Cellular and Molecular Mechanisms of Wound Repair: From Biology to Therapeutic Innovation

Abstract

Wound repair preserves tissue integrity through four overlapping phases—hemostasis, inflammation, proliferation, and remodeling—coordinated by platelets, neutrophils, macrophages, fibroblasts, keratinocytes, endothelial cells, and stem/progenitor cells acting with growth factors, chemokines, extracellular matrix, and intracellular signaling. Disruption of these programs results in chronic non-healing wounds or fibrotic scarring. Recent work delineates microbial influences, epigenetic and transcriptomic regulation, and cellular heterogeneity resolved by single-cell and spatial omics. Concurrent advances in biomaterials, engineered scaffolds, stem cell-derived products, and genome-targeted approaches are enabling mechanism-based therapies. Persistent challenges include wound heterogeneity, systemic modifiers such as diabetes and aging, and safe, effective delivery of biologics. This review summarizes cellular and molecular mechanisms of cutaneous repair, outlines deviations that underlie pathological healing, and evaluates emerging concepts and translational strategies. Integrating classical models with contemporary insights supports the development of precision wound medicine and personalized interventions to improve outcomes and quality of life.