功能化PVA/PAAm仿生关节盘靶向调控髁突软骨干细胞修复骨关节炎软骨破坏的机制研究

To achieve the reversal of condylar cartilage destruction and regeneration in temporal mandibular joint osteoarthritis (TMJOA), restoring the functional structure of the joint disc and starting the repair function of important target cells are the two most critical factors. The functional PVA/PAAm bionic joint disc prepared in the early stage can achieve the functional reconstruction of joint structure and meanwhile regulate the biological function of cells by releasing drugs. Some latest research have confirmed that the condylar fibrocartilage stem cells (FCSCs) is an important potential seed cell type for cartilage repair in TMJOA, yet the mechanism of their function during OA has not been systemically clarified. Previous studies have confirmed that TGF-β/Smad, an important signaling pathway for the regulation of TMJOA, is a target pathway for the regulation of FCSCs in the reparation of TMJOA, as well as plays an important role in the stem cells differentiation. Accordingly, we first proposed to regulate FCSCs cell and reverse TMJOA cartilage destruction based on functional PVA/PAAm bionic articular disc through TGF-β/Smad pathway. Based on the basis of functional PVA/PAAm bionic joint plate slow-release function, our project will focus on the analysis of TGF-β/Smad on FCSCs cell fate regulatory mechanism, the dynamic monitoring of the function of target cells repairing mechanism; and then realize the outcome of reversing the destruction of TMJOA cartilage by PVA/PAAm bionic functional materials while explore the related molecular mechanism at the same time. All these scientific questions might bring new insight for future clinical treatment of TMJOA.

颞下颌关节骨关节炎（TMJOA）治疗中，恢复关节盘结构并启动重要靶细胞的修复机能是实现软骨破坏逆转再生的两个关键因素。髁突软骨干细胞（FCSCs）是TMJOA中软骨修复重要的功能细胞；TGF-β/Smad通路在TMJOA中参与FCSCs的机能调控。但如何有效利用TGF-β/Smad通路，充分动员FCSCs参与软骨损伤修复成为目前亟需突破的瓶颈。申请人制备的功能化PVA/PAAm仿生关节盘能够实现关节盘功能重建，同时可以缓释药物调控细胞生物学机能。据此，本研究拟在分析TGF-β/Smad对FCSCs细胞命运调控机制的基础上，利用PVA/PAAm仿生关节盘的功能缓释，调控FCSCs修复TMJOA软骨破坏；并动态监测靶细胞修复机能的实现过程，探讨功能化材料修复TMJOA软骨破坏的分子机制。为发掘利用功能化人工关节盘治疗TMJOA的临床新策略以及寻求TMJOA治疗潜在新方法提供理论基础和数据支持。

颞下颌关节骨关节炎（TMJOA）治疗中，恢复关节盘结构是一切治疗的前提和基础。多项研究证实：在关节盘正常结构尚未恢复的情况下，各类 TMJOA 治疗干预手段均难以有效实现髁突软骨破坏的修复再生。构建一种具有功能替代的仿生颞下颌关节盘适配局部细胞与微环境，是突破当前盘损伤修复难题的有效途径。本项目围绕如何系统解析和仿生重建受损关节盘开展以下研究：一、通过关节盘胞外基质的高清解析，明确关节盘结构、成分及力学性质；二、运用3D打印、脱细胞技术等结合高分子加强，完成脱细胞高性能颞下颌关节盘构建；三、通过动物模型探索与改良，完成仿生颞下颌关节盘的体内效能性评价；四、应用多种影像学评估手段及数据分析、统计分析方法，回顾相关临床数据，指导临床实践。本研究的开展将形成颞下颌关节盘“精准构建”的新思路、新材料与新技术，为临床上颞下颌关节盘置换与再生的治疗新策略提供理论基础和技术支撑。