Immunomodulation effects of collagen hydrogel encapsulating extracellular vesicles derived from calcium silicate stimulated-adipose mesenchymal stem cells for diabetic healing

• Published in: Journal of nanobiotechnology Vol. 23; no. 1; pp. 45 - 21
• Main Authors: Lin, Yen-Hong, Chen, Yeh, Liu, En-Wei, Chen, Mei-Chih, Yu, Min-Hua, Chen, Cheng-Yu, Ho, Chia-Che, Hsu-Jiang, Tai-Yi, Lee, Jian-Jr, Cho, Der-Yang, Shie, Ming-You
• Format: Journal Article
• Language: English
• Published: London BioMed Central 27.01.2025; BioMed Central Ltd; BMC
• Subjects: Adipose Tissue - cytology; Animals; Biotechnology; Calcium Compounds - chemistry; Calcium Compounds - pharmacology; Calcium silicate; Care and treatment; Cell Movement - drug effects; Cell Proliferation - drug effects; Chemistry; Chemistry and Materials Science; Collagen; Collagen - chemistry; Collagen - pharmacology; Composition; Cytokines - metabolism; Diabetes Mellitus, Experimental; Diabetic wound healing; Extracellular vesicles; Extracellular Vesicles - chemistry; Extracellular Vesicles - metabolism; Gels (Pharmacy); Health aspects; Humans; Hydrogels - chemistry; Hydrogels - pharmacology; Immunomodulation; Immunomodulation - drug effects; Inflammation; Male; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Molecular Medicine; Nanotechnology; Rabbits; Silicates - chemistry; Silicates - pharmacology; Wound Healing - drug effects; Wounds and injuries; United States; Extracellular vesicles; Immunomodulation; Diabetic wound healing; Calcium silicate
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-025-03097-4

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