A Comprehensive Review on Scar Formation and Influencing Factors: Insights Into Mechanisms and Therapeutic Strategies Publisher



Peirovi B ; Ehteshami M S ; Rad Malekshahi M ; Ghanbari F ; Ghanbari H
Source: Archives of Dermatological Research Published:2026

Abstract

Scars are increasingly recognized as notable aesthetic and functional burdens that compromise self-image, psychosocial well-being, and, in certain cases, joint mobility. Consequently, interest in scar prevention and treatment strategies has gained considerable momentum. Scar formation is a multifactorial process regulated by a complex interplay of biochemical, biophysical, and cellular signals. Herein, we first set out the basic concepts of skin structure, wound-healing phases, and common scar types. This is followed by a discussion of less-explored yet critical regulators of scarring, including bioelectric signals, pH, mechanical forces, temperature, dermal water loss, reactive oxygen species, tissue oxygenation, glucose levels, inflammation, and key inflammatory cytokines. Subsequently, we synthesize conventional and emerging therapeutic strategies for scar prevention and management, with particular attention to advanced therapeutic approaches, including nano-based strategies, nanofat grafting, exosome-based therapies, stem-cell-based therapies, and microneedle-based systems. Finally, we outline current limitations in scar research and treatment, particularly the limited translational relevance of commonly used animal models and barriers to clinical and economic translation, and present future perspectives emphasizing personalized, regenerative, and advanced therapeutic strategies. Overall, this review underscores that scar formation results from the cooperative action of multiple regulatory factors, with transforming growth factor-β1 (TGF-β1) serving as a central mediator in this process. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2026.