Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the α 2 β 1/FAK/PI3K/AKT Signaling Pathway In Vitro

Kang Lu; Hong Tang; Yang Wang; Liyuan Wang; Mei Zhou; Gang He; Hao Lu; Chuyue Tang; Wan Chen; Xiaoqing Ma; Kanglai Tang; Zhongliang Deng

doi:10.1155/2023/2915826

Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the α 2 β 1/FAK/PI3K/AKT Signaling Pathway In Vitro

Stem Cells Int. 2023 Jan 13:2023:2915826. doi: 10.1155/2023/2915826. eCollection 2023.

Authors

Kang Lu¹, Hong Tang², Yang Wang¹, Liyuan Wang¹, Mei Zhou², Gang He², Hao Lu³, Chuyue Tang², Wan Chen², Xiaoqing Ma⁴, Kanglai Tang², Zhongliang Deng¹

Affiliations

¹ Department of Orthopedics-Spine Surgery Center, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
² Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
³ State Key Laboratory of New Materials Composite Technology, Wuhan University of Technology, Wuhan, Hubei, China.
⁴ School of Chemistry and Chemical Engineering, Yangtze Normal University, Chongqing, China.

Abstract

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 in vivo. Then, we seeded TSPCs on SF films in vitro 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 in vivo 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 α2β1, 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 in vivo and regulate the tendon differentiation of TSPCs through the α2β1/FAK/PI3K/AKT signaling pathway in vitro. Therefore, they have great medical value in tendon repair.