterogeneous nature of conventional polymer gels. Therefore, it is practically impossible to investigate the pure effect of xi;_c and xi;_el on mu;_e.
Recently, we have succeeded in fabricating a homogeneous gel system (Tetra-PEG gels) by the A-B type crosslink coupling reaction of two mutual reactive tetra-armed poly (ethylene glycol) (Tetra-PEG pre-polymers). Extremely homogeneous structure was confirmed by small angle neutron scattering. In addition, we can precisely control the structural parameter including xi;_c and xi;_el by tuning the molecular weight and polymer volume fraction of pre-polymers. A series of precisely controlled polymer networks will be helpful in understanding the migration mechanism of polyelectrolyte in polymer gels.
In this work, we used precisely tuned Tetra-PEG gel as separation medium and carried out capillary electrophoresis for rod-like dsDNA in order to investigate effect of xi;_c and xi;_el on mu;_e. We found that xi;_c and xi;_el affected mu;_e independently for the first time in the world and the rod-like dsDNA does not follow conventional theory for gel electrophoresis. Finally, we successfully proposed a new model for migration of rod-like dsDNA in polymer network. This model suggests that controlling the xi;_el precisely can increase separation performance significantly.

The behavior of materials confined at the nanoscale has been of considerable interest over the past two decades. Recent work in our laboratory has focused on the influence of nanoconfinement on the glass transition and associated kinetics, on melting and crystallization, and on polymerization kinetics and resulting properties. In this talk I will present results investigating the depression of the glass transition temperature for nanoconfined polycyanurate materials, as a function of crosslink density and molecular size. The materials are confined in cylindrical nanopores and are polymerized in situ. The polymerization kinetic model and conversion at gel point do not change under nanoconfinement although the rate constant increases with decreasing pore size. The results will be discussed in the context of the leading explanation for the Tg depression in nanoconfined glasses, i.e., that the mobility arises from free surface and interface affects.

Collagen/hydroxyapatite (Co/HAP) composites exhibit reasonable balance of physical and biological properties desired for scaffolds for bone tissue engineering providing uniform mesenchymal stem cells (MSCs) distribution, proliferation and differentiation into osteoblasts ex vivo. Hierarchical Co/HAP composite superstructure is formed by bottom-up self-assembly of the nano-scale building blocks (NSBBs), consisting of HAP nanoparticles and Co triplehelices, in aquaeous environment, forming hierarchical superstructure constantly adapting to external stimuli. This results in significant time dependence of the Co/HAP composite network structure and, consequently, hydrogel viscoelastic properties. Hence, time, frequency and amplitude dependence of viscoelastic properties of Co/HAP hydrogels with varying composition were measured to relate the structure evolution to the evolution of viscoelastic properties.
Effect of HAP (specific surface area of 190 m2/g) content and Co concentration on the storage moduli (G') of model nanocomposite hydrogels was analyzed at small oscilatory deformation considering molecular self-assembly processes occuring at the dimensions of individual collagen molecules and their microfibrils formed over time period up to 104 s. We attempted to describe the Co network stiffening mechanism at the nano-scale and the controlling role of the Co-HAP interface area. An "immobilized chain percolation network" with individual chains obeying Langevin equation with randomly distributed HAP nanoparticles 10 nm in diameter was demonstrated to provide reasonable means for analyzing the instantineous viscoelastic response of the Co/HAP nanocomposite hydrogels. Time dependence of these properties was shown to be a result of self-assembly of Co tripple helices into more rigid larger scale fibrils. During the first 5x103 s, G increased 3-5 orders of magnitude. This process seems thermodynamically similar to chain crystallization. As shown previously, presence of nanoparticles slows this process down considerably compared to neat polymer by greatly reducing their diffudion coefficient. It was shown that there is a critical HAP concentration above which the self-assembly of Co triplehelices is completely prevented. Surprisingly, this critical concentration is close to the amount of HAP in mineralized collagen fibrils found in human femur bone.

Acknowledgement
Funding under the project CEITEC, CZ.1.05/1.1.00/02.0068 from the European Regional Development Fund is greatly appreciated.

Understanding the diffusion of nanoparticles embedded in a complex medium is relevant to many technological and biological processes. Recently, we have exploited the advantages of fluorescence correlation spectroscopy (FCS) and time-lapse confocal fluorescence microscopy (t-FM) to investigate movements of various nanoparticles within different polymeric and cellular systems. In particular, we have focused on two model polymer systems: Poly(vinyl-alcohol) (PVA, MW=85 kDa) and Ficoll (MW=70 kDa). PVA is a neutral, water-soluble, linear polymer commonly used in tissue engineering. Ficoll is a water-soluble, highly-branched sucrose-polymer used in perfusion experiments and studies of the crowding effects. Further, we have extended our work to studies of the movements of biological nanopathogens in mucus. Both FCS and t-FM techniques are relatively non-intrusive, allowing us to monitor in situ interactions of various fluorescent nanoparticles in non-fluorescent - hence “invisible”- synthetic and natural polymeric solutions and gels.
We have measured characteristic times of several globular, branched, and linear nanoprobes [rhodamine (~1.8 nm); BSA (~7 nm); phycoerythrin (~10 nm); polystyrene beads (~28, 44-nm); linear labeled PVA (~18 nm); branched dextran and ficoll (~3 and 11 nm)] diffusing in PVA or Ficoll solutions as a function of the polymer concentration, exploring different lengthscales set by the polymer-polymer correlation length. For small globular and linear nanoprobes, the decrease of the diffusion coefficient (D) with increasing polymer concentration (c) cannot be accounted for by the Stokes-Einstein relation. Instead, the decrease can readily fitted with a stretched exponential, exp(-Bc^n), where n is related to the solvent quality, as suggested by de Gennes and co-workers. For PVA solutions we find 0.73 le; n le; 0.84 (good solvent) and a linear relation between B and the size of the globular nanoprobes. In contrast, n = 1 for Ficoll, suggesting a theta-like behavior of the Ficoll-water solutions. However, for large probes (> 25 nm), FCS and t-FM data can be analyzed within the Stokes-Einstein relation, allowing us to determine changes the viscosity of the host medium with changes of the polymer concentration.
Cross-linking of PVA chains to form gels can further slow down the diffusion of some rhodamine. The more the polymer chains are cross-linked, the slower the nanoparticles diffuse. Remarkably, we find a simple linear relation between the elastic modulus of the PVA gels and the diffusion time of the nanoprobe. We have also studied the effect of drying on the nanoprobe diffusion and elastic modulus of the PVA gels, prepared at different concentrations and cross-link density. The results obtained from these two model polymeric systems will be contrasted to those obtained in samples of mucus, a highly heterogeneous biological system, in which nanopathogenic particles are embedded.

We investigated the rheological properties of Hyaluronic Acid (HA)-Clay, gelatin-Clay and HA-gelatin-clay hydrogels of different stiffness&’s prepared by physically crosslinking HA and gelatin with inorganic clay. Resulting hydrogels were transparent and mechanically stable. The oscillatory stress sweep measured G' as a function of stress and frequency sweep traced the evolution of G&’ and G” over time. Results from frequency sweeps suggested the formation of a stable, three dimensional networks while the stress sweep revealed the linear viscoelastic region and the breaking stress of the hydrogels. HA-gelatin-clay hydrogels were observed to have highest G&’ and the G&’ increased with the increasing polymer to clay ratio. Dermal fibroblasts adhesion was seen on HA-gelatin-clay hydrogels for a period of 3 days and cell modulus was observed to be higher on a stiffer substrate. Effect of glucose, a physiologically relevant additive, at the diabetic concentration showed that the modulus of HA-clay hydrogel was dramatically reduced causing ‘collapse&’ of the gel. Lastly, the controlled Salicylic acid release from HA-clay hydrogel established its application as a drug delivery vehicle.
Such a detailed rheological characterization and knowledge of cell cultivation and controlled drug release of our HA-clay hydrogels with no chemical additives will aid in the design of biomaterials targeted for biomedical or pharmaceutical purposes, including rigid cell scaffold structures.

The nanostructure of calcium-low-methoxyl-pectin gels is still not fully understood despite its wide use in food and biomedical devices. In this study we present a comprehensive small angle X-ray scattering (SAXS) analysis of calcium-pectin gels with various calcium concentrations. Several modeling approaches were examined taking into account the contribution from both junction zones and chains between cross-links. The SAXS studies are supplemented by determination of the gels&’ mechanical properties and swelling behavior. The model of semiflexible chains without excluded volume effects was found to be most suitable for describing calcium-pectin gels. The SAXS analysis suggests that both rod-like junction zones and point-like cross-links between neighboring chains are formed in calcium-pectin gels. Moreover, as the calcium content increases, the number of the rod-like junction zones decreases while the number of the point-like cross-links increases.

Because of their large potential in biorelated applications, hydrogels post-modulable in desired time and space domains become of particular interest. Toward this goal, most promising are photolatently reactive hydrogels. We took note of mechanically tough composite hydrogels structurally supported by polymer networks physically crosslinked with clay nanosheets. Titania photoconverts water into hydroxyl radicals that can polymerize vinyl monomers. By using titania nanosheets (TiNSs) instead of clay, we developed photolatently modulable hydrogels, composed of a polymer network featuring photocatalytic TiNS at every crosslinking point. Since TiNS can utilize gelling water as the source of radicals, its long-lasting photocatalysis, in principle, makes the hydrogels modulable multi-times on-demand. Benefiting from the hydrogelation mechanism, the gel network is finely compartmentalized, leading to sharp thermoresponsive behaviors. As demonstrated by photo-micropatterning, non-diffusible TiNSs at the crosslinking points enable pointwise post modulations with an excellent spatial resolution. The photolatent nature also makes it possible to conjugate with other hydrogels and polymers.

An electric-field-assisted method was developed for fabricating layer-by-layer(LBL) self assembly multilayer films. LBL method is based on the alternate adsorption of oppositely charged materials in aqueous solutions via electrostatic attraction. It has many advantages such as a simple process, water-based room-temperature deposition at normal pressure, no limit of thickness, and no need for complicated equipment. In addition, the thickness of the thin films can be controlled with nanoscale accuracy. Although this method has many advantages, it requires a long fabrication time. Because the process is driven in part by diffusion, LBL cycles usually take several minutes to complete. This is an unacceptable demerit if this technology is to be applied in industrial fields. To solve this problem, the spray LBL method, in which solutions are sprayed directly onto substrates, has been developed. Moreover, applying external force to the LBL process has been attempted to enhance adsorption. In recent study, LBL method under applied voltage attracts great attention.
We investigated the electric-field-assisted LBL assembly of polyelectrolyte and a nano particle under electric fields on the non-conductor glass substrate. Two Pt electrodes were inserted parallel into the bath, and the distance between cathode and anode was 3 cm.A voltage was imposed on the two electrodes by a DC power supply during the assembly process. We report on surface structure in response to the applied electric field. And we reported that applying voltage in LBL method is effective in control film adsorption, structure and transmittance. The fabrication speed of thin film was increased by applied voltage at the fabrication of thin film by LBL method. It is expected that the electric-field-assisted method is very useful for the fabrication of functional thin films for optical devices, filters, and sensors, or various surface coatings.

Under acidic conditions, hollow silica nanospheres (HSNs) have been successfully fabricated using a commercially available triblock copolymer surfactant as the soft template. The single-micelle-templating strategy provides a general approach for the synthesis of HSNs, including those with functional moieties. The judicious choice of the reaction mixture composition (e.g., addition of swelling agents) allowed us to obtain well-defined HSNs with tunable pore structures and high surface areas. This facile approach can also be employed to the construction of well-defined organic-functionalized HSNs. Thermogravimetry, IR, transmission electron microscopy, gas adsorption and small-angle X-ray scattering were used to characterize the obtained nanospheres.

Block copolymer thin films have shown high potential as a pattern transfer medium for ultra-fine (<20 nm) features. We employ an approach for performing rapid local annealing of block copolymer films by focused laser spike (FLaSk) zone annealing, using a moving highly-focused circularly polarized visible wavelength laser spot. The absorption of the underlying substrate generates a thermal spike possessing extreme spatial and, with sample motion, temporal gradients (estimated as 100-750 K/µm and 3,000-75,000 K/s respectively depending on write speed, power, and laser focus). Using these gradients as a driving force for annealing of microphase separation and alignment of the microdomains, a polystyrene-polydimethylsiloxane block copolymer was transformed from a metastable spherical micelle morphology to the bulk equilibrium cylindrical morphology aligned along the write direction within a region controlled by manipulation of the laser focal plane. The efficacy of this process was further enhanced by incorporation of solvent swelling of the block copolymer film with toluene vapor by expected mobility, surface energy, and cooling effects. This simultaneous microdomain reordering and alignment was accomplished on the tens of millisecond time scale with larger temporal gradients leading to the highest level of alignment.

Over the past two decades, porous materials have been rapidly advancing in recent years because of their high porosity, large surface area and light-weight. However, most of established porous materials are rigid, prepared from metal oxide and metal complex based materials, and pore size is tunable only below ~10 nm. Therefore, their hosting ability is limited only for very small compounds and not favorable for accommodating nano- or submicron-sized objects. In the effort to facilitate the raising demand in biotechnology applications for encapsulation and separation of protein, where biomolecules with bulky molecules are involved, development of porous materials with void dimension in the range of meso-/macro-pores is strongly needed. Polymeric porous materials would be a perfect candidate to answer this challenge due to their excellent properties derived from both high porosity and flexibility of polymers, such as high surface area and porosity, easy and low cost processing, pore size can be controlled in mesoscopic range, light-weight and tunable properties and functionalities. Up to now, self-assembly based upon block copolymers (BCPs) has been developed as one of the best strategies for the preparation of meso-/macroporous polymers. Nonetheless, the applications of porous materials from BCPs are limited by multiple and cumbersome steps that involve in their preparation processes. Therefore, preparation of polymeric porous materials with a simpler method is strongly desired for their future application. Also, to our best knowledge, most of polymeric porous architecture is just rigid and does not possess tunable softness or fluid-like property. Polyion complexes (PICs) technology offer a facile and “green” preparation method of materials, since PICs can be directly obtained in an aqueous medium immediately after the mixing of oppositely charged polymers. In this study, we report a new type of soft polymeric porous materials from PICs prepared by simple mixing of a set of oppositely charged double hydrophilic block copolymers. This facile synthesis and designable architecture is advantageous for environment-friendly and low-cost fabrication of porous materials. Pore sizes of mesoporous PICs can be tuned between around 10-100 nm by changing polymer compositions, and varied in response to thermal treatment. Some specific shape can be fixed by crosslinking of PICs. Moreover, this porous architecture can accommodate nano-/submicron-sized materials with high loading efficiency (~70% of feed nanoparticles) during self-assembly process. Therefore, mesoporous PICs is potentially useful as a versatile platform of polymeric mesoporous materials. Also, porous PICs reported here are promising for biomedical applications and anti-fouling materials due to their fully pegylated structure.

Peptides have become attractive molecules for fabricating biomaterials. Studies of peptide structure, assembly properties, and dynamic behavior in response to external parameters have led to rational novel design of peptide biomaterials. One model sequence selected was a β-spiral motif of spider flagelliform silk protein, [GPGGX]n (X = any amino acid). Modifying the X residue can change the quantity of secondary structure and the stability of this spider silk motif. Glycine provides flexible properties, and proline influences the secondary structure and mechanical properties. Another model sequence was GXGXDXUX (U = hydrophobic residue), a Ca2+ binding domain of lipase Lip A from Serratia marcescens, in which aspartate residue is required for ion binding. Combining with [GPGGX]n, we rationally designed peptide as GPGGDGPGGD (eD2). The Ca2+ binding sequence was hidden in the first eight residues of eD2. As expected, this peptide can assemble into nanofibrils triggered by Ca2+ ions. Using the segment FLIVIGSII (h9) from the third trans-membrane segment of subunit IV in the dihydropyridine sensitive human muscle L-type calcium channel as the hydrophobic motif, we obtained FLIVIGSIIGPGGDGPGGD (h9e) peptide. The h9e self-assembled into nanofibrils and further formed shear-thinning and rapid recovery hydrogel in neutral pH range from 6.0 to 8.0 and stable in large temperature range. To further understand the contribution of each native region of h9e for hydrogel formation, a series of peptides were synthesized by modifying the primary structure of h9e. We identified that the turning segment GSII of h9e promoted self-assembly and hydrogel formation in the presence of triggers with water content greater than 99.5%. The h9e hydrogel was biologically safe and has great potential biomedical uses. This presentation will also provide a few potential application examples, such as drug delivery, 3D cell culture, and wounds healing.

Microcapsulation is the technology which utilizes natural or synthetic polymer wall materials to cover solid particles, liquid droplets or gas core materials, forming particles with diameters in the micro range about 1~1000 micron. Microcapsule technology, born in the nineteen fifties, was originally applied to the production of carbonless copy paper. In recent years, it has been successfully applied to areas of stationery, medicine, high-profit specialty chemicals, pesticide, liquid crystal device etc.
In this paper, polyisocyanate and polyamine is utilized by interfacial polymerization to prepare peppermint oil microcapsule and mentholated camphor microcapsule with different encapsulation efficiency as well as cantaloupe and rose-smelling microcapsules. We studied the capsule through thermogravimetric analysis determining the thermal stability and Fourier transform infrared spectrum analyzing the residual of polyisocyanate in the microcapsules. And we observed the morphology of the microcapsule and mechanical stability after drying through SEM, and the size of the microcapsule and mechanical stability after drying through optical microscope. Laser particle size analyzer was utilized to measure the size and size distribution of the microcapsules. Experimental results indicate that novel fragrance microcapsules prepared with larger embedding rate have very low unreacted monomer and display strong mechanical strength, and will find applications in liquid detergent, softener, shampoo, hair conditioner, and etc. Furthermore, fragrance hydrogels have been prepared by dispersing the microcapsules in aqueous monomer solution and polymerizing and crosslinking the monomers. The fragrance hydrogel will promise to become a new generation of air freshener .

Phenol derivative-containing adhesive hydrogels has been widely recognized for potential biomedical applications, but conventional methods utilizing moderate/strong base, alkaline buffers, addition of oxidizing agents, or use of costly enzyme, have required alternative approaches for improved biocompatibility. In this study, we report a polymeric, enzyme-mimetic biocatalyst, hematin-grafted chitosan (chitosan-g-hem) that results in effective gelation without use of oxidizing agents or enzymes. Furthermore, the gelation occurs at a mild physiological condition. The use of chitosan-g-hem biocatalyst (0.01%, w/v) had excellent catalytic properties, forming rapid chitosan-catechol hydrogels within 5 minutes. In vivo adhesive force measurement demonstrated that the hydrogel formed by the chitosan-g-hem activity showed an increase in adhesion force (33.6 ± 5.9 kPa) compared with the same hydrogel formed by a pH-induced catechol oxidation (20.6 ± 5.5 kPa) in mouse subcutaneous tissue. Using the chitosan-g-hem biocatalyst, other catechol-functionalized polymers (hyaluronic acid-catechol and poly(vinyl alcohol)-catechol) also formed hydrogels, indicating that the chitosan-g-hem can be generally used as a polymeric catalyst for preparing catechol-containing hydrogels.

The capacity to probe depth-dependent dynamic structural changes induced by photochemistry is a vexing challenge in photolithography, rapid prototyping, dental composite restorative resins, the development of other photo-crosslinked tissue engineered scaffolds and in other areas where both light absorption and the presence of oxygen can stratify reaction responses to the illumination exposure. The purpose of this contribution is to present algorithms and protocols to account for conversion stratification in cationically photo-crosslinked epoxy resins. Necessary data sets of depth-dependent viscosity and conversion are required, such as that generated by magnetic microrheometry, linked with other characterization tools such as depth-dependent, real-time FTIR, DSC, and UV visible spectroscopy. By applying dynamic viscosity models such as the Boltzmann sigmoidal model, time constants associated with the rapidity of conversion can be extracted. And from model extractions from dynamic viscosity measurements as functions of both photoinitiator concentration and more broadly overall formulation, a more comprehensive view of how conversion stratification can be deduced that could lead to alternative formulation schemes to reduce shrinkage stresses. I will present the protocol relating to published conversion data using bis 3,4, (epoxycyclohexylmethyl) adipate crosslinked by a mixed cationic photoinitiator triarylsulfonium hexafluoroantimonate salt as a model system, and describe how models can be adjusted to more accurately represent measured dynamic responses or to extrapolate to regions of higher conversion approaching the gel and glass regions.

Chondroitin sulfate (CS) is a highly negatively charged component of proteoglycans and mammalian extracellular matrix (ECM) and as such has been investigated by a number of groups for its potential as a tissue engineering scaffold when crosslinked into a gel. Photopolymerization of methacrylated chondroitin sulfate (MCS) in aqueous solutions of 10 - 40 w/w% forms soft (relatively low modulus) hydrogels and which limits practical application. However, crosslinking of MCS with small amount (e.g., 0.06 mol%) of oligo(ethylene glycol) diacrylates ((EG)n-DA) significantly increased the compressive shear and Young&’s moduli. Increase in moduli was amplified with increases in the degree of methacrylation (DM) of chondroitin sulfate and the number of ethylene glycol repeats in the crosslinker. Transient mechanical analysis showed that increasing methacrylation from 30 to 40 mol% and increasing (EG)n-DA length from n=1 to n=13 resulted in a 2 to 25-fold increase in the elastic and shear moduli and significant reduction in the swelling ratio compared to parent MCS hydrogels. The improvement of the moduli was determined to be the result of efficient copolymerization of acrylate groups on the PEGDA with the methacrylate groups on the MCS in the growing kinetic chains, hence leading to higher crosslink densities. However, analogous methacrylate crosslinkers reduced the crosslink density of the MCS due to the similar reactivity ratios of the methacrylate groups on the two macromers. Although the OEGDAs were effective in increasing the modulus of the MCS gels, for all such gels the fracture strain in water was ~20%. The insensitivity of the fracture strain to crosslink efficiency is believed to be determined by the chain conformation of the MCS and the limited number of statistical chain segments in these polyelectrolyte gels. The moduli of poly(ethylene glycol) gels was similarly increased with addition of small amounts of MCS due to increased crosslink efficiency as the MCS functions as a multifunctional and degradable crosslinker. These results demonstrate a simple, practical way to improve the modulus of methacrylated biopolymer gels generally.

Conjugated polydiacetylenes have attracted great interest in the view of sensors by virtue of the bichromatic properties from blue to red and self-emitting fluorescence properties from non-fluorescence to red fluorescence. Solid-state sensor matrixes which have stability, advantage of easy handling, and long period of shelf life are required for the step forward development of polydiacetylene sensors. In this research, polydiacetylene sensory platforms were designed by adopting porous silica plates and diacetylene monomers. A strategy of coating diacetylene on the porous plate is to dip a silica plate in the monomeric solution, resulting in long uprising behavior via solvent capillary action. This strategy has merits to use monomers instead of vesicles which show less stable property and to fabricate sensory platforms within 1 minute. New polydiacetylene platforms were successfully applied to detect ammonia gases and oligonucleotides within 30 minutes.

Synthetic hydrogels have been widely investigated as artificial extracellular matrices (ECMs) for tissue engineering in vitro and in vivo. Crucial challenges for such hydrogels are sustaining long-term cytocompatible encapsulation and providing appropriate cues at the right place and time for spatio-temporal control of the cells. Here, we report in situ supramolecularly assembled and modularly modified hydrogels for long-term engineered mesenchymal stem cell (eMSC) therapy using cucurbit[6]uril conjugated hyaluronic acid (CB[6]-HA), diaminohexane conjugated HA (DAH-HA), and drug conjugated CB[6] (drug-CB[6]). The eMSCs producing enhanced green fluorescence protein (EGFP) remained alive and emitted the fluorescence within CB[6]/DAH-HA hydrogels in mice for more than 60 days. Furthermore, the long-term expression of interleukin-12 (IL-12) by eMSCs within the supramolecular hydrogels resulted in effective inhibition of tumor growth with a significantly enhanced survival rate. Taken together, our findings confirm the feasibility of supramolecular hydrogels as 3D artificial ECMs for various cell therapies and tissue engineering applications.

We recently reported a novel approach for synthesizing various nanostructured materials by employing irreversible covalent self-assembly of rigid, disk-shaped building blocks having laterally predisposed reactive groups on their periphery without any aid of templates or pre-organization of the building blocks. From a synthetic chemist's point of view, irreversible covalent self-assembly is equivalent to performing a one-pot reaction that results in complex structures through bypassing many unnecessary multi-step synthetic procedures. Such self-assembly is driven by intrinsic factors present in the building blocks such as size, shape and directionality of bond formation as well as external factors such as the polarity of the reaction medium. Many interesting polymeric nanomaterials can be produced with specific size and shape through proper control over the self-assembly conditions and design of the building blocks. Until now, we have successfully demonstrated the template-free synthesis of polymer nanocapsules, 2D polymers with single monomer thickness, and hollow nanotubular toroidal polymer microrings by controlling these intrinsic factors, which offer a wide range of applications including drug delivery, photodynamic therapy, sensors, and molecular separation. The details of the work will be presented.

Controlling polymer morphology in nano and mesoscale is important for making functional materials with desired properties. We have demonstrated the formation of various polymer morphologies such as nanocapsules, two-dimensional (2D) polymers with single monomer thickness, and hollow nanotubular toroidal polymer microrings by covalent self-assembly of rigid, disk-shaped building blocks via irreversible covalent bond formation reactions including thiol-ene photo-addition, olefin metathesis, and amidation with potential applications. We are now focusing our attention on dynamic covalent assembly using reversible covalent bond formation to control the polymer morphology in a reversible manner. Thus, we synthesized a perthioester cucurbit[6]uril (PTE-CB[6]), having 12 protected thiol groups, which can form reversible disulfide bonds upon deprotection of thioester under basic condition. The reactive thiol-CB[6] formed multiple disulfide bonds with each other to produce (i) 2D polymer films spanning over several micrometers in dichloromethane and (ii) polymer nanocapsules with average diameters of 150 nm in methanol. Importantly, we can control and manipulate the morphology of the polymer by simple solvent exchange. The resulting polymers have been characterized by various techniques including SEM, TEM, AFM and DLS. The details of the work will be presented.

Glutathione (GSH) is a tripeptide consisting of glycine, cycsteine and glutamic acid. GSH deficiency in cells contributes to oxidative stress, which plays a key role in aging and the pathogenesis of many diseases such as Alzheimer, Parkinson, diabetes and other ailments. Hence, a glutathione sensor that is able to monitor GSH levels in body fluid could be an important tool for preventing such diseases. This research focuses on the possibility of devising a new mechanism for testing GSH sensible material in saliva that can be used to determine GSH levels. Two main strategies used in the research are molecularly imprinting technology (MIT) and Co2+-imidazole mediated binding complex (Co-MIP). The polymeric matrices obtained using MIT, which are called molecularly imprinted polymers (MIP), can be strong molecular recognition elements able to mimic natural recognition entities such as antibodies and biological receptors. The structure of metal ion and imidazole binding on the other hand is useful for aqueous environments (such as saliva) because of the high stability of the binding structure. For this research, Co-MIP was used for enhancing sensitivity and selectivity of glutathione imprinted polymer (GSH-MIP) to GSH molecules in Saliva. GSH-MIP was successfully synthesized by radical polymerization, and a sensitivity test of GSH-MIP showed promising results for inventing a glutathione sensor. MIP effect was confirmed when the sensitivity of GSH-MIP was compared with non-imprinted polymer. Also, Co-MIP showed highest sensitivity to GSH in physiological condition buffer solution (1X PBS).

Over past two decades, there have been booming research interests in antifouling materials, for their great significance in biomedicine. Zwitterionic materials, especially carboxybetaine (CB)-based materials, have attracted great attention due to their outstanding antifouling properties of resisting proteins, mammalian cells and microbes, as well as the capability of further functionalization.
Despite intense interests in zwitterionic materials for many biomedical applications, there are several challenges to be solved to let the potential of zwitteironic materials fully realized. Firstly, existing zwitterionic materials are fragile and not stretchable. Secondly, hydrophobic elastic materials cannot resist bacterial attachment and zwitterionic materials cannot kill a small amount of attached microbes. Therefore, it is highly desired to have a material integrating all desired properties including excellent antifouling property/biocompatibility to prolong the lifetime of implanted materials, antimicrobial property to eliminate surgical infection and chronic inflammation, and good mechanical properties/stability to avoid the structure failure of the implanted material. Although compression properties of zwitterionic materials can be improved by copolymerization or increasing crosslinking density, a good elasticity cannot be easily obtained due to their high water solubility and high water content.
A new elastic zwitterionic material, pCBMAA-1, was synthesized and characterized. It shows high stability in both acidic and basic condition, as well as reversible switchability between zwitterionic carboxylate form (antifouling) and cationic six-membered ring form (antimicrobial). It is reported for the first time that a single material combines the advantages (elasticity, switchablility, stability, antifouling and antimicrobial properties) while overcomes the disadvantages of both antifouling materials and elastic materials. This study provides a better understanding on relationships among structure, function and stability of zwitterionic materials.

Surfaces containing defined microscale chemical gradients may be important for various applications including the directed transport, separation, and concentration of molecules (including biomolecules). However, formation of microscale chemical gradients in soft-matter surfaces remains challenging. We present a facile method to form micrometer to near-millimeter scale surface chemical gradient in a tertiary amine functionalized polymer brush via a selective quaternization with an alkylating agent. The poly(2-(dimethylamino)ethylmethacrylate) (pDMAEMA) brush is grown on a Si wafer by surface-initiated atom transfer radical polymerization (SI-ATRP) and a microfluidic channel made of polydimethylsiloxane (PDMS) is placed on the brush surface. An alkylating agent solution introduced through the channel diffuses into the permeable PDMS channel wall and intrinsically forms a concentration gradient, which leads to a degree of quaternization of the bottom pDMAEMA brush. The resulting chemical gradient on a polymer brush is quantitatively characterized by confocal Raman spectroscopy. Two different alkylating agents, methyl iodide and benzyl bromide, create different types of chemical gradients of charge and, in the case of benzyl bromide, a capacity for pi-pi interactions. We investigate the effect of the diffusion time and the concentration of the alkylating agent solution for the precise control of the length and the profile shape of the chemical gradient. A charge gradient as narrow as tens of micrometers is achieved by optimizing the process conditions. We will present experimental results showing that diffusion of alkylating agent into the PDMS surrounding the channel is the dominant mechanism for the gradient formation. The benefit of this microfluidic-based selective quaternization technique is that the quaternized brush can be patterned into nearly arbitrary shapes by using differently shaped channels. Two-dimensional brush gradient maps with various patterns are visualized using fluorescence and confocal Raman microscopy. This simple and robust method provides a practical way of creating a narrow gradient of numerous chemical properties.