Peptides in wound healing: A comprehensive review of their roles, challenges, and hydrogel-based delivery systems

Chronic wounds are characterized by prolonged healing durations and disrupted progression through the normal phases of wound healing, hemostasis, inflammation, proliferation, re-epithelialization and remodeling. These wounds are often complicated by persistent infections and underlying conditions like diabetic mellitus, which hinders effective tissue regeneration. Traditional dressings provide limited therapeutic benefits; therefore, recent advancements in wound care have introduced peptide-based therapies that have gained considerable attention for their multifunctional roles in modulating wound repair. Peptides possess intrinsic antimicrobial, anti-inflammatory, angiogenic, and pro-regenerative properties, enabling them to regulate diverse cellular and molecular events across all stages of healing. This review highlights the mechanistic roles of therapeutic peptides in regulating and orchestrating wound healing applications. We further classify bioactive peptides derived from microbial, animal, and plant sources with documented roles in wound healing, and also address synthetic peptides engineered for wound healing. We discussed the peptide-based hydrogels, recent advancements in peptide-based hydrogels in wound healing, and also those hydrogels that are currently under investigation in clinical trials. The primary objective of this review is to provide the readers a detailed overview of the advancements in wound healing studies especially peptide incorporated hydrogels. See also the graphical abstract(Fig. 1).