Diabetic wound regeneration using peptide-modified hydrogels to target re-epithelialization

Significance Current treatments for diabetic chronic wounds fail to achieve effective therapeutic outcomes. The majority of these treatments focus on angiogenesis, but diabetes often involves endothelial dysfunction. A hallmark of regenerative wound healing is rapid, effective re-epithelialization. In this study, we present QHREDGS (glutamine-histidine-arginine-glutamic acid-aspartic acid-glycine-serine), a prosurvival peptide derived from angiopoietin-1, as a therapeutic candidate that targets re-epithelialization. Immobilized QHREDGS peptide promoted cell survival against hydrogen peroxide stress and collective cell migration of both normal and diabetic human keratinocytes in vitro. The clinical relevance was demonstrated further in type 2 diabetic mice: A single treatment with a low QHREDGS dose immobilized in chitosan–collagen was effective in promoting wound healing, and a single high-dose peptide treatment outperformed a clinically approved porous collagen dressing.