Review
Peptides in wound healing: A comprehensive review of their roles, challenges, and hydrogel-based delivery systems
Rafl M Kamil et al. EXCLI J. 2025.
Abstract
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).
Keywords: biomaterials; hydrogels; peptides; tissue regeneration; wound healing.
Copyright © 2025 Kamil et al.
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Conflict of interest statement
The authors declare that there are no commercial or financial relationships that could be construed as a potential conflict of interest in the preparation and publication of this review.
Figures Table 1. Classification of wounds based on different wound characteristics Table 2. Bioactive peptides derived from microbial, animal, and plant sources with documented roles in wound healing Table 3. Synthetic peptides engineered for wound healing applications Table 4. Wound-healing peptides with details of the studies replicated by independent research groups Table 5. List of commercial peptide-based hydrogels in the current market Table 6. Recent advances on peptides as tissue regenerative wound healing agents for skin conditions Table 7. List of peptide hydrogels that are currently under investigation in clinical trials Figure 1. Graphical abstract Figure 2. The illustration shows the total healthcare expenditure on wound care (in billion USD per year) and the prevalence of wounds (per 100,000 population) across selected countries (Ref: Wounds Australia, 2024; Queen and Harding, 2024; Ruiz and Lima, 2022; Queen and Botros, 2024; Hopkins et al., 2015; Queen and Harding, 2023; Jiang et al., 2020; Healthcare-in-Europe, 2008; Heyer et al., 2016; Morat and Ajemi, 2024; Iyun et al., 2024; Kharrati, 2024; Sharma et al., 2024; Sen, 2021). Figure 3. Schematic representation of the five sequential phases of wound healing and the associated roles of key peptides where (a) Hemostasis phase that is characterized by platelet aggregation and vasoconstriction mediated by secreted molecules including ADP, PDGF, TXA2, TGF-β, and 5-HT; Here in peptides such as LL-37 can induce further clot formation. (b) Inflammatory phase were neutrophils and macrophages clear pathogens. Peptides such as Thymosin β4 can facilitate macrophage transition. (c) Proliferative phase were fibroblasts, myofibroblasts, and pericytes coordinate ECM deposition and angiogenesis. Peptides such as Cathelicidin can support this phase. (d) Re-epithelialization phase in which keratinocyte migration and proliferation occur, and it's driven by MMPs and growth factors (EGF, HB-EGF, FGF-7), this can be enhanced by peptides such LL-37 and Thymosin β4. Lastly, (e) Remodeling phase where collagen maturation and tissue contraction take place, and it's regulated by MMPs and myofibroblast apoptosis which can be facilitate by peptides such as Thymosin β4. (VEGF, Vascular Endothelial Growth Factor; TGF-β, Transforming Growth Factor-beta; MMP, Matrix Metalloproteinase; EGFR, Epidermal Growth Factor Receptor). Figure 4. A schematic illustration that shows the preparation and application of peptide-based hydrogels for wound healing.
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