Topical Statin Therapy in Wound Healing: A Systemic Review of Therapeutic Outcomes

This systematic review evaluates the therapeutic potential of topical statin therapy in cutaneous wound healing across in vitro and in vivo animal and human studies. A PRIMSA-guided PubMed search identified 31 eligible studies evaluating simvastatin, atorvastatin, pravastatin, rosuvastatin, or mevastatin formulated a creams, ointments, hydrogels, nanoemulgels, liposomal gels, nanosponges, films, and advanced dressing for diabetic, excisional, burn, infected, pressure, vascular, and postoperative wounds. Across models, topical statins consistently accelerated wound closure and improved histological quality through convergent mechanisms, including enhanced angiogenesis and lymphoangiogenesis, promotion of re-epithelialization, modulation of collagen deposition and extracellular matrix remodelling, and attenuation of pro-inflammatory and infectious burden. Mechanistic studies demonstrated activation of intracellular signalling pathways, upregulation of vascular endothelial growth factor and CD31, macrophage polarization, restoration of epidermal growth factor receptor signalling via caveolin-1 and glucocorticoid receptor modulation, and context-dependent regulation of collagen I/III and myofibroblast activity. Clinical data, although limited, showed some initial promise in pressure ulcers and laparotomy wound healing. Safety profiles were generally favorable, with xerosis and increased transepidermal water loss reported only at higher simvastatin concentrations. Overall, topical statins represent a promising, mechanistically rational adjunct for wound management; however, heterogeneity in wound types, formulations, dosing, and comparators, together with sparse, small clinical trials, underscores the need for rigorously designed human studies to define optimal indication, concentrations, and delivery systems.