Recent advances on anti-scarring properties of amniotic membrane: emerging strategies and clinical potentials in regenerative medicine.

Scarring remains an inevitable consequence of adult wound healing, often accompanied by functional, aesthetic, and psychological burdens. In contrast, fetal wound healing follows a fundamentally different trajectory, characterized by minimal inflammation, abundant hyaluronic acid, elevated type III collagen, and balanced matrix remodeling, culminating in regeneration without scar formation. This regenerative capacity is largely absent in adult tissues, which is the main incentive for understanding the pathophysiology of scarless healing phenotype to replicate such outcomes in adult tissues. The human amniotic membrane (hAM), as an embryogenic derivative, shares many structural and biochemical properties with fetal cutaneous tissue, positioning it as a promising biological tool to bridge adult wound healing toward a scarless, fetal-like outcome. hAM contains a rich milieu of growth factors, anti-inflammatory cytokines, and extracellular matrix components that support epithelialization, angiogenesis regulation, fibroblast modulation, and myofibroblast suppression. These effects are mediated through modulation of key signaling pathways including TGF-β/SMAD, PI3K/AKT, Wnt/β-catenin, and MAPK cascades; each central to the orchestration of fibrosis and regeneration. Furthermore, hAM's angio-modulatory behavior, antioxidant capacity, and context-dependent immune regulation contribute to a healing microenvironment that more closely mimics fetal conditions. In this review, we highlight the unique biology of fetal scarless healing which can be harnessed through the use of amniotic membrane-based therapies in adults. We highlight how the properties of hAM can help shift adult wound healing toward a more regenerative, less fibrotic outcome. We also examine different ways hAM is processed and applied in clinical settings and processing effects on anti-scar characteristic of hAM and discuss the main challenges that still need to be addressed, such as product standardization and optimizing treatment protocols, in a biomimetic way from scarless wound healing in embryo. Altogether, application of hAM presents a compelling and biologically sound approach to promote scarless wound healing in adult patients, a longstanding goal in regenerative medicine.