Selenomethionine in gelatin methacryloyl hydrogels:Modulating ferroptosis to attenuate skin aging

During skin aging,the degeneration of epidermal stem cells(EpiSCs)leads to diminished wound healing capabilities and epidermal disintegration.This study tackles this issue through a comprehensive analysis combining transcriptomics and untargeted metabolomics,revealing age-dependent alterations in the Gpx gene family and arachidonic acid(AA)metabolic networks,resulting in enhanced ferroptosis.Selenomethionine(Se-Met)could enhance GPX4 expression,thereby assisting EpiSCs in countering AA-induced mitochondrial damage and ferroptosis.Additionally,Se-Met demonstrates antioxidative characteristics and extensive ultraviolet absorption.For the sustained and controllable release of Se-Met,it was covalently grafted to UV-responsive GelMA hydrogels via AC-PEG-NHS tethers.The Se-Met@GelMA hydrogel effectively accelerated wound healing in a chronological aging mice model,by inhibiting lipid peroxidation and ferroptosis with augmented GPX4 expression.Moreover,in a photoaging model,this hydrogel significantly mitigated inflammatory responses,extracellular matrix remodeling,and ferroptosis in UV-exposed mice.These characteristics render Se-Met@GelMA hydrogel valuable in practical clinical applications.