POLYPHENOLS AS NATURAL THERAPEUTICS IN WOUND HEALING: CURRENT PROGRESS AND FUTURE PERSPECTIVES

Abstract

Wound healing is a complex biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. Disruption of these coordinated phases, particularly in chronic conditions such as diabetes, obesity, vascular disorders, and aging, often results in delayed or non-healing wounds that remain a major clinical and economic burden worldwide. The increasing prevalence of antimicrobial resistance and the limitations of conventional wound therapies have intensified the search for safer, multifunctional, and naturally derived therapeutic agents. Among these, polyphenols have emerged as promising candidates due to their broad spectrum of biological activities, including antioxidant, anti-inflammatory, anti-microbial, angiogenic, and tissue regenerative properties. By modulating oxidative stress, inflammatory signaling pathways, extracellular matrix remodeling, collagen synthesis, and cellular proliferation, polyphenols actively promote tissue repair and accelerate wound closure. Numerous plant-derived polyphenols, including flavonoids, phenolic acids, stilbenes, lignans, and tannins, have demonstrated significant wound healing potential in both experimental and clinical studies. Despite their therapeutic promise, challenges such as poor bioavailability, limited stability, and rapid metabolism continue to hinder their clinical translation. Recent advances in biomaterial-assisted delivery systems, nanotechnology, and tissue engineering have provided new opportunities to overcome these limitations and enhance therapeutic efficacy. This review comprehensively discusses the current progress in polyphenol-based wound healing therapies, their molecular mechanisms, recent formulation strategies, and emerging clinical evidence while highlighting future perspectives for developing safe, effective, and sustainable natural therapeutics for wound management.