Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the α2β1/FAK/PI3K/AKT Signaling Pathway In Vitro

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 repairin...

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Main Authors: Kang Lu, Hong Tang, Yang Wang, Liyuan Wang, Mei Zhou, Gang He, Hao Lu, Chuyue Tang, Wan Chen, Xiaoqing Ma, Kanglai Tang, Zhongliang Deng
Format: Article
Language:English
Published: Hindawi Limited 2023-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2023/2915826
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author Kang Lu
Hong Tang
Yang Wang
Liyuan Wang
Mei Zhou
Gang He
Hao Lu
Chuyue Tang
Wan Chen
Xiaoqing Ma
Kanglai Tang
Zhongliang Deng
author_facet Kang Lu
Hong Tang
Yang Wang
Liyuan Wang
Mei Zhou
Gang He
Hao Lu
Chuyue Tang
Wan Chen
Xiaoqing Ma
Kanglai Tang
Zhongliang Deng
author_sort Kang Lu
collection DOAJ
description 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.
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spelling doaj.art-e6973932a51349318b4a0e85d4ced9462023-01-23T00:56:17ZengHindawi LimitedStem Cells International1687-96782023-01-01202310.1155/2023/2915826Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the α2β1/FAK/PI3K/AKT Signaling Pathway In VitroKang Lu0Hong Tang1Yang Wang2Liyuan Wang3Mei Zhou4Gang He5Hao Lu6Chuyue Tang7Wan Chen8Xiaoqing Ma9Kanglai Tang10Zhongliang Deng11Department of Orthopedics-Spine Surgery CenterDepartment of Orthopedics/Sports Medicine CenterDepartment of Orthopedics-Spine Surgery CenterDepartment of Orthopedics-Spine Surgery CenterDepartment of Orthopedics/Sports Medicine CenterDepartment of Orthopedics/Sports Medicine CenterState Key Laboratory of New Materials Composite TechnologyDepartment of Orthopedics/Sports Medicine CenterDepartment of Orthopedics/Sports Medicine CenterSchool of Chemistry and Chemical EngineeringDepartment of Orthopedics/Sports Medicine CenterDepartment of Orthopedics-Spine Surgery CenterBackground. 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.http://dx.doi.org/10.1155/2023/2915826
spellingShingle Kang Lu
Hong Tang
Yang Wang
Liyuan Wang
Mei Zhou
Gang He
Hao Lu
Chuyue Tang
Wan Chen
Xiaoqing Ma
Kanglai Tang
Zhongliang Deng
Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the α2β1/FAK/PI3K/AKT Signaling Pathway In Vitro
Stem Cells International
title Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the α2β1/FAK/PI3K/AKT Signaling Pathway In Vitro
title_full Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the α2β1/FAK/PI3K/AKT Signaling Pathway In Vitro
title_fullStr Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the α2β1/FAK/PI3K/AKT Signaling Pathway In Vitro
title_full_unstemmed Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the α2β1/FAK/PI3K/AKT Signaling Pathway In Vitro
title_short Micropattern Silk Fibroin Film Facilitates Tendon Repair In Vivo and Promotes Tenogenic Differentiation of Tendon Stem/Progenitor Cells through the α2β1/FAK/PI3K/AKT Signaling Pathway In Vitro
title_sort micropattern silk fibroin film facilitates tendon repair in vivo and promotes tenogenic differentiation of tendon stem progenitor cells through the α2β1 fak pi3k akt signaling pathway in vitro
url http://dx.doi.org/10.1155/2023/2915826
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