Regenerative Engineering Approaches to Scar-Free Skin Regeneration

Skin is the largest organ of the human body. It is highly susceptible to injury. Typically, adult skin wounds heal via scar formation rather than regeneration. Thus, skin presents an excellent model to investigate mechanisms of scar formation to gain insight on regeneration. To date, there has been limited success in the development of therapeutics for scar-free regeneration through traditional approaches. Therefore, the development of a transdisciplinary approach to the investigation and development of therapeutics for scar-free regeneration is needed. The regenerative engineering approach involves the convergence of advanced materials science, stem cell science, physics, insights from developmental biology, and clinical translation. In this review, we describe some key aspects of scar-free skin regeneration from the perspectives of developmental biology. Then, we discuss multifaceted approaches such as the use of organism-derived tissues, cell-based strategies, and material-based strategies, towards scar-free skin regeneration. Regenerative engineering approaches using biomaterials combined with biological cues from physics and developmental biology hold significant potential for bringing new promising strategies to support scar-free skin regeneration. Skin is one of the largest and most vital organs. Severe damage to mammalian skin leads to failed healing and scar formation. There has been limited therapeutic success in creating scar-free skin regeneration. We believe the solution to scar-free skin regeneration in humans may lie in adopting a transdisciplinary approach to solve the problem. In this review, we first discuss the influence of biological cues on regeneration from studies using regeneration competent animals and fetus mammals. Next, current regenerative engineering approaches such as the use of organism-derived tissues, cell-based strategies, and material-based strategies are discussed. Finally, we provide future perspectives on achieving scar-free skin regeneration.