Innovative Topical Formulations Incorporating Bioactive Compounds for Enhanced Pressure Ulcer Management: Mechanisms, Efficacies, and Translational Advances

Background/Objectives: Pressure ulcers (PUs) are chronic wounds associated with sustained mechanical loading, ischemia–reperfusion injury, oxidative stress, dysregulated inflammation, microbial colonization, and impaired tissue repair. Bioactive compounds such as curcumin, resveratrol, asiaticoside, epigallocatechin gallate, and quercetin have attracted interest because of their reported antioxidant, anti-inflammatory, antimicrobial, pro-angiogenic, and extracellular-matrix-modulating activities. Their therapeutic development is frequently limited by poor aqueous solubility, chemical instability, degradation, and inadequate local retention. Advanced topical systems, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, hydrogels, electrospun systems, and stimuli-responsive formulations, have therefore been investigated to improve formulation stability, local deposition, wound-bed retention, and controlled release. Methods: This critical narrative review evaluates these approaches using an evidence-to-translation framework that distinguishes mechanistic and formulation evidence, indirect evidence from other wound models, pressure-ulcer-specific preclinical evidence, and human pressure-ulcer evidence. Particular attention is given to formulation performance, biological plausibility, model relevance, safety, reproducibility, manufacturing feasibility, regulatory considerations, and clinical readiness. Molecular pathways involving nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), nuclear factor erythroid 2-related factor 2 (Nrf2), and vascular endothelial growth factor (VEGF) are discussed according to the experimental contexts in which they were investigated, rather than assumed to represent universally demonstrated pressure-ulcer mechanisms. Results: The available evidence suggests that advanced formulations may improve selected pharmaceutical and biological endpoints; however, much of the literature remains mechanistic or preclinical, and findings from non-pressure-ulcer wound models should not be interpreted as direct evidence of clinical efficacy in pressure-ulcer treatment. Human pressure-ulcer evidence remains limited and heterogeneous. Conclusions: Future development should therefore prioritize pressure-ulcer-specific validation, standardized formulation and quality attributes, rigorous safety assessment, adequately powered clinical trials, patient-centred outcomes, and health-economic evaluation. This evidence-to-translation framework provides a basis for distinguishing promising experimental formulations from approaches that have progressed sufficiently toward clinical validation.