Chapter 50 - Cell and Molecular Biology of Wound Healing

Abstract

Wound healing is regulated by a complex, spatiotemporally controlled interplay between resident and circulating cells, extracellular ­matrix (ECM), chemical, biochemical, electrochemical, and mechanical signals from the ECM and soluble mediators. Wound healing starts with coagulation and haemostasis that stops the bleeding. Platelets in the clot are activated and release growth factors and cytokines that stimulate resident cells to start re-epithelialization, angiogenesis, and connective tissue repair. In addition, platelet-derived factors, activated complement, and bacterial products trigger an inflammatory reaction with neutrophil and macrophage influx to clear the ­bacteria. How effectively the inflammation is resolved will play a crucial role in determining the healing outcome. Fast re-­epithelialization that establishes the barrier function and neutrophil-macrophage interactions are important for this process. Initial influx of macrophages contains mainly cells that produce proinflammatory cytokines while the reparative macrophages that support granulation tissue formation, angiogenesis, and remodeling dominate the later stages of wound healing. Macrophages also stimulate the differentiation of resident cells, possibly fibroblasts and/or pericytes, to myofibroblasts, which produce matrix that, after remodeling, turns to either scar in skin or normal mucosal tissue in palatal oral mucosa. Current understanding about wound healing is largely based on data obtained from skin that does not always replicate oral mucosal wound healing. In general, however, the wound healing stages and key principles are shared among different tissues. Therefore, in this chapter we will discuss the general principles of wound healing and include information that is distinct to oral mucosal wound healing when relevant.