可注射双交联水凝胶支架的可控聚合及其与神经干细胞的适配性研究

Currently, tissue engineering regenerative medicine and cell transplantation based therapy remains an important challenge, emphasizing the need to design of cell-compatible scaffolds. In this project, novel injectable hydrogel scaffolds are planed to development via in situ sol-gel phase transition,which allow the inclusion of living cells during gelation. These composite hydrogel scaffolds are consisting of protein and polysaccharide,polymerizing by both covalent and noncovalent dual crosslinking.The based materials are naturally derived proteins and polysaccharides,including of collagen, gelatin, fibroin, alginate, herprin and hyaluronic acid. These scaffolds are modelled on the natural extracellular matrix (ECM) of central nervous system via modulation of optimized parameters, including of base materials, crosslinkers, ploymerization strategies and degree. The ECM-inspired scaffolds are highly oriented micro-porous hydrogels, providing both controllable degradability and stiffness of substrate that is suitable for nervous soft tissue. Furthermore, in vitro evaluation of cell-compatibility of these hydrogel scaffolds are investigated with the interaction of neural stem cells (NSCs) on their two and three-dimension biointerface. The NSCs behaviors of viability, proliferation, adhesion and migration are tested, in order to indentify the appropriate of hydrogel scaffolds for NSCs delivery vehicles. This project is highly beneficial for development of novel in-situ dual crosslinked polymerization to design and engineer injectable scaffolds, which is cell-compatible biomaterials for basic and clinical applications in cell therapy, tissue engineering for central nervous system regeneration.

构建适用细胞移植的支架材料，是当前细胞治疗、组织工程修复领域中富有挑战性的研究前沿。本项研究采用天然高分子蛋白质（如：胶原、明胶、丝素蛋白等）和多糖（如：透明质酸、海藻酸钠、肝素等）为基质材料，制备新型可注射、复合水凝胶细胞支架，研究其载运活细胞时的原位凝胶化，共价-非共价键双交联的聚合方法。基于中枢神经细胞外基质特点，通过化学组分、交联剂、聚合方式及聚合程度等因素优化，进行仿生设计，调控水凝胶支架形成：高度有序的微孔结构、可控的降解速率、适配神经软组织的生物力学特征。探讨体外神经干细胞在水凝胶支架材料所构筑的二维及三维生物界面上特异性的相互作用规律，阐明神经干细胞的存活、粘附、增殖、定向迁移的行为与水凝胶支架间的适配性机制。本项研究为构建可注射型水凝胶的提供新型原位双交联的聚合方法，为制备具有临床应用价值的细胞治疗、中枢神经组织修复的水凝胶支架奠定理论研究基础。

构建适用细胞移植的支架材料，是当前细胞治疗、组织工程修复领域中富有挑战性的研究前沿。本项研究采用天然高分子蛋白质（如：丝素蛋白等）和多糖（如：透明质酸等）为基质材料，制备新型可注射、复合水凝胶细胞支架，研究其载运活细胞时的原位凝胶化，共价-非共价键双交联的聚合方法。阐明神经干细胞与水凝胶支架间的适配性机制。此外，本项研究构筑多功能纳米生物材料体系，研究其对恶性肿瘤细胞等的生物特异性识别、显像、诊断与治疗。本项课题为设计构筑适配细胞的生物材料及其应用提供基础研究数据。. 本项课题执行期间发表学术期刊论文11篇，其中SCI国际权威学术期刊9篇，包括国际SCI顶级学术期刊（Top Journal）论文：Small 1篇，ACS Macro Letter 1篇，ACS Appl. Mater. Interfaces 1篇，Chemistry -A European Journal 1篇，Carbon 1篇，Journal of Materials Chemistry B 2篇，受邀为《中国科学•化学》撰写综述论文2篇，授权国家发明专利7项。