BIOACTIVE PEPTIDES IN CUTANEOUS WOUND HEALING: MOLECULAR MECHANISMS, DELIVERY STRATEGIES, AND CLINICAL PERSPECTIVES

Abstract

Chronic non-healing wounds, including diabetic foot ulcers and pressure sores, represent a growing clinical challenge due to persistent inflammation, impaired neovascularisation, and resistance to conventional therapies. Bioactive peptides have recently emerged as a versatile class of wound-healing agents capable of targeting multiple phases of cutaneous repair. This mini-review synthesises current knowledge on the molecular mechanisms, classification, delivery strategies, and translational hurdles of these molecules. Peptides derived from marine organisms, food proteins, amphibian skin, and host-defence systems, as well as those generated by rational design, exhibit remarkable multifunctionality: they suppress NF-κB-driven inflammation, promote macrophage polarisation from the pro-inflammatory M1 to the reparative M2 phenotype, stimulate angiogenesis via VEGF up regulation, and activate PI3K/Akt/mTOR and TGF-β/Smad cascades to drive keratinocyte and fibroblast proliferation, migration, and collagen deposition. However, clinical translation is severely constrained by rapid proteolytic degradation, short plasma half-life, and lack of robust human data. Recent advances in delivery systems, including stimuli-responsive self-assembling hydrogels, nanoparticles, and molecular engineering strategies such as cyclisation and D-amino acid substitution, offer promising solutions to these pharmacokinetic limitations. Nonetheless, challenges related to manufacturing scalability, regulatory approval, and incomplete understanding of structure–activity relationships persist. Further progress will depend on integrated approaches combining rational peptide design, innovative biomaterials, and rigorous clinical evaluation to transform the considerable preclinical promise of bioactive peptides into effective, accessible wound therapeutics.