Background:Diabetic wounds feature a high-glucose and acidic microenvironment that impairs macrophage polarization and healing.Adiposederived stem cell-derived exosomes(ADSC-exos)show therapeutic potential but suffer ...Background:Diabetic wounds feature a high-glucose and acidic microenvironment that impairs macrophage polarization and healing.Adiposederived 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.Methods:A 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.Results:The 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.Conclusion:The smart hydrogel facilitates diabetic wound healing through microenvironment-responsive ADSC-exos release and Notch/NFκB/NLRP3 pathway inhibition,offering a promising strategy for chronic wound treatment.展开更多
基金supported by the Natural Science Foundation of Shaanxi Province(No.2024JC-YBQN-0407)National Natural Science Foundation of China(No.81530064)+3 种基金China Postdoctoral Science Foundation(No.2023 M732753)National Natural Science Foundation of China(No.81772071)National Natural Science Foundation of China(No.82172210)Open Fund of Key Laboratory for Intelligent Nano Materials and Devices of the Ministry of Education NJ2023002(INMD-2023 M01).
文摘Background:Diabetic wounds feature a high-glucose and acidic microenvironment that impairs macrophage polarization and healing.Adiposederived 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.Methods:A 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.Results:The 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.Conclusion:The smart hydrogel facilitates diabetic wound healing through microenvironment-responsive ADSC-exos release and Notch/NFκB/NLRP3 pathway inhibition,offering a promising strategy for chronic wound treatment.
