Current Approaches Targeting the Wound Healing Phases to Attenuate Fibrosis and Scarring

Abstract

Cutaneous fibrosis results from suboptimal wound healing following significant tissue injury such as severe burns, trauma, and major surgeries. Pathologic skin fibrosis results in scars that are disfiguring, limit normal movement, and prevent patient recovery and reintegration into society. While various therapeutic strategies have been used to accelerate wound healing and decrease the incidence of scarring, recent studies have targeted the molecular regulators of each phase of wound healing, including the inflammatory, proliferative, and remodeling phases. Here, we reviewed the most recent literature elucidating molecular pathways that can be targeted to reduce fibrosis with a particular focus on post-burn scarring. Current research targeting inflammatory mediators, the epithelial to mesenchymal transition, and regulators of myofibroblast differentiation shows promising results. However, a multimodal approach addressing all three phases of wound healing may provide the best therapeutic outcome.

Keywords: EMT; burn; fibrosis; hypertrophic scarring; inflammation; macrophages; myofibroblasts; wound healing.

Figure 1

Regulators of wound healing and scarring. The temporal activation, overlap, and intensity of activation of each phase of wound healing are regulated by numerous molecular, biological, and mechanical factors. The figure indicates how each one of these factors is modulating wound healing towards an aggravation or an attenuation of fibrosis. Blue indicates activation, and pink indicates attenuation of fibrosis.