光偶联反应可控构筑双网络（微）水凝胶

Artificial construction of bionic 3D extracellular matrix (ECM) has great biomedical significance. Hydrogels are the biomaterials that show the highest similarity to natural ECM. In consideration of the weak mechanical strength of single-network crosslinking hydrogels, dual-network crosslinking hydrogels are developed to make up the shortcomings. However, their construction methods are cumbersome, uncontrollable and lack of biocompatibility. In view of the above situation, this project proposes the following works based on our previous construction of single-network ECM hydrogel by “photo-induced coupling reaction” of biological macromolecules. 1) To achieve in situ construction of high-strength hydrogel in one step, biomacromolecules that can synchronously photo-release thiol and aldehyde are prepared, based on which dual “photo-induced coupling reaction” is implemented to build interconnected dual-network 3D structure; 2) A microgel ECM system with wide range of strength regulation and excellent cytocompatiblity is proposed by combining microfluidic technology with “photo-induced coupling reaction” which shows unique advantages of convenient operation, low toxicity and spatiotemporal controllability; 3) Light energy can be transformed to mechanical signal via in situ light controlled mechanical strength of microgel, thus a construction technique of 3D biomimetic microgel ECM for studying the fate of stem cells can be developed. The smooth implementation of this project can overcome many shortcomings of traditional methods and is expected to promote dual-network high-strength hydrogel towards biomedical applications.

人工构建仿生3D细胞外基质（ECM）具有重大生物医学意义。水凝胶是最为接近天然ECM的生物材料。考虑到传统的单网络交联结构的水凝胶机械强度太弱，新近发展的双网络水凝胶虽能弥补以上缺点，但是构建方法多步繁琐、生物相容性差并且不可控。针对以上现状，本项目在“光偶联反应”构建单网络ECM水凝胶的工作基础上，提出开展以下工作：1）制备具有光剪切同步释放巯基和醛基的生物大分子，实施双重“光偶联反应”交联形成两个网络相关联的三维结构，实现高强度水凝胶的一步光原位构建；2）结合“光偶联反应”特有的操作便捷、低毒与时空可控等特征，提出利用微流控技术构建强度广泛可调、高细胞存活率的双网络微凝胶ECM体系；3）基于光原位调控微凝胶强度能够实现光能转变为机械信号的独特优势，发展用于研究干细胞分化命运的3D仿生微凝胶ECM构建技术。以上研究工作克服了传统方法的诸多缺陷并有望推动双网络高强度水凝胶迈向生物医学应用。

人工构建仿生3D细胞外基质（ECM）具有重大生物医学意义。水凝胶是最为接近天然ECM的生物材料。考虑到传统的单网络交联结构的水凝胶机械强度太弱，新近发展的双网络水凝胶虽能弥补以上缺点，但是构建方法多步繁琐、生物相容性差并且不可控。针对以上现状，本项目在“光偶联反应”构建单网络ECM水凝胶的工作基础上，合成具有同步光剪切释放多官能度的生物大分子并实施双重“光偶联反应”，发展生物友好、时空可控及操作便捷性的高强度双网络水凝胶的一步法光原位构筑技术；进一步结合机械加工技术，建立高细胞存活率、强度精确光可控的双网络微凝胶构建方法；最终通过双重“光偶联反应”的源头创新，拓展高强度双网络水凝胶技术在生物医学领域的实际应用，在肋软骨和关节软骨缺损修复等组织工程与再生医学应用上取得优异的成果。本项目创新研究结果发表本项目标注的高质量SCI学术论文7篇，包括Science Advances 1篇，Angew. Chem. Int. Ed. 1篇，Biomaterials 1篇等。