Micropattern Silk Fibroin Film Facilitates Tendon Repair and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the 21/FAK/PI3K/AKT Signaling Pathway .

Background: Tendon injuries are common clinical disorders. Due to the limited regeneration ability of tendons, tissue engineering technology is often used as an adjuvant treatment. This study explored the molecular pathways underlying micropattern SF film-regulated TSPC propensity and their repairing effects to highlight the application value of micropattern SF films.

Methods: First, we characterized the physical properties of the micropattern SF films and explored their repairing effects on the injured tendons . Then, we seeded TSPCs on SF films and determined the micropattern SF film-induced gene expression and activation of signaling pathways in TSPCs through high-throughput RNA sequencing and proteomics assays.

Results: The results of studies suggested that micropattern SF films can promote remodeling of the injured tendon. In addition, immunohistochemistry (IHC) results showed that tendon marker genes were significantly increased in the micropattern SF film repair group. Transcriptomic and proteomic analyses demonstrated that micropattern SF film-induced genes and proteins in TSPCs were mainly enriched in the focal adhesion kinase (FAK)/actin and phosphoinositide 3-kinase (PI3K)/AKT pathways. Western blot analysis showed that the expression of integrins 21, tenascin-C (TNC), and tenomodulin (TNMD) and the phosphorylation of AKT were significantly increased in the micropattern SF film group, which could be abrogated by applying PI3K/AKT inhibitors.

Conclusion: Micropattern SF films modified by water annealing can promote remodeling of the injured tendon and regulate the tendon differentiation of TSPCs through the 21/FAK/PI3K/AKT signaling pathway . Therefore, they have great medical value in tendon repair.