{"title":"基于脱细胞的生物活性异种移植物改良策略促进肌腱修复。","authors":"Haocheng Jin, Yuhao Kang, Haihan Gao, Zhiqi Lin, Dongcheng Huang, Zhi Zheng, Jinzhong Zhao, Liren Wang, Jia Jiang","doi":"10.1002/adhm.202302660","DOIUrl":null,"url":null,"abstract":"<p>Xenografts have emerged as a promising option for severe tendon defects treatment. However, despite undergoing decellularization, concerns still remain regarding the immunogenicity of xenografts. Because certain components within the extracellular matrix also possess immunogenicity. In this study, a novel strategy of post-decellularization modification aimed at preserving the endogenous capacity of cells on collagen synthesis to mask antigenic epitopes in extracellular matrix is proposed. To implement this strategy, a human-derived rosiglitazone-loaded decellularized extracellular matrix (R-dECM) is developed. R-dECM can release rosiglitazone for over 7 days in vitro. By suppressing M1 macrophage polarization, R-dECM protects the migration and collagen synthesis abilities of tendon-derived stem cells (TDSCs), while also stabilizing the phenotype of M2 macrophages in vitro. RNA sequencing reveals R-dECM can mitigate the detrimental crosstalk between TDSCs and inflammatory cells. When applied to a rat patellar tendon defect model, R-dECM effectively inhibits early inflammation, preventing chronic inflammation. Its duration of function far exceeds the release time of rosiglitazone, implying the establishment of immune evasion, confirming the effectiveness of the proposed strategy. And R-dECM demonstrates superior tendon repair outcomes compared to dECM. Thus, this study provides a novel bioactive scaffold with the potential to enhance the long-term clinical outcomes of xenogeneic tendon grafts.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":null,"pages":null},"PeriodicalIF":10.0000,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Decellularization-Based Modification Strategy for Bioactive Xenografts Promoting Tendon Repair\",\"authors\":\"Haocheng Jin, Yuhao Kang, Haihan Gao, Zhiqi Lin, Dongcheng Huang, Zhi Zheng, Jinzhong Zhao, Liren Wang, Jia Jiang\",\"doi\":\"10.1002/adhm.202302660\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Xenografts have emerged as a promising option for severe tendon defects treatment. However, despite undergoing decellularization, concerns still remain regarding the immunogenicity of xenografts. Because certain components within the extracellular matrix also possess immunogenicity. In this study, a novel strategy of post-decellularization modification aimed at preserving the endogenous capacity of cells on collagen synthesis to mask antigenic epitopes in extracellular matrix is proposed. To implement this strategy, a human-derived rosiglitazone-loaded decellularized extracellular matrix (R-dECM) is developed. R-dECM can release rosiglitazone for over 7 days in vitro. By suppressing M1 macrophage polarization, R-dECM protects the migration and collagen synthesis abilities of tendon-derived stem cells (TDSCs), while also stabilizing the phenotype of M2 macrophages in vitro. RNA sequencing reveals R-dECM can mitigate the detrimental crosstalk between TDSCs and inflammatory cells. When applied to a rat patellar tendon defect model, R-dECM effectively inhibits early inflammation, preventing chronic inflammation. Its duration of function far exceeds the release time of rosiglitazone, implying the establishment of immune evasion, confirming the effectiveness of the proposed strategy. And R-dECM demonstrates superior tendon repair outcomes compared to dECM. Thus, this study provides a novel bioactive scaffold with the potential to enhance the long-term clinical outcomes of xenogeneic tendon grafts.</p>\",\"PeriodicalId\":113,\"journal\":{\"name\":\"Advanced Healthcare Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.0000,\"publicationDate\":\"2023-10-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced Healthcare Materials\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/adhm.202302660\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Healthcare Materials","FirstCategoryId":"5","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/adhm.202302660","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
Decellularization-Based Modification Strategy for Bioactive Xenografts Promoting Tendon Repair
Xenografts have emerged as a promising option for severe tendon defects treatment. However, despite undergoing decellularization, concerns still remain regarding the immunogenicity of xenografts. Because certain components within the extracellular matrix also possess immunogenicity. In this study, a novel strategy of post-decellularization modification aimed at preserving the endogenous capacity of cells on collagen synthesis to mask antigenic epitopes in extracellular matrix is proposed. To implement this strategy, a human-derived rosiglitazone-loaded decellularized extracellular matrix (R-dECM) is developed. R-dECM can release rosiglitazone for over 7 days in vitro. By suppressing M1 macrophage polarization, R-dECM protects the migration and collagen synthesis abilities of tendon-derived stem cells (TDSCs), while also stabilizing the phenotype of M2 macrophages in vitro. RNA sequencing reveals R-dECM can mitigate the detrimental crosstalk between TDSCs and inflammatory cells. When applied to a rat patellar tendon defect model, R-dECM effectively inhibits early inflammation, preventing chronic inflammation. Its duration of function far exceeds the release time of rosiglitazone, implying the establishment of immune evasion, confirming the effectiveness of the proposed strategy. And R-dECM demonstrates superior tendon repair outcomes compared to dECM. Thus, this study provides a novel bioactive scaffold with the potential to enhance the long-term clinical outcomes of xenogeneic tendon grafts.
期刊介绍:
Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.