Treatment of Denervated Muscle Atrophy by Injectable Dual‐Responsive Hydrogels Loaded with Extracellular Vesicles
Abstract Denervated muscle atrophy, a common outcome of nerve injury, often results in irreversible fibrosis due to the limited effectiveness of current therapeutic interventions. While extracellular vesicles (EVs) offer promise for treating muscle atrophy, their therapeutic potential is hindered by...
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| Format: | Article |
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202412248 |
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| author | Ziheng Bu Jianxing Jing Wei Liu Zhen Fan Junchao Huang Zheng Zhou Jianhai Hu Jinxi An Jiachang Hong Jianing Yu Daolin Tang Min Sun Jianzhong Du Peng Wu |
| author_facet | Ziheng Bu Jianxing Jing Wei Liu Zhen Fan Junchao Huang Zheng Zhou Jianhai Hu Jinxi An Jiachang Hong Jianing Yu Daolin Tang Min Sun Jianzhong Du Peng Wu |
| author_sort | Ziheng Bu |
| collection | DOAJ |
| description | Abstract Denervated muscle atrophy, a common outcome of nerve injury, often results in irreversible fibrosis due to the limited effectiveness of current therapeutic interventions. While extracellular vesicles (EVs) offer promise for treating muscle atrophy, their therapeutic potential is hindered by challenges in delivery and bioactivity within the complex microenvironment of the injury site. To address this issue, an injectable hydrogel is developed that is responsive to both ultrasound and pH, with inherent anti‐inflammatory and antioxidant properties, designed to improve the targeted delivery of stem cell‐derived EVs. This hydrogel system allows for controlled release of EVs from human umbilical cord mesenchymal stem cells (HUC‐MSCs), adapting to the specific conditions of the injury environment. In vivo studies using a rat model of nerve injury demonstrated that the EV‐loaded hydrogel (EVs@UR‐gel) significantly preserved muscle function. Six weeks post‐nerve reconstruction, treated rats exhibited muscle strength, circumference, and wet weight reaching 89.53 ± 0.96%, 76.02 ± 7.49%, and 88.0 ± 2.65% of healthy controls, respectively, alongside an improvement in the sciatic nerve index (−0.11 ± 0.09). This platform presents a novel therapeutic approach by maintaining EV bioactivity, enabling tunable release based on the disease state, and facilitating the restoration of muscle structure and function. |
| format | Article |
| id | doaj-art-cb3d71e6c0074b4eb0d234ca109b154a |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-cb3d71e6c0074b4eb0d234ca109b154a2025-08-20T03:10:53ZengWileyAdvanced Science2198-38442025-03-011210n/an/a10.1002/advs.202412248Treatment of Denervated Muscle Atrophy by Injectable Dual‐Responsive Hydrogels Loaded with Extracellular VesiclesZiheng Bu0Jianxing Jing1Wei Liu2Zhen Fan3Junchao Huang4Zheng Zhou5Jianhai Hu6Jinxi An7Jiachang Hong8Jianing Yu9Daolin Tang10Min Sun11Jianzhong Du12Peng Wu13Department of Orthopedics Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai 200072 ChinaDepartment of Polymeric Materials School of Materials Science and Engineering Tongji University 4800 Caoan Road Shanghai 201804 ChinaDepartment of Orthopedics Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai 200072 ChinaDepartment of Polymeric Materials School of Materials Science and Engineering Tongji University 4800 Caoan Road Shanghai 201804 ChinaDepartment of Orthopedics Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai 200072 ChinaDepartment of Orthopedics Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai 200072 ChinaDepartment of Orthopedics Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai 200072 ChinaSchool of Medicine Anhui University of Science & Technology 168 Taifeng Street, Shannan New District Huainan Anhui 232000 ChinaDepartment of Orthopedics Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai 200072 ChinaSchool of Medicine Anhui University of Science & Technology 168 Taifeng Street, Shannan New District Huainan Anhui 232000 ChinaDepartment of Surgery UT Southwestern Medical Center Dallas Texas 75390 USADepartment of Orthopedics Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai 200072 ChinaDepartment of Orthopedics Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai 200072 ChinaDepartment of Orthopedics Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai 200072 ChinaAbstract Denervated muscle atrophy, a common outcome of nerve injury, often results in irreversible fibrosis due to the limited effectiveness of current therapeutic interventions. While extracellular vesicles (EVs) offer promise for treating muscle atrophy, their therapeutic potential is hindered by challenges in delivery and bioactivity within the complex microenvironment of the injury site. To address this issue, an injectable hydrogel is developed that is responsive to both ultrasound and pH, with inherent anti‐inflammatory and antioxidant properties, designed to improve the targeted delivery of stem cell‐derived EVs. This hydrogel system allows for controlled release of EVs from human umbilical cord mesenchymal stem cells (HUC‐MSCs), adapting to the specific conditions of the injury environment. In vivo studies using a rat model of nerve injury demonstrated that the EV‐loaded hydrogel (EVs@UR‐gel) significantly preserved muscle function. Six weeks post‐nerve reconstruction, treated rats exhibited muscle strength, circumference, and wet weight reaching 89.53 ± 0.96%, 76.02 ± 7.49%, and 88.0 ± 2.65% of healthy controls, respectively, alongside an improvement in the sciatic nerve index (−0.11 ± 0.09). This platform presents a novel therapeutic approach by maintaining EV bioactivity, enabling tunable release based on the disease state, and facilitating the restoration of muscle structure and function.https://doi.org/10.1002/advs.202412248denervated muscle atrophyextracellular vesicleshydrogelultrasound responsiveness |
| spellingShingle | Ziheng Bu Jianxing Jing Wei Liu Zhen Fan Junchao Huang Zheng Zhou Jianhai Hu Jinxi An Jiachang Hong Jianing Yu Daolin Tang Min Sun Jianzhong Du Peng Wu Treatment of Denervated Muscle Atrophy by Injectable Dual‐Responsive Hydrogels Loaded with Extracellular Vesicles Advanced Science denervated muscle atrophy extracellular vesicles hydrogel ultrasound responsiveness |
| title | Treatment of Denervated Muscle Atrophy by Injectable Dual‐Responsive Hydrogels Loaded with Extracellular Vesicles |
| title_full | Treatment of Denervated Muscle Atrophy by Injectable Dual‐Responsive Hydrogels Loaded with Extracellular Vesicles |
| title_fullStr | Treatment of Denervated Muscle Atrophy by Injectable Dual‐Responsive Hydrogels Loaded with Extracellular Vesicles |
| title_full_unstemmed | Treatment of Denervated Muscle Atrophy by Injectable Dual‐Responsive Hydrogels Loaded with Extracellular Vesicles |
| title_short | Treatment of Denervated Muscle Atrophy by Injectable Dual‐Responsive Hydrogels Loaded with Extracellular Vesicles |
| title_sort | treatment of denervated muscle atrophy by injectable dual responsive hydrogels loaded with extracellular vesicles |
| topic | denervated muscle atrophy extracellular vesicles hydrogel ultrasound responsiveness |
| url | https://doi.org/10.1002/advs.202412248 |
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