Regenerative Scar-Free Skin Wound Healing

Scar formation is a common consequence of skin injuries that lead to a wide range of adverse effects including physical deformities and psychological disorders. Studies demonstrate that mammalian fetal skin in early gestation is capable of regenerating itself after injury without any scar formation. A number of potential therapies have been developed to reduce scar formation in cutaneous wounds based on differences between the process of adult and fetal wound healing. The ideal approach to eliminate scar formation after skin injury is to use a pro-regenerative matrix along with growth factors and cell types that induce regeneration rather than repair. This work provides a comprehensive review of engineering approaches to scar-free wound healing with emphasis on the use of pro-regenerative biomaterials to minimize scar formation in skin injuries. Impact Statement Millions of people every year develop scars in response to skin injuries after surgery, trauma, or burns with significant undesired physical and psychological effects. This review provides an update on engineering strategies for scar-free wound healing and discusses the role of different cell types, growth factors, cytokines, and extracellular components in regenerative wound healing. The use of pro-regenerative matrices combined with engineered cells with less intrinsic potential for fibrogenesis is a promising strategy for achieving scar-free skin tissue regeneration.