Acceleration of healing and improvement of scarring: from laboratory discovery to clinical practice

Acceleration of wound healing and improvement of scarring at skin graft donor sites and trauma or surgical lesions are important clinical goals in human and veterinary medicine. It has been discovered that wounds made on early mouse embryos heal quickly and perfectly, with no scars. The cellular and molecular differences between scar-free embryonic healing and scar-forming adult healing have been investigated. As a result, molecules have been identified which can be experimentally manipulated during adult healing, both to accelerate the process and to improve scarring. Some of these molecules represent pharmaceutical targets to which novel therapeutic agents have been developed. For example, embryonic wounds have high levels of TGFβ3 from endogenous keratinocytes and fibroblasts, but relatively low levels of TGFβ1 and TGFβ2 derived from degranulating platelets and inflammatory cells, by comparison to adult wounds. Therapeutically elevating the level of TGFβ3 allows adult rodent and porcine wounds to heal significantly faster and with improved scarring. These experimental findings have progressed into further studies in humans. A number of clinical trials with novel pharmaceuticals designed to accelerate healing and prevent scarring have been successfully completed, and further large patient-based trials are ongoing. These studies indicate that pharmaceutical treatment of healing wounds to accelerate the process (e.g. accelerated re-epithelialization of graft sites) or improve scarring may soon supplement the current surgical and device approaches to wound management.