PMID- 36684388 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230201 IS - 1687-966X (Print) IS - 1687-9678 (Electronic) VI - 2023 DP - 2023 TI - Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the alpha2beta1/FAK/PI3K/AKT Signaling Pathway In Vitro. PG - 2915826 LID - 10.1155/2023/2915826 [doi] LID - 2915826 AB - 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 alpha2beta1, 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 alpha2beta1/FAK/PI3K/AKT signaling pathway in vitro. Therefore, they have great medical value in tendon repair. CI - Copyright (c) 2023 Kang Lu et al. FAU - Lu, Kang AU - Lu K AD - Department of Orthopedics-Spine Surgery Center, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. FAU - Tang, Hong AU - Tang H AUID- ORCID: 0000-0003-0011-6575 AD - 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. FAU - Wang, Yang AU - Wang Y AD - Department of Orthopedics-Spine Surgery Center, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. FAU - Wang, Liyuan AU - Wang L AD - Department of Orthopedics-Spine Surgery Center, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. FAU - Zhou, Mei AU - Zhou M AUID- ORCID: 0000-0002-6481-2206 AD - 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. FAU - He, Gang AU - He G AUID- ORCID: 0000-0001-9806-4069 AD - 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. FAU - Lu, Hao AU - Lu H AD - State Key Laboratory of New Materials Composite Technology, Wuhan University of Technology, Wuhan, Hubei, China. FAU - Tang, Chuyue AU - Tang C AD - 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. FAU - Chen, Wan AU - Chen W AD - 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. FAU - Ma, Xiaoqing AU - Ma X AUID- ORCID: 0000-0001-6949-529X AD - School of Chemistry and Chemical Engineering, Yangtze Normal University, Chongqing, China. FAU - Tang, Kanglai AU - Tang K AUID- ORCID: 0000-0002-0370-106X AD - 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. FAU - Deng, Zhongliang AU - Deng Z AUID- ORCID: 0000-0001-5330-3062 AD - Department of Orthopedics-Spine Surgery Center, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. LA - eng PT - Journal Article DEP - 20230113 PL - United States TA - Stem Cells Int JT - Stem cells international JID - 101535822 PMC - PMC9859702 COIS- The authors declare no conflicts of interest. EDAT- 2023/01/24 06:00 MHDA- 2023/01/24 06:01 PMCR- 2023/01/13 CRDT- 2023/01/23 04:22 PHST- 2022/06/23 00:00 [received] PHST- 2022/11/23 00:00 [revised] PHST- 2022/12/08 00:00 [accepted] PHST- 2023/01/23 04:22 [entrez] PHST- 2023/01/24 06:00 [pubmed] PHST- 2023/01/24 06:01 [medline] PHST- 2023/01/13 00:00 [pmc-release] AID - 10.1155/2023/2915826 [doi] PST - epublish SO - Stem Cells Int. 2023 Jan 13;2023:2915826. doi: 10.1155/2023/2915826. eCollection 2023.