一体化取向纳米纤维膜经FAK/PI3K促进肌腱愈合的作用及机制研究

肌腱粘连是手外伤常见并发症，治疗棘手；现有生物材料膜可阻隔粘连，但疗效不佳，影响肌腱愈合。申请人前期利用聚乳酸构建一体化电纺纳米纤维防粘连膜，疗效提高，但仍不能促进肌腱愈合；深入研究发现肌腱损伤处募集骨髓间充质干细胞（BMSCs）源性肌腱细胞参与腱愈合，且取向纳米纤维具有促进该类细胞生成作用，预实验显示此过程与Akt及下游Caspase9表达相关。结合文献，整合素β1/FAK经PI3K/Akt介导BMSCs的分化，故假设：取向纳米纤维膜可经整合素β1/FAK/PI3K/Akt介导BMSCs源性肌腱细胞生成、促进腱愈合，并阻隔粘连。为验证假设，本项目拟构建一体化取向纳米纤维防粘连膜，阐明该膜取向结构通过整合素β1激活FAK再经PI3K/Akt介导BMSCs源性肌腱细胞生成机制；并利用Leghorn鸡肌腱粘连模型验证该膜促腱愈合和防粘连的体内效果，为应用防粘连材料促进肌腱愈合提供新的思路。

Tendon adhesion is a common complication of hand injury, which is difficult to treat. The current biomaterial membranes can prevent adhesion, to a certain extent, however, affects the strength of repaired tendon. The applicant innovated integrative Poly-L-lactide electrospun nanofiber anti-adhesion membrane previously which improved the effectiveness, but could not promote tendon healing; Further research found that tendon healing was related to the BMSCs derived tendon cells in injured area, and the oriented nanofiber structure can promote the formation of such cells; meanwhile, this process was regulated by Akt and its downstream caspase 9, and the differentiation is regulated by integrin β1 / FAK via PI3K / Akt. Therefore, the project assumes that the oriented nanofiber anti-adhesion membrane can mediate the differentiation of BMSCs derived tendon cells and promote tendon healing through integrin β 1 / FAK / PI3K / Akt signal pathway. This project aims to apply electrospun technology to build the integrative oriented nanofiber anti-adhesion membrane, clarify the mechanism of differentiation of BMSCs derived tendon cells mediated by the oriented nanostructure through integrin β1 / FAK / PI3K / Akt pathway, and use Leghorn chicken to build tendon adhesion model for in vivo verification, so as to provide a new approach for the construction and application of anti-adhesion materials to promote tendon healing.