紫外聚合缓释Kartogenin PLGA纳米颗粒/水凝胶复合支架修复软骨缺损

关节软骨缺损是常见病、多发病，骨软骨损伤达3000万/年以上。由于在生物支架材料、种子细胞来源、构建组织工程软骨的形式等方面存在各种不足，仍无法得到天然软骨。课题组前期体外使用小分子有机化合物Kartogenin (KGN)成功诱导滑膜源性间充质干细胞成软骨和关节腔内注射KGN有效修复软骨损伤(Arthritis Research & Therapy 2015)，且已构建KGN纳米缓释/紫外聚合水凝胶系统。本项目将缓释KGN水凝胶支架采用紫外点光源照射方式软骨受损处成胶重建受损软骨面；通过吸引自身成体干细胞归巢来进行软骨修复，方法简单安全有效。进一步设计实验阐明软骨修复过程中外源性间充质干细胞使用必要性以及系统阐明软骨修复过程中新生组织分化、发育、成熟及退变全过程。通过研究，课题组完善KGN纳米缓释/水凝胶系统，寻找安全、有效、临床可操作的治疗策略；并为软骨损伤修复提供新的理论依据。

Articular cartilage defect is difficult to be cured so far. Stem cell based cartilage tissue engineering is a promising strategy to regenerate natural hyaline cartilage. However, due to the shortcomings in effective reagents,biological scaffold materials and the way to construct tissue engineering cartilage,cartilage regeneration by tissue engineering remains elusive. This project is expected to be a breakthrough in three aspects. Firstly, we have synthesized small molecule compound Kartogenin (KGN) which is proved to induce synovium-derived mesenchymal stem cells into chondrocytes and have built the sustained-release KGN PLGA nanoparticles; Secondly, we have successfully constructed a hyaluronic acid-based hydrogel scaffold; Thirdly, our team will combine the photoreactive sustained-release KGN PLGA nanoparticle/hydrogel composite scaffold with synovial mesenchymal stem cells to repair cartilage defects. We will assess the quality of regeneration tissue by examining osteochondral structure (cartilage thickness, fill, surface location, bone cartilage interface location, chondrocytes distribution, and boundary), cartilage composition (cellularity, matrix content) and cartilage biomechanical function. A safe, effective strategy to restore cartilage defect might be explored.