Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomes
Tendinopathy is a common musculoskeletal disorder in which a significant number of patients do not attain effective therapeutic outcomes. The extent of the inflammatory response and the dynamics of collagen synthesis metabolism are critical factors that influence the intrinsic self-repair capacity o...
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KeAi Communications Co., Ltd.
2025-05-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25000167 |
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| author | Danmei Li Shuai Li Shukun He Hongpu He Guangxun Yuan Binbin Ma Yijun Zhang Chengjie Yuan Zhiqin Liu Zhenhan Deng Jian Xu |
| author_facet | Danmei Li Shuai Li Shukun He Hongpu He Guangxun Yuan Binbin Ma Yijun Zhang Chengjie Yuan Zhiqin Liu Zhenhan Deng Jian Xu |
| author_sort | Danmei Li |
| collection | DOAJ |
| description | Tendinopathy is a common musculoskeletal disorder in which a significant number of patients do not attain effective therapeutic outcomes. The extent of the inflammatory response and the dynamics of collagen synthesis metabolism are critical factors that influence the intrinsic self-repair capacity of tendons. However, the poor microenvironment within the tendon significantly impedes the self-repair process in tendinopathy. In this study, an injectable tendon-derived decellularized extracellular matrix (tdECM) hydrogel was utilized to treat tendinopathy. This hydrogel provides a more cytocompatible microenvironment while retaining certain bioactive factors of native tendon extracellular matrix (ECM), compared to collagen hydrogel. Notably, it was discovered for the first time that the tdECM hydrogel promotes M2 macrophage polarization, thereby exerting an anti-inflammatory effect in vivo. Furthermore, utilizing tdECM as a carrier for the sustained release of tendon-derived stem cells exosomes (TDSCs-Exos), our findings from both in vitro and in vivo studies indicate that the tdECM hydrogel, in conjunction with exosomes, demonstrated a pronounced synergistic enhancement in modulating inflammation, promoting M2 macrophage polarization, and facilitating tendon regeneration and repair efficacy. These results suggest its potential as a promising therapeutic strategy for tendon disorders. |
| format | Article |
| id | doaj-art-788db4c26d6e44ff8afe2a4e553ed1fb |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-788db4c26d6e44ff8afe2a4e553ed1fb2025-01-23T05:27:23ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-05-0147152169Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomesDanmei Li0Shuai Li1Shukun He2Hongpu He3Guangxun Yuan4Binbin Ma5Yijun Zhang6Chengjie Yuan7Zhiqin Liu8Zhenhan Deng9Jian Xu10Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, ChinaDepartment of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, ChinaDepartment of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, ChinaDepartment of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, ChinaDepartment of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, ChinaDepartment of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, ChinaDepartment of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, ChinaDepartment of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, ChinaDepartment of Orthopaedics, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, 412007, ChinaDepartment of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Geriatrics Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China; Corresponding author. Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Corresponding author. Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.Tendinopathy is a common musculoskeletal disorder in which a significant number of patients do not attain effective therapeutic outcomes. The extent of the inflammatory response and the dynamics of collagen synthesis metabolism are critical factors that influence the intrinsic self-repair capacity of tendons. However, the poor microenvironment within the tendon significantly impedes the self-repair process in tendinopathy. In this study, an injectable tendon-derived decellularized extracellular matrix (tdECM) hydrogel was utilized to treat tendinopathy. This hydrogel provides a more cytocompatible microenvironment while retaining certain bioactive factors of native tendon extracellular matrix (ECM), compared to collagen hydrogel. Notably, it was discovered for the first time that the tdECM hydrogel promotes M2 macrophage polarization, thereby exerting an anti-inflammatory effect in vivo. Furthermore, utilizing tdECM as a carrier for the sustained release of tendon-derived stem cells exosomes (TDSCs-Exos), our findings from both in vitro and in vivo studies indicate that the tdECM hydrogel, in conjunction with exosomes, demonstrated a pronounced synergistic enhancement in modulating inflammation, promoting M2 macrophage polarization, and facilitating tendon regeneration and repair efficacy. These results suggest its potential as a promising therapeutic strategy for tendon disorders.http://www.sciencedirect.com/science/article/pii/S2452199X25000167TendinopathyMacrophageTendon-derived stem cell exosomesTendon-derived extracellular matrixHydrogel |
| spellingShingle | Danmei Li Shuai Li Shukun He Hongpu He Guangxun Yuan Binbin Ma Yijun Zhang Chengjie Yuan Zhiqin Liu Zhenhan Deng Jian Xu Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomes Bioactive Materials Tendinopathy Macrophage Tendon-derived stem cell exosomes Tendon-derived extracellular matrix Hydrogel |
| title | Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomes |
| title_full | Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomes |
| title_fullStr | Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomes |
| title_full_unstemmed | Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomes |
| title_short | Restoring tendon microenvironment in tendinopathy: Macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon-derived stem cells exosomes |
| title_sort | restoring tendon microenvironment in tendinopathy macrophage modulation and tendon regeneration with injectable tendon hydrogel and tendon derived stem cells exosomes |
| topic | Tendinopathy Macrophage Tendon-derived stem cell exosomes Tendon-derived extracellular matrix Hydrogel |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25000167 |
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