Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the alpha 2 beta 1/FAK/PI3K/AKT Signaling Pathway In Vitro
作者全名："Lu, Kang; Tang, Hong; Wang, Yang; Wang, Liyuan; Zhou, Mei; He, Gang; Lu, Hao; Tang, Chuyue; Chen, Wan; Ma, Xiaoqing; Tang, Kanglai; Deng, Zhongliang"
作者地址："[Lu, Kang; Wang, Yang; Wang, Liyuan; Deng, Zhongliang] Chongqing Med Univ, Affiliated Hosp 2, Spine Surg Ctr, Dept Orthoped, Chongqing, Peoples R China; [Tang, Hong; Zhou, Mei; He, Gang; Tang, Chuyue; Chen, Wan; Tang, Kanglai] Third Mil Med Univ, Army Med Univ, Southwest Hosp, Sports Med Ctr,Dept Orthoped,State Key Lab Trauma, Chongqing, Peoples R China; [Lu, Hao] Wuhan Univ Technol, State Key Lab New Mat Composite Technol, Wuhan, Hubei, Peoples R China; [Ma, Xiaoqing] Yangtze Normal Univ, Sch Chem & Chem Engn, Chongqing, Peoples R China"
通信作者："Deng, ZL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Spine Surg Ctr, Dept Orthoped, Chongqing, Peoples R China.; Tang, KL (通讯作者)，Third Mil Med Univ, Army Med Univ, Southwest Hosp, Sports Med Ctr,Dept Orthoped,State Key Lab Trauma, Chongqing, Peoples R China.; Ma, XQ (通讯作者)，Yangtze Normal Univ, Sch Chem & Chem Engn, Chongqing, Peoples R China."
来源：STEM CELLS INTERNATIONAL
ESI学科分类：MOLECULAR BIOLOGY & GENETICS
摘要："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 alpha 2 beta 1, 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 alpha 2 beta 1/FAK/PI3K/AKT signaling pathway in vitro. Therefore, they have great medical value in tendon repair."
基金机构：Chongqing Postdoctoral Science Foundation [CSTB2022NSCQ-BHX0614]; Chongqing Talents Funding [CQYC2021059825]; Chongqing Science & Technology Commission [cstc2021jcyj-msxmX0137]; Sports Injury Repair and Reconstruction Research Innovation Group [cstc2020jcyj-cxttX0004]; Spine Surgery Center of the Second Affiliated Hospital of Chongqing Medical University
基金资助正文："AcknowledgmentsThe research was supported by grants from the Chongqing Postdoctoral Science Foundation (CSTB2022NSCQ-BHX0614), the Chongqing Talents Funding (No. CQYC2021059825), the Chongqing Science & Technology Commission (No. cstc2021jcyj-msxmX0137), and the Sports Injury Repair and Reconstruction Research Innovation Group (No. cstc2020jcyj-cxttX0004). The authors would like to thank the Spine Surgery Center of the Second Affiliated Hospital of Chongqing Medical University for the technical support."