Targeting the myofibroblast to improve wound healing

Cutaneous wound healing is the physiological response to injury, and pathological healing continues to be one of the leading causes of morbidity and mortality. Patients suffering from diabetes, physical disablement, or vascular diseases are prone to exhibit poor healing and develop chronic wounds. Conversely, if tissue remodeling continues after successful healing, it develops into excessive connective tissue deformations that are visible as keloids and hypertrophic scars. Central effector cells in normal, insufficient, and excessive wound healing are extracellular matrix-producing and remodeling myofibroblasts. The local wound environment profoundly influences the healing success by controlling the activity of cells that are involved in the repair process. Hence, pharmacological as well as mechanical modulation of this environment bears significant potential to improve the outcome of wound healing. This chapter summarizes the factors leading to excessive healing and tissue contracture by myofibroblasts and reviews possible strategies on measures to improve the wound healing process. Emphasis will be placed on molecular targets and/or agents that have been shown to improve tissue repair in cell culture and animal models and that have entered into clinical trials.