Immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated-adipose mesenchymal stem cells for diabetic healing
Abstract Diabetic wounds are characterized by chronic inflammation, reduced angiogenesis, and insufficient collagen deposition, leading to impaired healing. Extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSC) offer a promising cell-free therapeutic strategy, yet t...
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03097-4 |
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| author | Yen-Hong Lin Yeh Chen En-Wei Liu Mei-Chih Chen Min-Hua Yu Cheng-Yu Chen Chia-Che Ho Tai-Yi Hsu-Jiang Jian-Jr Lee Der-Yang Cho Ming-You Shie |
| author_facet | Yen-Hong Lin Yeh Chen En-Wei Liu Mei-Chih Chen Min-Hua Yu Cheng-Yu Chen Chia-Che Ho Tai-Yi Hsu-Jiang Jian-Jr Lee Der-Yang Cho Ming-You Shie |
| author_sort | Yen-Hong Lin |
| collection | DOAJ |
| description | Abstract Diabetic wounds are characterized by chronic inflammation, reduced angiogenesis, and insufficient collagen deposition, leading to impaired healing. Extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSC) offer a promising cell-free therapeutic strategy, yet their efficacy and immunomodulation can be enhanced through bioactivation. In this study, we developed calcium silicate (CS)-stimulated ADSC-derived EVs (CSEV) incorporated into collagen hydrogels to create a sustained-release system for promoting diabetic wound healing. CSEV exhibited enhanced protein content, surface marker expression, and bioactive cargo enriched with pro-angiogenic and anti-inflammatory factors. In vitro, CSEV-loaded collagen significantly reduced reactive oxygen species production, promoted cell proliferation and migration compared to standard EV-loaded collagen. Cytokine profiling revealed the upregulation of anti-inflammatory cytokines and extracellular matrix components, highlighting their immunomodulatory and regenerative potential. In vivo, histological evaluation of diabetic rabbit models treated with CSEV-loaded collagen revealed superior reepithelialization and organized collagen deposition, indicating accelerated wound closure. These findings underscore the potential of CSEV-loaded collagen hydrogels as an innovative and effective therapeutic platform for enhancing diabetic wound healing by simultaneously addressing inflammation and tissue regeneration. Graphical abstract |
| format | Article |
| id | doaj-art-30fb6fd35fc24a1fba8160f8aab1c853 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-30fb6fd35fc24a1fba8160f8aab1c8532025-02-02T12:41:09ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112110.1186/s12951-025-03097-4Immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated-adipose mesenchymal stem cells for diabetic healingYen-Hong Lin0Yeh Chen1En-Wei Liu2Mei-Chih Chen3Min-Hua Yu4Cheng-Yu Chen5Chia-Che Ho6Tai-Yi Hsu-Jiang7Jian-Jr Lee8Der-Yang Cho9Ming-You Shie10Department of Biomedical Engineering, China Medical UniversityDepartment of Food Science and Biotechnology, National Chung Hsing UniversityDepartment of Plastic and Reconstructive Surgery, China Medical University HospitalTranslational Cell Therapy Center, Department of Medical Research, China Medical University HospitalInstitute of Translational Medicine and New Drug Development, China Medical UniversityResearch & Development Center for x-Dimensional Extracellular Vesicles, Department of Medical Research, China Medical University HospitalDepartment of Bioinformatics and Medical Engineering, Asia UniversitySchool of Medicine, China Medical UniversityDepartment of Plastic and Reconstructive Surgery, China Medical University HospitalResearch & Development Center for x-Dimensional Extracellular Vesicles, Department of Medical Research, China Medical University HospitalDepartment of Biomedical Engineering, China Medical UniversityAbstract Diabetic wounds are characterized by chronic inflammation, reduced angiogenesis, and insufficient collagen deposition, leading to impaired healing. Extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSC) offer a promising cell-free therapeutic strategy, yet their efficacy and immunomodulation can be enhanced through bioactivation. In this study, we developed calcium silicate (CS)-stimulated ADSC-derived EVs (CSEV) incorporated into collagen hydrogels to create a sustained-release system for promoting diabetic wound healing. CSEV exhibited enhanced protein content, surface marker expression, and bioactive cargo enriched with pro-angiogenic and anti-inflammatory factors. In vitro, CSEV-loaded collagen significantly reduced reactive oxygen species production, promoted cell proliferation and migration compared to standard EV-loaded collagen. Cytokine profiling revealed the upregulation of anti-inflammatory cytokines and extracellular matrix components, highlighting their immunomodulatory and regenerative potential. In vivo, histological evaluation of diabetic rabbit models treated with CSEV-loaded collagen revealed superior reepithelialization and organized collagen deposition, indicating accelerated wound closure. These findings underscore the potential of CSEV-loaded collagen hydrogels as an innovative and effective therapeutic platform for enhancing diabetic wound healing by simultaneously addressing inflammation and tissue regeneration. Graphical abstracthttps://doi.org/10.1186/s12951-025-03097-4Extracellular vesiclesCalcium silicateImmunomodulationDiabetic wound healing |
| spellingShingle | Yen-Hong Lin Yeh Chen En-Wei Liu Mei-Chih Chen Min-Hua Yu Cheng-Yu Chen Chia-Che Ho Tai-Yi Hsu-Jiang Jian-Jr Lee Der-Yang Cho Ming-You Shie Immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated-adipose mesenchymal stem cells for diabetic healing Journal of Nanobiotechnology Extracellular vesicles Calcium silicate Immunomodulation Diabetic wound healing |
| title | Immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated-adipose mesenchymal stem cells for diabetic healing |
| title_full | Immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated-adipose mesenchymal stem cells for diabetic healing |
| title_fullStr | Immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated-adipose mesenchymal stem cells for diabetic healing |
| title_full_unstemmed | Immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated-adipose mesenchymal stem cells for diabetic healing |
| title_short | Immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated-adipose mesenchymal stem cells for diabetic healing |
| title_sort | immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated adipose mesenchymal stem cells for diabetic healing |
| topic | Extracellular vesicles Calcium silicate Immunomodulation Diabetic wound healing |
| url | https://doi.org/10.1186/s12951-025-03097-4 |
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