@article{Zhang2025, 
author = {Yue Zhang and Meng Li and Shijie Song and Fenghui Hei and Shaoyang Ma and Jiao Cao and Baolin Guo and Dahai Hu},
title = {Multiple dynamic crosslinked multifunctional hydrogels with glucose/pH dual-responsive adipose-derived stem cells-exosomes-releasing for diabetic wound healing},
year = {2025},
journal = {Burns & Trauma},
volume = {13},
number = {12},
pages = {tkaf059},
keywords = {Glucose/pH dual responsive hydrogels, ADSC-exos, Macrophage, Chronic diabetic wound, Inflammation},
url = {https://www.sciopen.com/article/10.1093/burnst/tkaf059},
doi = {10.1093/burnst/tkaf059},
abstract = {BackgroundDiabetic wounds feature a high-glucose and acidic microenvironment that impairs macrophage polarization and healing. Adipose-derived stem cell-derived exosomes (ADSC-exos) show therapeutic potential but suffer from rapid clearance. This study aimed to develop a smart hydrogel for glucose/pH-responsive ADSC-exos release.MethodsA dual-responsive hydrogel (HAP/OCS/PEG/Ag-E) was fabricated via dynamic triple cross-linking. Characterization included rheometry, mechanical tests, and microscopy. In vitro macrophage polarization was assessed via flow cytometry and Western blot. A diabetic mouse wound model evaluated healing rates, histology, angiogenesis, and inflammation. Proteomics and pathway inhibition studies explored mechanisms. Statistical analysis used t-tests and ANOVA.ResultsThe hydrogel exhibited excellent self-healing, adhesion, and controlled ADSC-exos release under high-glucose/acidic conditions. It promoted M2 macrophage polarization, reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and accelerated wound healing with enhanced angiogenesis and collagen deposition. Mechanistically, the hydrogel suppressed the Notch/NF-κB/NLRP3 signaling pathway.ConclusionThe smart hydrogel facilitates diabetic wound healing through microenvironment-responsive ADSC-exos release and Notch/NF-κB/NLRP3 pathway inhibition, offering a promising strategy for chronic wound treatment.}
}