Objective:This study aims to explore the therapeutic potential of decellularized adipose matrix(DAM)in rejuvenating photoaged skin by modulating the immune microenvironment.Impact Statement:DAM effectively induces M1 ...Objective:This study aims to explore the therapeutic potential of decellularized adipose matrix(DAM)in rejuvenating photoaged skin by modulating the immune microenvironment.Impact Statement:DAM effectively induces M1 to M2 macrophage polarization and rescues the function of photoaged fibroblasts through paracrine mechanisms,providing a novel strategy for skin antiaging through immune microenvironment remodeling.Introduction:Photoaging,triggered by prolonged ultraviolet exposure,is marked by the depletion of skin structural elements and a persistent inflammatory environment.Current clinical interventions primarily target structural defects,while immune modulation remains underexplored.Therefore,developing biomaterials with both extracellular matrix(ECM)replenishment and immune regulatory functions is crucial for skin regeneration.Methods:A photoaged mouse model was established using ultraviolet B irradiation to validate the inflammatory microenvironment.DAM was prepared via physicochemical decellularization and assessed in vitro for its effects on macrophage polarization and macrophage-fibroblast cross-talk.A DAM-functionalized hyaluronic acid(HA/DAM)hydrogel was developed and evaluated for its effects on skin rejuvenation via subcutaneous injection.Results:In vitro experiments demonstrated that DAM substantially promoted M2 macrophage polarization,and M2-macrophage-conditioned medium further improved fibroblast functions,including oxidative stress resistance,migration,and ECM synthesis.In vivo,HA/DAM hydrogel not only increased dermal thickness and collagen density but also restructured the immune microenvironment through M2 macrophage polarization.Conclusion:DAM offers a novel therapeutic approach for skin rejuvenation by modulating the immune microenvironment,demonstrating notable clinical potential.展开更多
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(grant no.2024ZD0530900)the International Cooperation Project of the National Natural Science Foundation of China(grant no.W2412121).
文摘Objective:This study aims to explore the therapeutic potential of decellularized adipose matrix(DAM)in rejuvenating photoaged skin by modulating the immune microenvironment.Impact Statement:DAM effectively induces M1 to M2 macrophage polarization and rescues the function of photoaged fibroblasts through paracrine mechanisms,providing a novel strategy for skin antiaging through immune microenvironment remodeling.Introduction:Photoaging,triggered by prolonged ultraviolet exposure,is marked by the depletion of skin structural elements and a persistent inflammatory environment.Current clinical interventions primarily target structural defects,while immune modulation remains underexplored.Therefore,developing biomaterials with both extracellular matrix(ECM)replenishment and immune regulatory functions is crucial for skin regeneration.Methods:A photoaged mouse model was established using ultraviolet B irradiation to validate the inflammatory microenvironment.DAM was prepared via physicochemical decellularization and assessed in vitro for its effects on macrophage polarization and macrophage-fibroblast cross-talk.A DAM-functionalized hyaluronic acid(HA/DAM)hydrogel was developed and evaluated for its effects on skin rejuvenation via subcutaneous injection.Results:In vitro experiments demonstrated that DAM substantially promoted M2 macrophage polarization,and M2-macrophage-conditioned medium further improved fibroblast functions,including oxidative stress resistance,migration,and ECM synthesis.In vivo,HA/DAM hydrogel not only increased dermal thickness and collagen density but also restructured the immune microenvironment through M2 macrophage polarization.Conclusion:DAM offers a novel therapeutic approach for skin rejuvenation by modulating the immune microenvironment,demonstrating notable clinical potential.
