功能性仿生润滑剂生物润滑机制及其调控骨关节炎炎症通路的研究

Osteoarthritis (OA), a common orthopaedic disease, which seriously affect the life of the old, is pathologically based on the articular cartilage degeneration, complicated mechanical stress and biology or other factors. However, the explicit pathogenesis of OA remains unknown. This project raises an efficient path to improve or treat OA aiming at cartilage performance reduction resulted in articular cartilage regression, which accelerate OA or even induces other cartilage diseases. In this study, the structural and functional bionics of biological lubrication in cartilage synovial joints has been presented. A set of bottle-brush bionic lubricants, HA as main chain, PAMPS, PMPC as branches have been established. After combining OA specificity drug or polypeptide, the bottle brush bionic lubricant is view to improve lesion cartilage lubricity and also adjust related gene signal path. This project presents a comprehensive study to the morphology characteristics of the bionic lubricant molecular chain conformation in dynamic or static states and its lubricating properties under different friction pair and states, thereby establish the correlation between friction properties and chain conformation, and then illuminate the lubrication mechanism. The impact of bionic lubricant to OA related gene passages have been researched through cytocompatibility evaluated by cartilage functioning cell and arthrosis OA model in vitro. This project is hope to further elucidate OA pathogenesis, provide series syringeability bionic lubricants which can efficaciously improve OA cartilage lubricity, simultaneously treat it in gene level, thus, benefit mass OA patient.

骨关节炎（OA）是常见骨科疾病，严重影响人们尤其是中老年人正常生活。关节软骨退变、复杂应力及生物学因素是其病理基础，具体发病机制尚未明确。项目针对软骨退变与损伤导致润滑性能下降而加速OA进程甚至诱发其他软骨疾病问题，提出对关节滑液生物润滑素进行结构与功能仿生，构建透明质酸为主链，PAMPS和PMPC聚合物为支链并结合OA特异性药物/多肽的瓶刷状仿生润滑剂(BL)，以期改善病变软骨润滑性的同时调控OA相关信号通路，为治疗骨关节炎提供新途径。系统研究BL动静态链构象特征及不同摩擦副、动静态载荷等条件下润滑性能，建立润滑性能与链构象间内在关联，阐明其润滑机理；通过软骨功能细胞评价BL细胞相容性，并结合体内外关节OA模型，研究BL对OA相关因子、蛋白表达影响。该研究有望进一步阐释OA发病机制，提供系列有效改善OA病变软骨润滑性同时从OA发病机制和病理学层次治疗OA的可注射性BL，造福OA疾病患者。

骨关节炎（Osteoarthritis, OA）是最常见的退行性关节致残疾病，研究表明，软骨润滑性能的降低是OA诱发源头，同时对OA病理发展起推动作用。基于润滑性能在OA中的角色，本研究试图通过改善润滑性能实现软骨再生，设计构建了基于天然软骨润滑机理的两种仿生润滑剂。首先重点研究了仿生润滑剂可将OA模型关节软骨的润滑恢复至正常关节软骨水平的润滑性能，探索了恢复软骨润滑性能的作用机理是仿生润滑剂分子因与软骨基质蛋白的强亲和性而组装结合到软骨表面，实现润滑性能的分子机理是水化润滑；随后构建了能模拟OA病理进展中前期、中期和晚期微环境的三维细胞模型，并利用该模型研究了仿生润滑剂的生物相容性及其对不同病变程度OA的影响；最后针对性地将仿生润滑剂作用于早期OA动物模型，基于仿生润滑剂的作用机理和分子机理，OA中软骨的持续性不可逆降解得到有效改善，并最终实现了软骨的再生，从而建立了恢复关节软骨润滑性能与软骨细胞代谢行为及软骨再生之间的关联。此研究为OA的治疗提供了新的可能的策略，并为此从材料设计到细胞模型再到动物模型提供了基础的数据理论支持。