TY - JOUR
T1 - GelMA hydrogel-loaded extracellular vesicles derived from keratinocytes promote skin microvasculature regeneration and wound healing in diabetic mice through activation of the PDGF-induced PI3K/AKT pathway
AU - Li, Qian
AU - Zhou, Leilei
AU - Li, Wenqiang
AU - Zhao, Weiheng
AU - Chen, Weimin
AU - AlQranei, Mohammed S.
AU - Bi, Jiarui
AU - Huang, Ping
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Objective: This study explores how extracellular vesicles (EVs) derived from keratinocytes cultured in Gelatin Methacryloyl (GelMA) hydrogels facilitate microvascular regeneration and enhance wound repair in diabetic skin ulcers. Methods: EVs were harvested from keratinocyte cultures via ultracentrifugation and ultrafiltration, followed by characterization. Their uptake and angiogenic effects on human umbilical vein endothelial cells (HUVECs) were assessed in the following experimentations. Transcriptomic profiling of EV-treated HUVECs identified angiogenesis-related gene expression changes. A diabetic murine wound model was established and validated via glycemic profiling and pancreatic histology. In vivo effects of GelMA-EVs were evaluated through wound closure rates, histology (re-epithelialization, vascularization, collagen deposition), CD31 staining, and microvascular imaging. Results: Keratinocyte-derived EVs significantly enhanced HUVEC proliferation, migration, and tube formation. Mechanistic studies reported elevated PDGF expression, activating the PI3K/AKT pathway. In vivo experiments validated that GelMA hydrogel-loaded EVs increased PDGF expression in wound tissues, promoting microvascular reconstruction and accelerating wound healing in diabetic mouse skin ulcers. Conclusion: GelMA hydrogel-loaded EVs derived from keratinocytes upregulate PDGF, activating the PI3K/AKT pathway to promote microvascular network reconstruction and enhance wound healing in diabetic mouse skin ulcers.
AB - Objective: This study explores how extracellular vesicles (EVs) derived from keratinocytes cultured in Gelatin Methacryloyl (GelMA) hydrogels facilitate microvascular regeneration and enhance wound repair in diabetic skin ulcers. Methods: EVs were harvested from keratinocyte cultures via ultracentrifugation and ultrafiltration, followed by characterization. Their uptake and angiogenic effects on human umbilical vein endothelial cells (HUVECs) were assessed in the following experimentations. Transcriptomic profiling of EV-treated HUVECs identified angiogenesis-related gene expression changes. A diabetic murine wound model was established and validated via glycemic profiling and pancreatic histology. In vivo effects of GelMA-EVs were evaluated through wound closure rates, histology (re-epithelialization, vascularization, collagen deposition), CD31 staining, and microvascular imaging. Results: Keratinocyte-derived EVs significantly enhanced HUVEC proliferation, migration, and tube formation. Mechanistic studies reported elevated PDGF expression, activating the PI3K/AKT pathway. In vivo experiments validated that GelMA hydrogel-loaded EVs increased PDGF expression in wound tissues, promoting microvascular reconstruction and accelerating wound healing in diabetic mouse skin ulcers. Conclusion: GelMA hydrogel-loaded EVs derived from keratinocytes upregulate PDGF, activating the PI3K/AKT pathway to promote microvascular network reconstruction and enhance wound healing in diabetic mouse skin ulcers.
KW - Diabetic skin ulcer
KW - Extracellular vesicles
KW - Gelatin methacryloyl hydrogel
KW - PDGF
KW - PI3K/AKT pathway
UR - https://www.scopus.com/pages/publications/105007974501
U2 - 10.1007/s10565-025-10062-2
DO - 10.1007/s10565-025-10062-2
M3 - Article
C2 - 40515797
AN - SCOPUS:105007974501
SN - 0742-2091
VL - 41
JO - Cell Biology and Toxicology
JF - Cell Biology and Toxicology
IS - 1
M1 - 103
ER -