用于软骨下骨重塑的骨修复材料的制备及其抑制软骨组织血管化与成骨趋化的作用机理研究

Osteoarthritis (OA) is the most common degenerative joint disease, while so far there are no effective clinical therapies and surgical methods against osteoarthritis. Recent studies indicate that OA may be induced by subchondral bone and calcified layer, therefore subchondral bone reconstruction probably is the breakthrough for OA treatment. Based on former studies on OA pathogenesis and cartilage repair tissue engineering materials, this project focuses on the research of repairing subchondral bone, prepares composited bone repair materials with features of inhibiting bone vascularization and osteogenesis, and studies its inhibition mechanism of bone vascularization and osteogenesis. Our work is aimed at exploring the impact of subchondral bone reconstruction on the treatment of OA, and their interaction with each other from the perspectives of materials science and biology. The research project is expected to have important academic contribution to the study of the impact of subchondral bone on OA pathogenesis, the research of subchondral bone reconstruction on delaying the articular cartilage degeneration, and the design and preparation of injectable multi-micro-nano self-solidified bone repair materials in order to diversify theories of OA treatment.

骨关节炎(Osteoarthritis，OA)是最常见的退行性关节疾病，目前尚无有效的针对骨性关节炎的临床治疗药物和手术措施。近年来研究表明OA的发生可能源于软骨下骨和钙化层结构，因此通过调节软骨下骨重建治疗骨关节炎可能是目前骨关节炎治疗最具希望的突破点。本项目将结合当前骨性关节炎的最新发生机制研究及其软骨修复组织工程材料研究，重点以修复软骨下骨为研究对象，基于一定机械强度的成熟骨修复材料内构建具备抑制骨组织血管化及其成骨趋化功能的复合修复体；研究复合材料对抑制软骨下骨组织血管生成及其钙沉积行为方面的作用机制。从材料学、生物学方面探索建立软骨下骨对关节炎影响的评价体系及其他们之间存在的内在相互影响规律。项目预期成果对于研究软骨下骨在骨关节炎发病机制中的地位，调控软骨下骨重塑对于延缓关节软骨退变的作用机理；建立微创型软骨－软骨下骨修复材料的设计与制备理论有重要的学术与应用价值。

关节软骨细胞外基质( ECM) 微环境调控着促血管生成因子与抗血管生成因子的动态平衡，OA 病理性新生血管的形成正是这一内在平衡机制打破的体现。那么在重塑关节软骨下骨的过程中如何调节血管化与成骨化的进程将是该课题需要解决的关键问题。该项目研究工作主要围绕软骨下骨重塑及其关节腔相关炎症调控开展工作。设计生物医用的功能化材料体系；利用离子掺杂及有机复合有效实现材料的功能化改性,解决临床应用问题。目前基本确定了活性离子在血管化及其炎症微环境调控的生物学效应，这为以后的研究工作奠定了l理论基础；首次确认了溴离子对软骨细胞的调控作用。通过该项目的实施，基本确定了以鹿茸为生物模型，构建功能性材料体系并通过合适的临床适应症进行验证的研究思路。