基于类硫酸软骨素梯度聚合物凝胶仿生构建骨-软骨界面的研究

Chondroitin sulfate (CS) is one of ubiquitous glycosaminoglycan, which plays a key role in regulating the physiological activities in organism. Particularly, CS performs a significant promotion capacity of repairing bone and cartilage interface defects. According to the principle of bionics, this application started from the design and fabrication of CS analogue based gradient polymer gels. Combined with induced mineralization and cell loading technology, integrated construction of functional osteochondral defect repairing materials were integratively constructed. Through the multiple synergetic effects of chemical composites and gradient structures, the physiological behaviors of targeted cell were effectively regulated. Subsequently, further optimizing and utilizing the functionalities of hydrogel materials were carried out to regulate the gradient mineralization process in order to realize the interface sealing of repairing material. Finally, functional gradient structures between bone and cartilage interface in organisms were entirely duplicated and the restorative effects of CS analogue-based gradient polymer gels were also evaluated in vivo. Based on this research, it can contribute to elucidating the regulatory mechanism of CS chemical composition and structure on cell spreading, proliferation and differentiation, as well as the repairing and regeneration mechanism of bone and cartilage interface. It has important researching significance and potential application value for the development and optimization of the functional properties of bone and cartilage interface repairing materials.

硫酸软骨素是一种对生物体生理活动起到重要调节作用的糖胺聚糖，特别对修复生物体内骨-软骨界面缺损，表现出显著的促进作用。本申请拟利用生物仿生学原理，从设计和制备类硫酸软骨素梯度聚合物凝胶材料出发，结合诱导矿化和细胞负载技术，一体化构建功能性骨-软骨界面缺损修复材料。通过类硫酸软骨素聚合物凝胶化学组成和结构梯度的多重协同效应，实现凝胶材料对目标细胞生理功能行为的有效调控；进一步优化和利用凝胶材料组成和结构的功能性调控梯度矿化过程，实现修复材料的界面密封功能；最终，整体复制生物体内骨-软骨界面功能梯度结构，评价类硫酸软骨素聚合物梯度凝胶修复材料对骨-软骨界面缺损的修复效果。基于此项研究，有助于阐明硫酸软骨素化学组成和结构对细胞铺展、增殖和分化等生理行为的调节机理，以及骨-软骨缺损修复和再生骨-软骨界面的作用机制。同时，对开发和优化骨-软骨界面修复材料的功能性，具有重要的研究意义和潜在应用价值。

硫酸软骨素是一种对生物体生理活动起到重要调节作用的糖胺聚糖，特别对修复生物体内骨-软骨界面缺损，表现出显著的促进作用。本项目研究采用生物仿生学策略，以天然硫酸软骨素的化学组成及其在软骨-骨界面处的分布、作用方式和功效等方面，设计了一系列带有硫酸和氨基葡萄糖结构的类硫酸软骨素聚合物基功能材料，包括可用于吸附低密度脂蛋白的聚合物磁性微球、用于骨-软骨界面修复的梯度凝胶材料、用于细胞标记和骨髓间充质干细胞诱导分化的碳量子点材料等，初步实现了以类硫酸软骨素聚合物化学组成和结构梯度的多重协同效应，来调控目标细胞诸如铺展、增殖和分化等生理功能行为的设计。另外，基于相似的仿生合成研究思路，在本项研究中也合成了透明质酸仿生启迪的功能聚合物，配合培养基的细胞生长微环境，用于有效调控骨髓间充质干细胞的成骨和成软骨分化。基于本项研究，有助于阐明硫酸软骨素化学组成和结构对细胞行为的调节机理，有助于建立仿生功能聚合物对骨-软骨缺损修复和再生骨-软骨界面修复的作用机制。因此，对基于类硫酸软骨素功能聚合物材料设计、开发和应用，具有重要的研究意义和潜在应用价值。