用于软骨及软骨下骨缺损修复的双层超分子水凝胶研究

The scaffolds for osteochondral defect repair in regenerative medicine still need to be improved, including the following three aspects: how to efficiently support two different tissues repair in the same scaffold simultaneously; how to fill defects of different shapes with scaffolds simply but efficiently; how to achieve a strong combination of two new tissue interfaces through scaffold design. In response to the above problems, we design a new self-bonding injectable double-layer supramolecular hydrogel. The two layers of hydrogel in this scaffold can achieve multiple stimulatory factor loadings by host-guest binding and charge attraction to ensure directing the differentiation of bone marrow mesenchymal stem cells (MSCs). By utilizing the injectable property of pre-formed hydrogels, the two layers of hydrogel in the scaffold can be separately cultured in vitro to further ensure the following tissue repair efficiency in vivo, and then the cultured two layers of hydrogel are sequentially injected into the defect site to complete efficient filling of defects. At last, based on the same reversible host-guest combination, the scaffold can achieve a self-bonding in the interface between the two layers of hydrogel after injection, thereby promoting the interfacial integration of the subsequent regenerative cartilage and subchondral bone. This study may provide new ideas for the scaffold design to repair two or more kinds of connected tissues.

再生医学中软骨及软骨下骨缺损修复的支架材料仍有待改进，主要包括以下三个方面：如何在同一支架中同时支持两种不同组织的高效修复；如何实现支架对不同形状缺损的简单有效填充；如何通过支架设计实现两种新生组织界面的牢固结合。针对上述问题，本项目设计了新型自粘结可注射双层超分子水凝胶。该支架中的两层水凝胶可各自通过主客体结合和电荷吸引完成对不同刺激因子的多重负载，以保证对不同区域内骨髓间充质干细胞分化的定向引导。利用水凝胶中的弱主客体结合带来的二次注射成型性质，可实现支架中的两层水凝胶先行在体外分别进行分化培养以进一步保证体内的组织修复效率，再将培养后的两层水凝胶依次注射到缺损部位，完成对各种不同形状缺损的高效填充。最后，两层水凝胶中均存在的相同可逆主客体结合可实现注射后两层水凝胶界面的自粘附，进而促进新生软骨和软骨下骨的界面结合。本项目研究结果可为两种或多种相连组织一体化修复支架设计提供新思路。

再生医学中软骨及软骨下骨缺损修复的支架材料仍有待改进，主要包括以下三个方面：如何在同一支架中同时支持两种不同组织的高效修复；如何实现支架对不同形状缺损的简单有效填充；如何通过支架设计实现两种新生组织界面的牢固结合。课题组基于前期关于动态水凝胶设计及其在组织工程中的应用研究基础，设计了一种新型自粘结可注射双层超分子水凝胶。本项目执行期间，已全部所设计的软骨修复水凝胶及骨修复水凝胶的制备及性能表征，并通过动物实验分别证明了上述两种水凝胶的组织修复能力。随后，基于上述两种水凝胶的优选制备方案，课题组已完成可用于软骨及软骨下骨缺损修复的双层水凝胶材料制备及性能表征，证实了通过双层水凝胶的自粘附性设计，可实现两种水凝胶界面的紧密结合，可为软骨及软骨下骨新生组织的有效连接提供保障，同时已开展动物实验进行修复性能测试。本项目的实施证实超分子动态水凝胶在两种或多种相连组织一体化修复支架修复方向具有良好的潜力，对多组织修复的支架材料研发具有重要的启示意义。课题组将在以后的工作中进一步优化该支架材料的设计制备，继续推动其在软骨及软骨下骨缺损修复的临床应用发展。截止目前，依托本项目的实施，已发表SCI论文9篇，培养硕士毕业生2名。