State Key Laboratory of Materials-Oriented Chemical Engineering, College of Food Science and Light Industry, Nanjing Tech University, Nanjing 211816, China.
School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China.
Int J Biol Macromol. 2020 Jan 1;142:332-344. doi: 10.1016/j.ijbiomac.2019.09.104. Epub 2019 Oct 5.
While peptide-directed scaffolds now serve as well-established platforms for biomimetic three-dimensional (3D) extracellular matrices (ECM), challenges still remain for chondrogenesis through direct mediation of stem cells. Here, biocompatible poly (γ-glutamic acid) (γ-PGA) hydrogels with robust mechanical properties were developed based on methacrylate-γ-PGA (γ-PGA-GMA) and cysteamine functionalized γ-PGA (γ-PGA-SH) for cartilage regeneration. The γ-PGA hydrogels demonstrated good self-crosslinking property as well as tunability through conjugation between active thiol groups of γ-PGA-SH and methacrylate moieties of γ-PGA-GMA. The mechanical property, porous structure, swelling, and degradation process of the hydrogels could be controlled by adjusting modified γ-PGA polymers component. The rheological behavior and compression test of γ-PGA hydrogels illustrated a wide processing range in addition to superb mechanical properties. These γ-PGA hydrogels showed excellent elasticity as well as toughness, withstanding more than 70% of mechanical strain. Meanwhile, the stress modulus of γ-PGA hydrogels could be up to 749 kPa. We also studied γ-PGA hydrogels as scaffolds for the 3D culture and chondrogenesis differentiation of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. In a rabbit auricular cartilage defect model, BMSCs-laden hydrogel effectively promoted chondrogenesis. Based on these findings, biomimetic γ-PGA-based hydrogels hold promising application as favorable scaffold biomaterials for cartilage tissue regeneration.
虽然肽导向支架现在已经成为仿生三维（3D）细胞外基质（ECM）的成熟平台，但通过干细胞的直接介导，仍然存在着软骨生成的挑战。在这里，基于甲基丙烯酰基-γ-聚谷氨酸（γ-PGA-GMA）和半胱胺功能化γ-聚谷氨酸（γ-PGA-SH），开发了具有良好生物相容性的具有强机械性能的聚（γ-谷氨酸）（γ-PGA）水凝胶，用于软骨再生。γ-PGA 水凝胶表现出良好的自交联性能，并且通过γ-PGA-SH 的活性巯基基团与γ-PGA-GMA 的甲基丙烯酰基之间的共轭，可实现可调性。通过调节改性γ-PGA 聚合物成分，可以控制水凝胶的机械性能、多孔结构、溶胀和降解过程。γ-PGA 水凝胶的流变行为和压缩试验表明，除了具有极好的机械性能外，还具有很宽的加工范围。这些 γ-PGA 水凝胶表现出极好的弹性和韧性，可承受超过 70%的机械应变。同时，γ-PGA 水凝胶的应力模量可达 749kPa。我们还研究了 γ-PGA 水凝胶作为支架，用于兔骨髓间充质干细胞（BMSCs）的 3D 培养和软骨生成分化。在兔耳软骨缺损模型中，负载 BMSCs 的水凝胶有效地促进了软骨生成。基于这些发现，仿生 γ-PGA 基水凝胶有望作为软骨组织再生的有利支架生物材料得到应用。
