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Current wound-healing strategies still fall short in achieving scarless regeneration. Adult wounds often heal in the form of scars, leading to functional impairment and aesthetic concerns. In contrast, fetal wounds exhibit a remarkable capacity for scarless regeneration due to their unique immune environment and regenerative cellular responses. This review systematically elucidates the key mechanisms underlying scarring and contrasts them with the hallmarks of fetal scarless healing. We then comprehensively explore engineering strategies to minimize scar formation in adults, with a focus on the combined application of regenerative biomaterials, bioactive factors, and cell therapies. Particularly emphasis is placed on novel intelligent biomaterials for reprogramming wound immune microenvironment and precise delivery strategies of "spatiotemporal sequential" or "on-demand". These innovations signify a shift toward precise and controlled therapeutic intervention, offering new pathways for skin regeneration that enhances both functionality and aesthetics.
Weng et al. (Fri,) studied this question.