促腱骨愈合的材料学因素及调控机制研究

韧带、肌腱由于其独特的组成与结构而缺乏自愈能力，韧带、肌腱损伤通常需要手术重建且康复周期较长，而腱骨愈合是实现成功重建的关键之一。韧带起止点在细胞类型、基质成分、组织结构与力学性能等方面都存在梯度变化特征，其修复再生涉及多种材料学因素。本项目拟针对目前临床广泛应用的自体肌腱移植物和具有理想重建潜能的组织诱导性人工韧带移植物，设计并制备多种形式的促腱骨愈合材料，包括可注射钙磷陶瓷、负载钙磷陶瓷电纺膜和具有定向排列特征的胶原纤维支架材料，通过系统的制备工艺与性能表征明确其构效关系；通过体外培养筛选促腱骨愈合的关键材料学因素，进一步通过体内实验验证材料的促腱骨愈合效果，并优化其应用方式；在分子和亚分子水平设计材料与细胞的相互作用，探讨胶原特定序列和结构特征、钙磷陶瓷理化参数对于细胞行为的影响及调控方法，初步阐述材料与细胞作用的分子机制，为进一步指导促腱骨愈合材料的优化升级和临床应用奠定基础。

Ligament and tendon (LT) have very limited self-healing capacity owing to their unique components and structure. Generally, the LT injuries need surgery to regenerate or repair, and long rehabilitation duration. The ligament/tendon-bone (LT-B) healing is vital to the successful regeneration. The ligament enthesis exhibits gradations in cell phenotype, matrix composition, tissue organization and mechanical properties, involving multiple material factors during the regeneration. In this program, two different ligament implants, including autologous tendon transplantation which is widely applied in clinic and tissue inducing artificial ligament implant which is potential in the future, are considered for designing and preparing of LT-B healing implants. Injectable calcium phosphate ceramic, calcium phosphate ceramic-loaded electro-spinning membrane and collagen scaffold based on aligned filaments will be developed and optimized to achieve specific structure-performance relationships. The key material factors will be screened and filtered via in vitro cell culture. The accelerating effect of LT-B healing implants will be tested and verified in vivo, and the application methods will be optimized at the same time. The influence of material factors on cell will be studied on both molecule and sub-molecule levels, including collagen with specific primary and secondary structures and calcium phosphate ceramic with certain physicochemical parameters. Meanwhile, the regulate approaches and control methods on cell behaviors via material factors will be expected. Finally, the preliminary molecule mechanism will be stated, which will direct the further optimization and update of LT-B healing implants and solidify the foundation for potential clinical application.