模拟ECM蛋白/多肽细胞粘附功能的尼龙3聚合物及类似物研究

ECM蛋白/多肽具有细胞粘附功能，在组织工程的研究和实践中被广泛使用, 但其也有价格昂贵、制备困难、易被蛋白酶水解、功能受表面接枝方法影响的显著缺点。本课题拟以尼龙3聚合物(β-氨基酸聚合物)及其类似物(α-氨基酸聚合物)模拟ECM蛋白/多肽的细胞粘附功能，通过细胞粘附、溶血和细胞毒性研究对这两类聚合物进行综合评价并进行结构和功能优化。申请人在前期研究中初步验证这一思路是可行的(J. Am. Chem. Soc. 2013, 135: 16296; Biomacromolecules 2012, 13: 1100)，预期获得具有优异细胞粘附功能、有潜力应用于组织工程的氨基酸聚合物。通过系统性研究两类氨基酸聚合物的细胞粘附功能、机理，以及分析氨基酸骨架结构对细胞粘附功能的影响，深入对于细胞粘附功能氨基酸聚合物的基础理论研究，并为发现可替代ECM蛋白/多肽的细胞粘附功能氨基酸聚合物奠定基础。

Extra cellular matrix (ECM) proteins/peptides, for example fibronectin and RGD peptide, are cell adhesive and are widely used in the research and clinical application of tissue engineering. However, ECM proteins/peptides have their innate shortcomings including, expensive, difficult to prepare, susceptible to proteolysis, and their cell adhesive function’s dependence on surface tethering method. The research in the project will mimic the cell adhesive function of ECM proteins/peptides using nylon-3 polymers (poly-β-amino acid) and their analogous polymers (poly-α-amino acid). The overall performance of these polymers will be evaluated based on their cell adhesive function, their hemolysis and their cytotoxicity, which supports the optimization of these polymers’ structure and cell adhesive function. Preliminary studies by the applicant verified the feasibility of this research approach (J. Am. Chem. Soc. 2013, 135: 16296; Biomacromolecules 2012, 13: 1100), and we expect to obtain poly-amino acid that possess outstanding cell adhesive function and have potential to be used in tissue engineering. The in-depth and fundamental understanding of cell adhesive poly-amino acid will be obtained via systematic study on cell adhesive function and mechanism of these two types of poly-amino acid, and analysis on the relationship between amino acid backbone and resulting polymers’ cell adhesive function. These studies also support the finding of optimum cell adhesive poly-amino acid that can substitute ECM proteins/peptides and have potential in tissue engineering applications.