Slow wound healing in the elderly has attracted much attention recently due to the associated infection risks and decreased longevity.The“brain-skin axis”theory suggests that abnormalities in the brain and nervous s...Slow wound healing in the elderly has attracted much attention recently due to the associated infection risks and decreased longevity.The“brain-skin axis”theory suggests that abnormalities in the brain and nervous system can lead to skin degeneration because abnormal mental states,like chronic stress,can have negative physiological and functional effects on the skin through a variety of processes,resulting in delayed wound healing and accelerated skin aging.However,it remains unclear whether maintaining a youthful brain has beneficial effects on aged skin healing.In light of this,we identified youthful brain-derived extracellular vesicles(YBEVs)and created a composite GelMA hydrogel material that encourages scarless wound healing in aged skin.We found that YBEVs reduce the expression of senescence,senescence-associated secretory phenotypes,and inflammation-associated proteins,and even restore dysfunction in senescent cells.Furthermore,by encouraging collagen deposition,angiogenesis,epidermal and dermal regeneration,and folliculogenesis,we demonstrated that YBEV-containing composite hydrogels accelerated scarless wound healing in skin wounds of aged rats.The pro-repairing speed and effect of this composite hydrogel even matched that of young rats.Subsequent proteomic analysis revealed the presence of numerous proteins within YBEVs,some of which may play a role in the regulation of skin energy intake,particularly through oxidative phosphorylation and mitochondrial function.In conclusion,the findings suggest that maintaining a youthful brain could potentially alleviate skin aging,and the proposed YBEVs-GelMA hydrogel emerges as a promising strategy for addressing age-related impairments in skin healing.展开更多
基金supported by the National Natural Science Foundation of China(grant numbers 82470974 and 82471602)the Zhejiang Provincial Natural Science Foundation of China(grant number LY24H140001)the Funds of the Central Government Guiding Local Science and Technology Development(grant number 2023ZY1060).
文摘Slow wound healing in the elderly has attracted much attention recently due to the associated infection risks and decreased longevity.The“brain-skin axis”theory suggests that abnormalities in the brain and nervous system can lead to skin degeneration because abnormal mental states,like chronic stress,can have negative physiological and functional effects on the skin through a variety of processes,resulting in delayed wound healing and accelerated skin aging.However,it remains unclear whether maintaining a youthful brain has beneficial effects on aged skin healing.In light of this,we identified youthful brain-derived extracellular vesicles(YBEVs)and created a composite GelMA hydrogel material that encourages scarless wound healing in aged skin.We found that YBEVs reduce the expression of senescence,senescence-associated secretory phenotypes,and inflammation-associated proteins,and even restore dysfunction in senescent cells.Furthermore,by encouraging collagen deposition,angiogenesis,epidermal and dermal regeneration,and folliculogenesis,we demonstrated that YBEV-containing composite hydrogels accelerated scarless wound healing in skin wounds of aged rats.The pro-repairing speed and effect of this composite hydrogel even matched that of young rats.Subsequent proteomic analysis revealed the presence of numerous proteins within YBEVs,some of which may play a role in the regulation of skin energy intake,particularly through oxidative phosphorylation and mitochondrial function.In conclusion,the findings suggest that maintaining a youthful brain could potentially alleviate skin aging,and the proposed YBEVs-GelMA hydrogel emerges as a promising strategy for addressing age-related impairments in skin healing.
