Scarring in the skin after trauma, surgery, burn or sports injury is a major medical problem, often resulting in loss of function, restriction of tissue movement and adverse psychological effects. Whilst various studies have utilised a range of model systems that have increased our understanding of the pathways and processes underlying scar formation, they have typically not translated to the development of effective therapeutic approaches for scar management. Existing treatments are unreliable and unpredictable and there are no prescription drugs for the prevention or treatment of dermal scarring. As a consequence, scar improvement still remains an area of clear medical need. Here we describe the basic science of scar-free and scar-forming healing, the utility of pre-clinical model systems, their translation to humans, and our pioneering approach to the discovery and development of therapeutic approaches for the prophylactic improvement of scarring in man 1. Introduction Anything greater than a superficial injury to the skin of children and adults results in scar formation. Scarring is a major cause of physical and psychological morbidity [1–8]. Whilst various studies have utilised a range of model systems that have increased our understanding of the pathways and processes underlying scar formation, they have not been typically translated to the development of effective therapeutic approaches for scar management. This is evidenced by the fact that despite a number of potential treatment regimens, no single therapy is accepted universally as the standard of care [9–11]. As such, scar improvement still remains an area of clear medical need. Herein, we describe the basic science underlying scar-free and scar-forming healing, the utility and translation of preclinical model systems to humans, and our pioneering approach to the discovery and development of therapeutic approaches for the prophylactic improvement of scarring in man. 2. Scar-Free and Scar-Forming Healing Scarring and wound healing occur within a spectrum ranging from the ability to completely regenerate tissue in amphibians, through scar-free healing in embryos of different mammalian species, to scar-forming healing in children and adults. From an evolutionary perspective, the scarring response results in rapid replacement of missing tissue and, although suboptimal in terms of appearance and function, results in a reduction in the likelihood of infection and an increased likelihood of organism survival following injury. The ability of organisms to heal wounds without scar formation has
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