Cellular, biochemical, and clinical aspects of wound healing

Background: The response to tissue injury requires the symphonious interaction of immune cells, keratinocytes, fibroblasts, and endothelial cells, which unite to regenerate the damaged epithelium. Recent insights have elucidated the cellular and molecular mechanisms required for wound healing and have raised the prospect of novel therapeutic targets. Methods: Review of the pertinent literature. Results: The initial inflammatory response leads to the influx of macrophages and neutrophils, which release cytokines, growth factors, and nitric oxide, and induce nearby keratinocytes to migrate across the wounded epithelium. This process, known as re-epithelialization, requires integrin-mediated activation of Rho-GTPases. The subsequent influx of fibroblasts and endothelial cells results in the production of tissue stroma and formation of new blood vessels, which lead to the generation of functional tissue. Importantly, disease states associated with impaired or excessive wound healing can be attributed to defects in these responses, providing a rationale for the use of evidence-based biological therapies. Conclusion: The elucidation of the cellular and biochemical response to wound healing is essential for an understanding to the treatment of clinical conditions during which impaired healing is encountered.