Approaching Scarless Wound Healing: From Passive Anti-Fibrotic to Proactive and Programmable Pro-Regenerative...

Pathological scarring after skin wound healing poses a substantial clinical difficulty, essentially representing a fibrotic outcome of dysregulated tissue repair. This review provides a comprehensive analysis of the physiological processes of wound healing and key factors in scar formation, focusing on the unique mechanisms of scarless regeneration models such as early-stage fetuses and spiny mouse (Acomys cahirinus). These models rely heavily on the immune microenvironment's regulation, the dynamic remodeling of the extracellular matrix (ECM), and precise cell behavior regulation to achieve perfect regeneration. Building upon this foundation, this review delves into emerging scar prevention methods from the perspective of tissue engineering materials. These encompass multi-dimensional interventions, including the construction of biomimetic microenvironments, regulation of key cell fates, sequential multi-target intervention in pathological processes, and the integration of smart materials with advanced manufacturing technologies. Through interdisciplinary integration and innovation, shifting scar prevention and treatment strategies from passive anti-fibrosis to proactive promoting regeneration, guiding wounds toward true structural and functional regeneration, emerges as a promising path to overcome current limitations in scar management.