Versatile Biofunctionalization of Polypeptide-Based Thermosensitive Hydrogels via Click Chemistry
Versatile Biofunctionalization of Polypeptide-Based Thermosensitive Hydrogels via Click Chemistry
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通过点击化学对基于多肽的热敏水凝胶进行多功能生物功能化
DOI：
10.1021/bm3017059
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发表时间：
2013-02-01
影响因子：
6.2
通讯作者：
Chen, Xuesi
中科院分区：
文献类型：
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作者：
Cheng, Yilong;He, Chaoliang;Chen, Xuesi
在这项研究中，我们报道了基于聚（乙二醇）-嵌段聚（γ -丙炔- l-谷氨酸）（PEG-PPLG）的热敏水凝胶。采用C-13核磁共振光谱、DLS光谱和圆二色光谱对溶胶-凝胶相变机理进行了研究。将小鼠成纤维细胞L929细胞包封在水凝胶基质中培养，包封后的细胞在水凝胶基质中具有较高的存活率，表明水凝胶具有良好的细胞相容性。与对照组相比，蛋白酶K的存在加速了体外水凝胶的质量损失。体内生物相容性研究表明，皮下层原位形成的凝胶持续时间约为21天，H&E染色研究表明我们的材料在体内具有可接受的生物相容性。烷基侧基在PEG-PPLG共聚物中的存在使得叠氮化物修饰的生物活性分子（如生物素和半乳糖）可以方便地进一步功能化。生物功能化聚乙二醇多肽嵌段共聚物表现出与亲本共聚物相似的溶胶-凝胶相变。有趣的是，在水凝胶中掺入半乳糖基团可以改善细胞粘附，这可能是由于纤维连接蛋白（FN）在细胞外基质（ECM）中的吸附。由于生物活性材料在生物医学应用中显示出独特的优势，特别是在组织工程和再生医学应用中，我们相信我们的新型功能化热敏水凝胶有潜力成为开发新型生物功能材料的通用平台，例如生物粘合剂和生物反应性水凝胶。
In this study, we report thermosensitive hydrogels based on poly(ethylene glycol)-block-poly(gamma-propargyl-L-glutamate) (PEG-PPLG). C-13 NMR spectra, DLS, and circular dichroism spectra were employed to study the mechanism of the sol-gel phase transition. Mouse fibroblast L929 cells were encapsulated and cultured within the hydrogel matrices, and the encapsulated cells were shown to be highly viable in the gel matrices, suggesting that the hydrogels have excellent cytocompatibilities. The mass loss of the hydrogels in vitro was accelerated by the presence of proteinase K compared to the control group. In vivo biocompatibility studies revealed that the in situ formed gels in the subcutaneous layer last for similar to 21 days, and H&E staining study suggested acceptable biocompatibility of our materials in vivo. The presence of alkynyl side groups in the PEG-PPLG copolymers allowed convenient further functionalization with azide-modified bioactive molecules, such as biotin and galactose. The biofunctionalized PEGpolypeptide block copolymers showed sol-gel phase transitions similar to the parent copolymers. Interestingly, the incorporation of galactose groups into the hydrogels was found to improve cell adhesion, likely due to the adsorption of fibronectin (FN) in cell-extracellular matrix (ECM). Because bioactive materials have shown unique advantages in biomedical applications, especially tissue engineering and regenerative medicine applications, we believe our novel functionalizable thermosensitive hydrogels have potential to serve as a versatile platform for the development of new biofunctional materials, for example, bioadhesive and bioresponsive hydrogels.