Significance: Scarring continues to present a significant clinical problem. Wound contraction leads to scarring and is mediated by myofibroblasts and contractile forces across the wound bed. Contracture formation can have a significant impact on the quality of life of the patient, particularly where function and appearance are affected. Recent Advances: Novel tissue-engineered matrices, cell-based therapies, and medicinal therapeutics have shown significant reduction in wound contraction in in-vivo models, particularly at early time points. These have been accompanied in many cases by reduced numbers of myofibroblasts, and in some by increased angiogenesis and improved neodermal architecture. Critical Issues: There are no animal models that replicate all aspects of wound healing as seen in patients. Therefore, information obtained from in vivo studies should be assessed critically. Additional studies, in particular those that seek to elucidate the mechanisms by which novel therapies reduce contraction, are needed to gain sufficient confidence to move into clinical testing. Future Directions: The use of knockout mouse models in particular has generated significant advances in knowledge of the mechanisms behind myofibroblast conversion and other factors involved in generating tension across the wound. Medicinal therapeutics and tissue-engineering approaches that seek to disrupt/alter these pathways hold much promise for future development and translation to clinical practice.
SCOPEFull-thickness wounds heal with scarring, due to the abnormal arrangement of de novo collagen fibres in the neodermis and contractile forces exerted on the wound environment and surrounding tissue. Scar formation can have a negative impact on the patient and continues to present a significant clinical challenge. In vivo models take into account the physiological response to injury and the complex interactions that occur during wound repair that cannot be replicated in vitro. This review summarizes recent in vivo studies that have demonstrated efficacy in reducing wound contraction in model organisms.
TRANSLATIONAL RELEVANCEThe demonstration of efficacy in vivo of a potential therapy to reduce wound contraction provides strong evidence of potential clinical efficacy. Further investigation and investment can then be undertaken to translate the novel therapy to early-stage clinical studies. In some cases, the manipulation, through the application of novel wound therapies, of the complex cascade of events leading to wound repair may have