Molecular Weight Influence on Gelatin Gels: Structure,Enthalpy and Rheology

Summary: This paper deals with the gelation properties of gelatins with various molecular weights. The samples are 4 different extracts from limed bones. We investigated firstly the structural properties: the helix amounts by optical rotation measurements and the enthalpy of helix formation and melting, with the same thermal protocols and for various concentrations. Comparison between the two methods allowed deriving the enthalpy of helix-coil transition and melting. Rheology was performed under the same conditions with a stress controlled rheometer working with a fixed, very small, strain during gel formation, maturation and melting. Correlation between all the measurements confirms the existence of the master curve for storage modulus versus gelatin concentration for all samples investigated.     

Mechanical Properties and Failure Behavior of Physically Assembled Triblock Copolymer Gels with Varying Midblock Length

Mechanical properties including the failure behavior of physically assembled gels or physical gels are governed by their network structure. To investigate such behavior, we consider a physical gel system consisting of poly(styrene)‐poly(isoprene)‐poly(styrene)[PS‐PI‐PS] in mineral oil. In these gels, the endblock (PS) molecular weights are not significantly different, whereas, the midblock (PI) molecular weight has been varied such that we can access gels with and without midblock entanglement. Small angle X‐ray scattering data reveals that the gels are composed of collapsed PS aggregates connected by PI chains. The gelation temperature has been found to be a function of the endblock concentration. Tensile tests display stretch‐rate dependent modulus at high strain for the gels with midblock entanglement. Creep failure behavior has also been found to be influenced by the entanglement. Fracture experiments with predefined cracks show that the energy release rate scales linearly with the crack‐tip velocity for all gels considered here. In addition, increase of midblock chain length resulted in higher viscous dissipation leading to a higher energy release rate. The results provide an insight into how midblock entanglement can possibly affect the mechanical properties of physically assembled triblock copolymer gels in a midblock selective solvent. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 1014–1026     

二乙烯基砜交联的可德胶化学水凝胶的制备与表征

以二乙烯基砜(DVS)作为交联剂通过亲电加成反应制备了可德胶化学水凝胶。采用傅里叶变换红外光谱(FT-IR)、扫描电子显微镜(SEM)和质构分析手段表征了所得凝胶的结构与性能,并对其形貌、溶胀率以及水凝胶的力学性质与制备条件的关系进行了研究。结果表明:所得凝胶网络结构较为致密均匀,溶胀率依赖于交联度。可德胶化学水凝胶的强度和韧性可以通过DVS的用量、可德胶的浓度和碱溶液的浓度进行调控。     

Injectable in situ Physically and Chemically Crosslinkable Gellan Hydrogel

An injectable, in situ physically and chemically crosslinkable gellan hydrogel is synthesized via gellan thiolation. The thiolation does not alter the gellan's unique 3‐D conformation, but leads to a lower phase transition temperature under physiological conditions and stable chemical crosslinking. The synthesis and hydrogels are characterized by ¹H NMR, FT‐IR, CD, or rheology measurements. The injectability and the tissue culture cell viability is also tested. The thiolated gellan hydrogel exhibits merits, such as ease for injection, quick gelation, lower gelling temperature, stable structure, and nontoxicity, which make it promising in biomedicine and bioengineering as an injectable hydrogel.

     

明胶膜的制备及其交联性能的研究

探讨了溶剂、温度及pH值对明胶膜性能的影响，并以甲醛和戊二醛为交联剂，采用溶液交联和蒸汽交联两种方法对明胶膜进行交联改性。研究结果表明：相对于溶液交联，甲醛蒸汽交联所得膜的拉伸强度从25MPa上升到42MPa，戊二醛交联的膜的拉伸强度从15MPa上升到40MPa，而溶胀率和溶出率均有所下降，蒸汽交联的膜的性能优于溶液交联的膜。     

Dielectric behaviour of Gelatin solutions and Gels

 Sol and Gel state properties of aqueous gelatin solutions of concentrations 4%, 6%, 8% and 10% (w/v) have been investigated through dielectric relaxation studies done at various temperatures in the range T=20–60 °C carried out over a frequency range f=20 Hz–10 MHz and no relaxation of any nature was observed. The sharp transition observed at the gelation temperature T _gel provided an excellent matching with the same measured through differential scanning calorimetry (DSC). The capacitance (C _p) values above f=100 kHz became increasingly negative as the gel was melted to the sol state. However, in the gel state C _p was found to be almost independent of temperature for frequencies above 100 kHz. At frequencies lower than 10 kHz, C _p measured was ∼10⁵ F, implying pronounced interfacial polarization either due to electro-chemical reaction or because of ions getting trapped at some interface within the bulk. Received: 10 February 1997 Accepted: 2 September 1997     

甲基丙烯酰胺基明胶水凝胶研究进展

甲基丙烯酰胺基明胶(GelMA)水凝胶的制备及其在生物医学领域的应用是最近十几年的研究热点。GelMA水凝胶因其独特的光致交联特性,可以加工成不同形貌的水凝胶支架材料,同时,因其具有可控的力学性能、降解性能,以及优秀的生物相容性,已成为具有广泛应用前景的生物高分子聚合物材料。本文主要介绍了GelMA水凝胶在止血材料、创伤敷料、组织工程支架、药物控释、骨缺损修复等领域的研究进展。     

明胶/胶原改性的研究进展

明胶/胶原因其优良的理化性质和生物学性能而在生物材料、食品包装等方面得到了广泛的应用,但其热稳定性差、机械强度低、水汽阻隔性能差等缺点限制了它的应用,因此在很多应用场合需要对明胶/胶原进行交联改性处理。本文主要综述了近年来国内外对明胶/胶原进行共混和化学交联改性以及物理改性的研究进展,并对其作用效果进行了分析。     

Designing Gelatin Based Blood Compatible Materials with Hydrophilic and Hydrophobic Macromolecular Chains

Polymer matrices based on poly 2-hydroxyethyl methacrylate (PHEMA) have emerged as promising materials for developing applications in biomedical and tissue engineering fields. The major criteria of a material to be used as a support matrix in tissue engineering application rests on its biocompatible, hydrophilic, and mechanically strong nature. Although a great deal of research efforts have been put into designing such materials, achieving these properties together for such a material still remains a challenge. Thus, by a judicious combination of natural and synthetic polymers, such as gelatin and copolymers of PHEMA and PAN, respectively, it has been attempted to synthesize a polymer material by redox polymerization method. The prepared polymer matrix was characterized by FTIR, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) techniques. The prepared polymeric biomaterials were assessed for their water sorption potential under varying experimental conditions such as chemical composition, pH, and temperature of the swelling bath. The diffusion mechanism of transport of water molecules arising due to solvent–polymer interaction was analyzed to predict the behavior of continuously relaxing macromolecular chains. The in vitro blood compatibility of the prepared polymeric materials was determined by methods such as blood clot formation, platelet adhesion, percent hemolysis assay, and protein–adsorption on the surface of the prepared biomaterials.     

Shear‐reversibly Crosslinked Alginate Hydrogels for Tissue Engineering

Injectable delivery vehicles in tissue engineering are often required for successful tissue formation in a minimally invasive manner. Shear‐reversibly crosslinked hydrogels, which can recover gel structures from shear‐induced breakdown, can be useful as an injectable, because gels can flow as a liquid when injected but re‐gel once placed in the body. In this study, injectable and shear‐reversible alginate hydrogels were prepared by combination crosslinking using cell‐crosslinking and ionic crosslinking techniques. The addition of a small quantity of calcium ions decreased the number of cells that were required to form cell‐crosslinked hydrogels without changing the shear reversibility of the system. The physical properties and gelation behavior of the gels were dependent on the concentration of both the cells and the calcium ions. We found that gels crosslinked by combination crosslinking methods were effective to engineer cartilage tissues in vivo. Using both ionic and cell‐crosslinking methods to control the gelation behavior may allow the design of novel injectable systems that can be used to deliver cells and other therapeutics for minimally invasive therapy, including tissue engineering.

     

Mechanically tough and recoverable hydrogels via dual physical crosslinkings

Development of functional tough hydrogels with new network structures and energy dissipation mechanisms has great promise for many applications. Here, a new type of physical hydrogel crosslinked by hydrophobic association and hydrogen bonds was synthesized by a facile micellar copolymerization of hydrophobic methyl acrylate (MA) monomers and hydrophilic N-hydroxyethyl acrylamide (HEAA) monomers in the presence of Tween80 micelles. Strong hydrophobic association between inner MA and Tween80 and hydrogen bonds between external polyHEAA and Tween80 provide two distinct crosslinkers to construct mechanically tough and recoverable network. Mechanical properties of polyHEAA-MA@Tween80 hydrogels strongly depended on network components (HEAA, MA; Tween80 concentrations). At optimal conditions, the hydrogels can achieve fracture stress of 700 kPa, fracture strain of 1687 mm/mm, elastic modulus of 195 kPa, and tearing energy of 1598 J/m². Due to the reversible nature of physical interactions, polyHEAA-MA@Tween80 hydrogels can achieve fast stiffness/toughness recovery of 60%/33% without any external stimuli and resting time at room temperature. This work demonstrates a new design strategy to fabricate a new a single-network hydrogel with high mechanical and self-recovery properties by incorporating both hydrophobic association and hydrogen bonds in the network, which may provide alternative viewpoint for the design of multifunctional tough hydrogels. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 1294–1305     

非水介质中明胶水凝胶电场驱动行为的研究

研究了明胶水凝胶在绝缘硅油中的电场响应行为。结果表明,在硅油中,明胶水凝胶在外加高压直流电场作用下可发生运动,其运动由转动和平动两部分组成。存在一个运动所需的最小阈值电场,只有外加电场在此阈值以上时,才可观察到水凝胶明显的运动。水凝胶的运动速度随外加电场的增大而增大,其运动可通过外加电场的大小来调控。由硅油很稳定且在电场中会电解,因此避免了传统电场驱动水凝胶在水介质中响应时不可避免的电解缺点,为建立一种新的电响应凝毅然驱动方式提供了可能。     

Enzyme‐Free Quinone Crosslinking Reaction for Proteins: A Macromolecular Characterization Study Using Gelatin

To mimic the quinone hardening of extracellular proteins in invertebrates, we investigated an enzyme‐free crosslinking of gelatin by HQ in a neutral aqueous phase. The mixture was rapidly transformed to a yellowish brown, thermally and mechanically stable hydrogel in the presence of a simple copper(II) salt. A dehydrated thin film made of the mixture was flexible, tough, and showed a large ultimate breaking force. Physicochemical examination of the gel suggested that the basic amino acid residues (lysine, hydroxylysine, and histidine) of the protein were modified by the quinone ring to form 2–6 crosslinks per protein. The enzyme‐free crosslinking reaction is discussed with consideration of a copper(II) ion‐catalyzed oxidation of HQ and the hydroquinone/protein adducts.

     

Cellular Response to Reagent‐Free Electron‐Irradiated Gelatin Hydrogels

As a biomaterial, it is well established that gelatin exhibits low cytotoxicity and can promote cellular growth. However, to circumvent the potential toxicity of chemical crosslinkers, reagent‐free crosslinking methods such as electron irradiation are highly desirable. While high energy irradiation has been shown to exhibit precise control over the degree of crosslinking, these hydrogels have not been thoroughly investigated for biocompatibility and degradability. Here, NIH 3T3 murine fibroblasts are seeded onto irradiated gelatin hydrogels to examine the hydrogel's influence on cellular viability and morphology. The average projected area of cells seeded onto the hydrogels increases with irradiation dose, which correlates with an increase in the hydrogel's shear modulus up to 10 kPa. Cells on these hydrogels are highly viable and exhibits normal cell cycles, particularly when compared to those grown on glutaraldehyde crosslinked gelatin hydrogels. However, proliferation is reduced on both types of crosslinked samples. To mimic the response of the hydrogels in physiological conditions, degradability is monitored in simulated body fluid to reveal strongly dose‐dependent degradation times. Overall, given the low cytotoxicity, influence on cellular morphology and variability in degradation times of the electron irradiated gelatin hydrogels, there is significant potential for application in areas ranging from regenerative medicine to mechanobiology.

     

医用高分子水凝胶的设计与合成

作为一类重要的医用功能材料,高分子水凝胶可望在药物控释、软骨支架构建、活性细胞封装等方面获得广泛应用。综述了基于化学交联和物理交联的有关水凝胶的设计与合成方法,重点介绍了通过自由基共聚反应、结构互补基团间化学反应形成的化学交联水凝胶以及通过荷电相反离子问相互作用、两亲性嵌段或接枝共聚物疏水缔合、结晶与氢键相互作用形成的物理交联水凝胶。     

Study of Complex Coacervation of Gelatin A and Sodium Alginate for Microencapsulation of Olive Oil

Complex coacervation of gelatin A and sodium alginate was carried out to obtain the maximum coacervate yield. Turbidity and coacervate yield (%) measurements were carried out to support the ratio of the two polymers and pH that produced maximum coacervation. The optimum ratio between gelatin A-sodium alginate and pH to form the maximum coacervate complex was found to be 3.5:1 and 3.5–3.8, respectively. Olive oil microencapsulation was carried out at the optimized ratio and pH. Microcapsules were crosslinked by using glutaraldehyde. Scanning electron microscopy studies confirmed the formation of free flowing spherical microcapsules of different sizes. The size of microcapsules increased with the increase in the concentration of the polymer. The encapsulation efficiency and the release rates of olive oil were dependent on the amount of crosslinker, oil loading and polymer concentration. Thermogravimetric study revealed improvement of thermal stability with crosslinking. Fourier Transform Infrared Spectroscopy study showed that there was no significant interaction between olive oil and gelatin-alginate complex.     

Crosslinked Silk Fibroin/Gelatin/Hyaluronan Blends as Scaffolds for Cell-Based Tissue Engineering

3D porous scaffolds fabricated from binary and ternary blends of silk fibroin (SF), gelatin (G), and hyaluronan (HA) and crosslinked by the carbodiimide coupling reaction were developed. Water-stable scaffolds can be obtained after crosslinking, and the SFG and SFGHA samples were stable in cell culture medium up to 10 days. The presence of HA in the scaffolds with appropriate crosslinking conditions greatly enhanced the swellability. The microarchitecture of the freeze-dried scaffolds showed high porosity and interconnectivity. In particular, the pore size was significantly larger with an addition of HA. Biological activities of NIH/3T3 fibroblasts seeded on SFG and SFGHA scaffolds revealed that both scaffolds were able to support cell adhesion and proliferation of a 7-day culture. Furthermore, cell penetration into the scaffolds can be observed due to the interconnected porous structure of the scaffolds and the presence of bioactive materials which could attract the cells and support cell functions. The higher cell number was noticed in the SFGHA samples, possibly due to the HA component and the larger pore size which could improve the microenvironment for fibroblast adhesion, proliferation, and motility. The developed scaffolds from ternary blends showed potential in their application as 3D cell culture substrates in fibroblast-based tissue engineering.     

Design and Fabrication of Highly Stretchable and Tough Hydrogels

Abstract

Stretchable and tough hydrogels have attracted a lot of attention due to their great potential in applications such as wound healing, drug delivery, tissue culture, etc. They can also be paired with electronic components to create artificial skin, wearable electronics, and patches. To promote the development of more hydrogels, we will summarize methods and materials that have been used to develop these gels, and then we will compare the performance of these gels in an aim to guide the future development of gels for superior performance, especially for specific applications.