2. Academic Validation
  3. Mitochondrial biogenesis modulation by silicon-stimulated mesenchymal stem cells-derived extracellular vesicles drives angio- and lymphangiogenesis in chronic wound healing

Mitochondrial biogenesis modulation by silicon-stimulated mesenchymal stem cells-derived extracellular vesicles drives angio- and lymphangiogenesis in chronic wound healing

  • Mater Today Bio. 2025 Dec 3:35:102629. doi: 10.1016/j.mtbio.2025.102629.
Min-Hua Yu 1 2,  Yen-Hong Lin 3,  En-Wei Liu 4,  Tai-Yi Hsu-Jiang 2,  Der-Yang Cho 2 5 6 7 8,  Jian-Jr Lee 2 4 9 10,  Ming-You Shie 2 3 5 11
Affiliations

Affiliations

  • 1 Institute of Translational Medicine and New Drug Development, China Medical University, Taichung, 406040, Taiwan.
  • 2 Xenotransplantation Translational Research Center, China Medical University Hospital, Taichung, 404327, Taiwan.
  • 3 Department of Biomedical Engineering, China Medical University, Taichung, 406040, Taiwan.
  • 4 Department of Plastic and Reconstructive Surgery, China Medical University Hospital, Taichung, 404327, Taiwan.
  • 5 Research & Development Center for x-Dimensional Extracellular Vesicles, China Medical University Hospital, Taichung, 404327, Taiwan.
  • 6 Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 406040, Taiwan.
  • 7 Department of Neurosurgery, China Medical University Hospital, Taichung, 404327, Taiwan.
  • 8 Translational Cell Therapy Center, Department of Medical Research, China Medical University Hospital, Taichung, 404327, Taiwan.
  • 9 School of Medicine, China Medical University, Taichung, 406040, Taiwan.
  • 10 Department of Plastic and Reconstructive Surgery, Taichung Municipal Geriatric Rehabilitation General Hospital, Taichung, 406004, Taiwan.
  • 11 Department of Bioinformatics and Medical Engineering, Asia University, Taichung, 413305, Taiwan.
PMID: 41450334 DOI: 10.1016/j.mtbio.2025.102629
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; however, their efficacy and immunomodulation can be enhanced through bioactivation. In this study, we incorporated calcium silicate-stimulated ADSC-derived EVs (CSEVs) into Collagen hydrogels to create a sustained-release system to promote diabetic wound healing. CSEVs exhibit enhanced protein content, surface marker expression, and bioactive cargo enriched with proangiogenic and anti-inflammatory factors. In addition, the suppression of proinflammatory signaling, polarization of M2 macrophages, stimulation of angiogenesis and lymphangiogenesis, and activation of mitochondrial function in dermal fibroblasts were among the many effects of CSEVs on the wound microenvironment. Moreover, miR-31 in CSEVs demonstrated an important factor in promoting difficult wound repair. These results highlight the potential of Collagen scaffolds incorporated with CSEVs as strong acellular substrates for improving wound healing in diabetic environments. CSEVs and miRNA-mediated cues work together to overcome regeneration constraints of chronic wounds.

Keywords

Calcium silicate; Diabetic wound healing; Extracellular vesicles; Immunomodulation; miR-31.

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