pH‐Sensitive Mechanical Properties of Elastin‐Based Hydrogels

Ionizable amino acids in protein‐based hydrogels can confer pH‐responsive behavior. Because elastin‐like polypeptides (ELPs) have an established sequence and can crosslink to form hydrogels, they are an ideal system for creating pH‐sensitive materials. This study examines different parameters that might affect pH‐sensitive behavior and characterizes the mechanical and physical properties between pH 3 and 11 of three ELP‐based crosslinked hydrogels. The first finding is that varying the amount of crosslinker affects the overall stiffness and resilience of the hydrogels but does not strongly affect water content, swelling ratio, or pH sensitivity. Second, the choice of two popular tag sequences, which vary in histidine and aspartic acid content, does not have a strong effect on pH‐sensitive properties. Last, selectively blocking lysine and tyrosine residues through acetylation significantly decreases the pH‐sensitive zeta potential. Acetylated hydrogels also demonstrate different behavior at low pH values with reduced swelling, reduced water content, and higher stiffness. Overall, this work demonstrates that ELP hydrogels with ionizable groups are promising materials for environmentally‐responsive applications such as drug delivery, tissue engineering, and microfluidics.     

Tough superabsorbent poly(acrylic acid) nanocomposite physical hydrogels fabricated by a dually cross-linked single network strategy

In this work, we report a facile method for the preparation of tough and highly stretchable physical hydrogels by dual cross-linking composed of vinyl-hybrid silica nanoparticles(VSNPs) as multivalent covalent cross-linking and hydrogen bonding as physical cross-linking. Poly(acrylic acid) nanocomposite physical hydrogels(NCP gels) are obtained without adding any organic chemical cross-linkers. When the content of VSNPs is 0.7 wt%(relative to the monomer), the NCP gels exhibit good mechanical properties(fracture strength = 370 k Pa, elongation at break = 2200%) and a high swelling capacity in both deionized water(2300 g/g) and saline(220 g/g). Meanwhile, the NCP gels have good recovery ability.     

Tandem modular protein-based hydrogels constructed using a novel two-component approach

Leucine zipper sequences have been widely used to engineer protein-based hydrogels for biomedical applications. Previously, we have used this method to engineer tandem modular protein-based hydrogels as a step toward developing extracellular matrix-mimetic hydrogels. However, the spontaneous self-association of leucine zipper sequences in solution has made it challenging to express and purify tandem modular proteins carrying leucine zipper under native conditions. To obviate this problem, here we report a novel two-component approach to engineer tandem modular protein-based hydrogels. This methodology makes use of two complementary leucine zipper sequences (CCE and CCK), which do not self-associate but self-assemble into heterodimeric coiled-coils at neutral pH, as functional groups to drive the self-assembly of protein hydrogels. The two protein components are bifunctional and trifunctional tandem modular proteins carrying the leucine zipper functional groups. We found that the two proteins carrying CCE or CCK can be expressed and purified under native conditions with high yield. Upon mixing, the aqueous solution of the two proteins readily forms a transparent hydrogel. The resultant hydrogel can undergo reversible sol-gel transitions as a function of temperature, and shows much improved erosion properties. This method provides a new approach to tune the topology and physical properties of the protein hydrogels via genetic engineering, and opens the possibility to systematically explore the use of large native extracellular proteins to engineer extracellular matrix-mimetic hydrogels.     

Hofmeister效应辅助的蛋白质基水凝胶应变传感器

以酪蛋白酸钠和明胶为原料, 通过简单的在硫酸铵溶液中浸泡的方法, 借助Hofmeister效应制备了一种强韧导电的酪蛋白酸钠/明胶水凝胶, 克服了蛋白质基水凝胶柔软、 易碎的问题. 测试结果表明, 该水凝胶具有优异的机械性能, 最大拉伸应力为3.55 MPa, 最大拉伸应变为1375%; 水凝胶的最大电导率为0.0954 S/cm, 导电灵敏因子为0.53. 用该水凝胶制备的传感器对不同大小及不同速率的应变均具有分辨能力, 能够监测人体不同部位的运动, 且传感器的信号传输具有稳定性和准确性, 表明该水凝胶是监测人体健康和运动的理想材料. 该水凝胶还具有良好的形状记忆性能. 这一策略为制备全天然蛋白质基水凝胶开辟了新的思路, 扩展了水凝胶在生物医学和电子传感等相关领域的应用前景.     

Mechanical and Adhesive Properties of Ploy(ethylene glycerol) Diacrylate Based Hydrogels Plasticized with PEG and Glycerol

Using polyethylene glycol(PEG) or glycerol as the plasticizer, we synthesized the hydrogels from poly(ethylene glycol) diacrylate(PEGDA), polyvinylpyrrolidone(PVP) and poly(vinyl alcohol)(PVA) under UV radiation. The effects of different plasticizers on the mechanical properties and adhesion properties of the hydrogels were investigated. The results show that the plasticizer can improve the elongation and peeling force. The most pronounced changes in the tensile property of the hydrogels are due to the addition of glycerol followed by PEG, the lower the plasticizer's molecular weight, the greater its effect. The maximum peeling force is 0.317 or 0.257 N with PEG or glycerol as plasticizer, respectively, and their adhesion properties are due to the formation of hydrogen bonds.     

Evaluation of the degree of cross-linking of cellulose-based superabsorbent hydrogels: a comparison between different techniques

Three different techniques have been applied to the evaluation of the degree of cross-linking of superabsorbent cellulose-based hydrogels obtained from water solutions of carboxymethylcellulose sodium salt (CMCNa) and hydroxyethylcellulose (HEC), chemically cross-linked with divinyl sulfone. These polyelectrolyte hydrogels are biodegradable and have the same sorption capacity as acrylate-based superabsorbents on the market. A ¹³C solid state NMR analysis was carried out on dry samples of hydrogel to obtain the degree of cross-linking, an important parameter that affects the swelling and mechanical properties of a hydrogel. Dynamic mechanical analysis was performed during the hydrogel cross-linking using a parallel plate rheometer under oscillatory deformations in order to monitor the evolution of the hydrogel viscoelastic properties during the synthesis. The value of |G*| and the slope of the stress-deformation ratio plots from uniaxial compression tests were used to evaluate the elastically effective degree of cross-linking according to classical rubber elasticity theory. Moreover, a dynamic mechanical analysis was carried out on cross-linked hydrogels at different degrees of swelling in order to investigate the influence of the swelling on the mechanical properties and the application of rubber elasticity theory to swollen hydrogels.     

Amorphous Silk Fibroin Nanofiber Hydrogels with Enhanced Mechanical Properties

Silk fibroin (SF) hydrogels have been engineered as universal substrates for various tissue regenerations and drug delivery. Although different physical and chemical crosslinking strategies are developed to form SF hydrogels with suitable performances, a significant gap remains to match specific requirements of various tissues. Here, amorphous SF nanofibers with more tyrosine residues outside the surfaces are used to replace traditional SF. Under the same crosslinking conditions, the use of amorphous SF nanofibers results in tougher properties, four times higher stiffness than that from traditional SF solutions. Unlike previous SF hydrogels, the SF nanofiber hydrogels show high tunability in wide modulus range of 0.6–160 kPa under low SF concentrations (below 5 wt%), showing improved mechanical match with various soft tissues. Better stability and cytocompatibility are also achieved, further confirming the superiority of the hydrogels as the tissue substrates. Therefore, a feasible strategy is developed to optimize the performances of SF hydrogel via tuning the nano‐structural state in aqueous solutions, which will enrich SF‐based hydrogel family in future.     

Ultrahigh-water-content supramolecular hydrogels exhibiting multistimuli responsiveness

Hydrogels are three-dimensional networked materials that are similar to soft biological tissues and have highly variable mechanical properties, making them increasingly important in a variety of biomedical and industrial applications. Herein we report the preparation of extremely high water content hydrogels (up to 99.7% water by weight) driven by strong host-guest complexation with cucurbit[8]uril (CB[8]). Cellulosic derivatives and commodity polymers such as poly(vinyl alcohol) were modified with strongly binding guests for CB[8] ternary complex formation (K(eq) = 10(12) M(-2)). When these polymers were mixed in the presence of CB[8], whereby the overall solid content was 90% cellulosic, a lightly colored, transparent hydrogel was formed instantaneously. The supramolecular nature of these hydrogels affords them with highly tunable mechanical properties, and the dynamics of the CB[8] ternary complex cross-links allows for rapid self-healing of the materials after damage caused by deformation. Moreover, these hydrogels display responsivity to a multitude of external stimuli, including temperature, chemical potential, and competing guests. These materials are easily processed, and the simplicity of their preparation, their availability from inexpensive renewable resources, and the tunability of their properties are distinguishing features for many important water-based applications.     

Application Properties of Stimuli-Responsive Polyglycerol Hydrogels

Transient state swelling behavior and swelling kinetics of novel stimuli-responsive polyglycerol hydrogels were studied at 293, 310 and 333 K. Depending on temperature, Fickian or anomalous diffusion behavior was observed. Mechanical properties of the hydrogels in the swollen and dry states were investigated and the average molecular weight between crosslinks was calculated. To assess the potential for biodegradation of hydrogels, initial swelling behavior in phosphate buffered saline (PBS) solution and mass loss profiles as a function of degradation time were investigated over a period of 30 days. All swelling behavior, mechanical properties and degradations were clearly affected by the degree of cross-linking. The hydrophilicity and biodegradability of polyglycerol hydrogels make them suitable for pharmaceutical, biomedical and biotechnological applications. They could potentially serve as a substitute for common fossil-based hydrogels such as poly(ethylene glycol) and poly(vinyl alcohol) hydrogels.     

Bentonite Reinforced Tough Composite Hydrogels as Potential Artificial Articular Cartilage

Novel tough composite hydrogels were prepared from inorganic bentonite(IB), polyvinyl alcohol(PVA) and polyethylene glycol(PEG) by means of a freeze-thaw technique, during which IB acted as multifunctional physically crosslinking junction and a filler to bridge the 3D network hydrogel; while the physical adsorption between IB and the polymer chains served as sacrificial bonds and increased the energy dissipation efficiency. The effects of different content of IB(w_IB) on the morphological, thermal, swelling, and mechanical properties of the hydrogels were investigated. It was found that the added IB promoted the material crosslinking and stability, and the mechanical properties of the hydrogels were significantly improved with increasing w_IB. The highest tensile stress of the hydrogel was achieved(1.1 MPa) when w_IBwas 5%. The synthesized hydrogels with high mechanical strength and low friction coefficient are potential candidate materials for artificial cartilage.     

聚(N-异丙基丙烯酰胺)/聚丙烯酰胺无机/有机互穿网络水凝胶的制备及表征

通过紫外引发聚合方法制备了无机交联的聚(N-异丙基丙烯酰胺)(PNIPAAm)/有机交联的聚丙烯酰胺(PAAm)互穿网络(IPN)水凝胶.利用FTIR和SEM分别表征了凝胶的化学结构和内部形态;测定了凝胶在高温(50℃)时的退溶胀性能;利用DMA和DSC分别研究了凝胶的储能模量随温度的变化及热相转变行为.研究表明,该IPN凝胶具有温度敏感性;与未互穿的无机交联PNIPAAm凝胶相比,IPN凝胶具有多孔的网络结构和超快的响应速率,如10min内失去90%的水;其储能模量增加了3～4倍,相转变行为变弱,而最低临界溶解温度(LCST)提高了1.4℃.     

Strategy for selective chemical cross-linking of tyrosine and lysine residues

Chemical cross-linking of proteins combined with mass spectral analysis is a powerful technique that can be utilized to yield protein structural information, such as the spatial arrangement of multi-protein complexes or the folding of monomeric proteins. The succinimidyl ester cross-linking reagents are commonly used to cross-link primary amine-containing amino acids (N-terminus and lysine). However, in this study they were used to react with tyrosines as well, which allowed for the formation of cross-links between two primary amines, one primary amine and one tyrosine, or two tyrosines. This result is extremely important to the chemical cross-linking community for two reasons: (1) all possible cross-linked residues must be considered when analyzing data from these experiments to generate correct distance constraints and structural information, and (2) utilizing the versatility of these cross-linking reagents allows more information content to be generated from a single cross-linking reagent, which may increase the number of cross-links obtained in the experiment. Herein, we study the reactivity of the succinimidyl ester labeling and cross-linking reagents with angiotensin I and oxidized insulin beta-chain. Using the succinimidyl acetate labeling reagent, the reactivity of the N-terminus was found to be greater than either lysine or tyrosine. However, a selectivity of the cross-linking reagent was observed for either tyrosine or lysine depending on the pH of the reaction solution. In acidic pH, it was observed that tyrosine was more reactive, while in alkaline pH lysine was more reactive. Exploiting this selectivity predominantly N-terminus-tyrosine or tyrosine-tyrosine cross-links were favored at acidic pH, while N-terminus-tyrosine or tyrosine-lysine cross-links were favored at alkaline pH.     

会变形的水凝胶

本实验是关于可变形水凝胶的制备及其复杂形变的设计和调控的新创综合实验。首先,利用自由基聚合交联法制备含有聚丙烯酸钠(PNaAAc)的聚乙烯基吡咯烷酮-聚丙烯酰胺(PVP-PAAm)水凝胶。该凝胶具有优良的力学性能,其中PNaAAc可与Fe3+等金属离子络合,从而增加水凝胶的交联密度,降低其溶胀程度。使用离子转移印花技术和新开发的离子墨水打印技术在凝胶单面或双面不同位置引入Fe3+交联,改变水凝胶局部表面的交联密度和溶胀性能。处理后的凝胶样品在溶胀或去溶胀时可发生由一维到二维、二维到三维以及简单三维到复杂三维的复杂可控形变。     

TA of pval hydrogel cross-linked by chemical and eb irradiation process used as artificial articular cartilage

Hydrogels, in general, can be used as a compliant surface in prosthesis of human synovial joints due to their biocompatible characteristics. In this work, different hydrogels were prepared from two aqueous solutions of PVAL (15 and 20 mass/mass%) by chemical reactions using citric acid as a cross-linking agent and by electron beam (EB) irradiation with doses from 25 to 100 kGy. The hydrogels were evaluated by their mechanical properties through indentation creep test, thermal properties by differential scanning calorimetry (DSC), and also equilibrium water content (EWC). This revised version was published online in August 2006 with corrections to the Cover Date.     

Mechanical and transport properties of the poly(ethylene oxide)-poly(acrylic acid) double network hydrogel from molecular dynamic simulations

We used atomistic molecular dynamics (MD) simulations to investigate the mechanical and transport properties of the PEO-PAA double network (DN) hydrogel with 76 wt % water content. By analyzing the pair correlation functions for polymer-water pairs and for ion-water pairs and the solvent accessible surface area, we found that the solvation of polymer and ion in the DN hydrogel is enhanced in comparison with both PEO and PAA single network (SN) hydrogels. The effective mesh size of this DN hydrogel is smaller than that of the SN hydrogels with the same water content and the same molecular weight between the cross-linking points (Mc). Applying uniaxial extensions, we obtained the stress-strain curves for the hydrogels. This shows that the DN hydrogel has a sudden increase of stress above approximately 100% strain, much higher than the sum of the stresses of the two SN hydrogels at the same strain. This arises because PEO has a smaller Mc value than PAA, so that the PEO in the DN reaches fully stretched out at 100% strain that corresponds to 260% strain in the PEO SN (beyond this point, the bond stretching and the angle bending increase dramatically). We also calculated the diffusion coefficients of solutes such as D-glucose and ascorbic acid in the hydrogels, where we find that the diffusion coefficients of those solutes in the DN hydrogel are 60% of that in the PEO SN and 40% of that in the PAA SN due to its smaller effective mesh size.     

Blood compatibility of novel poly(gamma-glutamic acid)/polyvinyl alcohol hydrogels

Sodium poly(gamma-glutamic acid) (PGA), a water-soluble and biodegradable polypeptide, was reacted with polyvinyl alcohol (PVA) to form hydrogel without any chemical treatment. The gelation occurred probably due to physical cross-linking of polymer chains by interpenetrating hydrogen bonding. From the results of thermal analysis, PGA/PVA exhibited better thermal stability than native PVA. Although the swelling ratio decreased with the increase of PGA content, however, the water resistance and retention were improved. The tensile strength of the PGA/PVA hydrogel membranes was about 15-30% lower than that of the native PVA, whereas the elongation was increased 2.0-2.6 times. The amount of protein adsorbed and platelets adhered on the PGA/PVA membranes were significantly curtailed with increasing PGA content, thereby showing improved blood compatibility. The as-fabricated hydrogels were proven to be non-cytotoxic evaluated in vitro by L-929 fibroblast incubation. Overall results demonstrate that the non-cytotoxic PGA/PVA hydrogels, due to better water resistance, mechanical properties and blood compatibility could be very promising candidates for blood-contacting medical devices.     

纳米复合模板水凝胶的制备及其性能

以非离子表面活性剂聚氧乙烯(20)鲸蜡醇醚(Brij58)为模板, 采用自由基聚合制备得到聚(N-异丙基丙烯酰胺)/Brij58/粘土纳米复合模板水凝胶(PLH). 相比于传统纳米复合水凝胶, PLH水凝胶力学性能与亲水性明显改善. 场发射扫描电镜(FESEM)结果表明: Brij58的引入导致传统纳米复合水凝胶的孔洞数量增加, 孔与孔相互贯穿, 大孔结构更加规整, 大孔之间由众多小孔连接. 拉伸应力-应变、储能模量和溶胀动力学研究结果表明, 断裂应力、断裂负载和断裂伸长率随Brij58含量的增加呈先增加后降低的趋势, 然而水凝胶储能模量与最大溶胀度随Brij58含量的增加而增加. 同时, 表面接触角结果表明: 由于Brij58的模板作用和Brij58同粘土之间的吸附作用, 使PLH水凝胶表面接触角先增大后减小.     

Microstructured polyacrylamide hydrogels made with hydrophobic nanoparticles

Poly(methyl methacrylate) nanosize particles, made by microemulsion polymerization, were dispersed in an acrylamide aqueous solution, which was polymerized in the presence of a cross-linking agent to yield microstructured hydrogels. The kinetics of swelling and the mechanical properties of these hydrogels were investigated as a function of concentration of particles. The microstructured hydrogels exhibit higher equilibrium swelling and larger Young modulus than conventional (that is, without particles) polyacrylamide hydrogel. The morphology of the microstructured hydrogels was examined by transmission electron microscopy.     

Preparation of interpenetrating polymer network composed of poly(ethylene glycol) and poly(acrylamide) hydrogels as a support of enzyme immobilization

Poly(ethylene glycol)(PEG)‐based interpenetrating polymeric network (IPN) hydrogels were prepared for the application of enzyme immobilization. Poly(acrylamide)(PAAm) was chosen as the other network of IPN hydrogel and different concentration of PAAm networks were incorporated inside the PEG hydrogel to improve the mechanical strength and provide functional groups that covalently bind the enzyme. Formation of IPN hydrogels was confirmed by observing the weight per cent gain of hydrogel after incorporation of PAAm network and by attenuated total reflectance/Fourier transform infrared (ATR/FTIR) analysis. Synthesis of IPN hydrogels with higher PAAm content produced more crosslinked hydrogels with lower water content (WC), smaller M_c and mesh size, which resulted in enhanced mechanical properties compared to the PEG hydrogel. The IPN hydrogels exhibited tensile strength between 0.2 and 1.2 MPa while retaining high levels of hydration (70–81% water). For enzyme immobilization, glucose oxidase (GOX) was immobilized to PEG and IPN hydrogel beads. Enzyme activity studies revealed that although all the hydrogels initially had similar enzymatic activity, enzyme‐immobilizing PEG hydrogels lost most of the enzymatic activity within 2 days due to enzyme leaching while IPN hydrogels maintained a maximum 80% of the initial enzymatic activity over a week due to the covalent linkage between the enzyme and amine groups of PAAm. Copyright © 2008 John Wiley & Sons, Ltd.     

Mechanically Strong Janus Poly(N-isopropylacrylamide)/Graphene Oxide Hydrogels as Thermo-responsive Soft Robots

Simple preparation of stimuli-responsive hydrogels with good mechanical properties and mild stimuliresponsiveness is essential for their applications as smart soft robots.Mechanically strong Janus poly(Nisopropylacrylamide)/graphene oxide (PNIPAM/GO) nanocomposite hydrogels with stimuli-responsive bending behaviors are prepared through a simple one-step method by using molds made of a Teflon plate and a glass plate.Residual oxygen in the air bubbles on the Teflon plate surface affects the polymerization and hence the cross-linking density,leading to the different swelling/deswelling rates of the two sides of the gels.Therefore,the hydrogels exhibit bending/unbending behaviors upon heating/cooling in water.The incorporation of GO nanosheets dramatically enhances the mechanical properties of Janus hydrogels.Meanwhile,the photo-responsive property of the GO nanosheets also imparts the hydrogels with remotecontrollable deformation under IR irradiation.The application of the Janus PNIPAM/GO hydrogels as thermo-responsive grippers is demonstrated.