光解离超分子水凝胶的构建及其在干细胞培养中的应用

In recent years, the supramocular chemistry based on the macrocyclic compounds as the hosts has attracted great interests, since it can be used to construct a series of functional supramolecular complexes or assemblies, which exhibit greatly potential applications in some advanced fields such as biological medicines and chemsensors. In this proposal, we will fabricate the photo-dissociated supramolecular hydrogels via the photo-controlled association and disassociation interation between azobenzene derivatives as the guests and the macrocyclic compounds such as cyclodextrin (CD), cucurbituril (CB) and pillararene (P(n)A) as the hosts. The disassociated degree and process of supramolecular hydrogel could be well controlled by light, which will overcome the issue of the non-controlling degradation of the conventional hydrogels. We will design a series of photo-dissociated supramolecular hydrogels, which could be used for cultivation of stem cells. We will choose the best hydrogel for in vitro expansion of stem cells after the systematical evaluation of these hydrogels, and then build up three-dimensional supramolecular hydrogel supported culture systems where the cultivation process could be well-controlled, and the cells are very easily harvest. These will make a great breakthrough on stem cell therapy which is hampered for the insufficient numbers of stem cells.

近年来，以大环化合物为主体的超分子化学引起了研究者的广泛兴趣，因为其可以通过主客体之间的包结络合作用构建一系列功能性的超分子包结物或组装体，并在生物医药、化学传感等前沿领域显示出巨大的应用前景。在本申请中，我们将利用大环化合物(环糊精、葫芦脲和柱芳烃)为主体分子，以其和偶氮苯为客体分子之间的光可控包结络合和解包结络合的相互作用，构建光可控解离的超分子水凝胶。根据水凝胶应用的需要有效地对光解离程度和光解离过程进行调控，解决传统可降解水凝胶的降解过程和程度不可控等问题。我们将通过对水凝胶分子结构的设计，构建一系列特异性的光解离超分子水凝胶，使得这类水凝胶可被应用于干细胞的体外扩增。通过对光可控解离水凝胶的系统评价，进一步筛选出最适合于干细胞体外扩增的超分子水凝胶，进而建立培养过程可监控、细胞收获便利的干细胞三维扩增体系，以加速体外扩增干细胞临床转化进程，解决目前干细胞治疗细胞来源不足的问题。

本项目基本上按照项目计划书实施，我们通过主客体相互作用等构建了一系列功能性响应性水凝胶，为构建此类水凝胶材料提供了方法上的借鉴；通过对该类水凝胶的结构和性能系统的评价，揭示了该类材料的结构与性能之间的构效关系，尤其通过超分子水凝胶的结构设计制备了具有较好力学强度同时又具备可加工性、自愈合以及优异的生物相容性的超分子水凝胶。我们重点探究了该类水凝胶的应用，尤其在干细胞体外扩增、骨组织修复以及软组织修复中的应用。通过构建有机/无机杂化水凝胶或双网络水凝胶等，建立了干细胞体外三维扩增体系；通过构建生物相容性好和优异的力学性能功能性水凝胶，不仅促进了干细胞有效地粘附、扩散和增殖，同时实现了骨组织修复；通过构建具有自修复和生物相容性的超分子水凝胶，其可被潜在应用于视网膜等软组织的修复。在此项目资助下，我们共发表影响因子大于5的论文25篇，其中包括Biomaterials, Biomater. Sci., ACS Appl. Mater. Interfaces, ACS Macro Lett., Biomacromolecules, Angew. Chem. Int. Ed., 以及Mater.Horizon等，培养了博士生2名，硕士生7名；参加国内外学术会议10多次，并在相关会议上做邀请报告和口头报告等。