Bioactive Topical Platforms for Pressure Ulcer Healing: Mechanisms and Translational Advances

Abstract

Pressure ulcers, also referred to as decubitus ulcers, are localized injuries to the skin and underlying tissues, typically occurring over bony prominences due to prolonged pressure, friction, or shear forces. Despite being largely preventable, they remain a significant global health concern, affecting approximately 10–15% of hospitalized patients and contributing to prolonged morbidity, elevated mortality risk, and increased healthcare expenditures. Traditional management strategies including frequent repositioning, debridement, infection control, and standard dressings often fail to fully address the complex pathophysiology involving chronic inflammation, oxidative stress, microbial colonization, and impaired angiogenesis. Recent advances in topical therapies incorporating bioactive compounds have shown considerable promise in enhancing pressure ulcer healing. Natural compounds such as phenolics (curcumin, resveratrol), terpenoids (asiaticoside), polysaccharides (chitosan, hyaluronic acid), and growth factor–mimetic peptides demonstrate potent antioxidant, anti-inflammatory, and pro-regenerative effects. Innovative delivery platforms—including nanocarriers, lipid-based systems, hydrogels, and stimuli-responsive polymers—improve solubility, stability, and targeted delivery of these labile compounds to the wound microenvironment. By modulating critical molecular pathways (e.g., NF-κB, MAPK, TGF-β, VEGF), these approaches promote collagen deposition, angiogenesis, and bacterial biofilm disruption. This review provides a comprehensive analysis of the mechanistic basis, formulation strategies, preclinical and clinical outcomes, and translational challenges associated with bioactive compound–loaded topical systems. Special emphasis is placed on smart delivery platforms and personalized wound care strategies, which collectively offer potential to improve healing outcomes and establish next-generation standards in chronic pressure ulcer management.