Dual Functionalization of Gelatin for Orthogonal and Dynamic Hydrogel Cross-Linking.
Dual Functionalization of Gelatin for Orthogonal and Dynamic Hydrogel Cross-Linking.
复制标题
明胶的双功能化用于正交和动态水凝胶交联。
DOI：
10.1021/acsbiomaterials.1c00709
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发表时间：
2021-09-13
影响因子：
5.8
通讯作者：
Lin, Chien-Chi
中科院分区：
文献类型：
--
作者：
Kim, Min Hee;Han Nguyen;Chang, Chun-Yi;Lin, Chien-Chi
明胶基水凝胶由于其丰富的支持细胞粘附和基质重塑的生物活性基序而广泛应用于生物医学领域。虽然具有固有的生物活性，但未改性的明胶表现出温度依赖性流变学，并在体温下溶解，使其对于三维（3D）细胞培养不稳定。因此，需要添加化学反应基序，以使明胶基水凝胶具有高度可控的交联动力学和可调的机械性能，这对于3D细胞培养至关重要。本文提供了一系列的方法建立正交交联明胶基水凝胶的动态三维细胞培养。特别是，我们制备了双官能化明胶大分子单体服从顺序，正交共价交联。该材料平台的核心是合成石墨烯官能化明胶（GelNB），其通过正交硫醇-石墨烯点击交联形成共价交联的水凝胶。使用GelNB作为起始材料，我们进一步详细描述了合成对羟基苯乙酸（HPA）二聚敏感的明胶大分子单体的方法（即，GelNB-HPA）和腙键合（即，GelNB-CH）用于按需基质硬化。最后，我们概述了用于合成能够通过硼酸酯键合调节水凝胶应力松弛的明胶大分子单体的方案（即，GelNB-BA）。这些正交化学的组合提供了广泛的基于明胶的水凝胶作为组织工程和再生医学应用中的仿生基质。
Gelatin based hydrogels are widely used in biomedical fields owing to its abundance of bioactive motifs that support cell adhesion and matrix remodeling. While inherently bioactive, unmodified gelatin exhibits temperature-dependent rheology and solubilizes at body temperature, making it unstable for three-dimensional (3D) cell culture. Therefore, the addition of chemically reactive motifs is required to render gelatin-based hydrogels with highly controllable crosslinking kinetics and tunable mechanical properties that are critical for 3D cell culture. This article provides a series of methods toward establishing orthogonally crosslinked gelatin-based hydrogels for dynamic 3D cell culture. In particular, we prepared dually functionalized gelatin macromers amenable for sequential, orthogonal covalent crosslinking. Central to this material platform is the synthesis of norbornene-functionalized gelatin (GelNB), which forms covalently crosslinked hydrogels via orthogonal thiol-norbornene click crosslinking. Using GelNB as the starting material, we further detail the methods for synthesizing gelatin macromers susceptible to hydroxyphenylacetic acid (HPA) dimerization (i.e., GelNB-HPA) and hydrazone bonding (i.e., GelNB-CH) for on-demand matrix stiffening. Finally, we outline the protocol for synthesizing a gelatin macromer capable of adjusting hydrogel stress-relaxation via boronate ester bonding (i.e., GelNB-BA). The combinations of these orthogonal chemistries affords a wide range of gelatin based hydrogels as biomimetic matrices in tissue engineering and regenerative medicine applications.
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影响因子：
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作者：
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