Peptide-Based Composite Hydrogels Loaded With Chlorogenic Acid for Diabetic Wound Healing

Abstract

Chlorogenic acid (CGA) aids diabetic wound healing via antioxidant, antibacterial, and pro-migration effects, but poor stability and low membrane permeability limit its use in chronic diabetes. Therefore, we employed a one-pot method to mix naphthalene-modified diphenylalanine (FF) and hyaluronic acid (HA) to prepare an injectable composite hydrogel capable of delivering CGA to inflamed wounds and enabling sustained-release drug delivery, thereby promoting the healing of diabetic wounds. We evaluated it through the rheological and morphological properties, as well as the in vitro biocompatibility of the hydrogel. Structurally, the hydrogel exhibits a uniform nanofiber network, conferring enhanced mechanical strength and stable drug-loading capacity. In a mouse wound model, it reduced wound area to 7.99% ± 0.73% after 12 days of treatment, with increased granulation tissue, collagen deposition, and microvascular density compared with the normal saline group. Collectively, these findings indicate that the peptide-based composite hydrogel promotes local angiogenesis and vascular maturation, thereby accelerating the healing process of chronic diabetic wounds. This system represents a promising strategy for the development of bioactive wound dressings. Nevertheless, the underlying molecular mechanisms remain to be fully elucidated, and further validation in large animal models is required prior to clinical translation.

Keywords

chlorogenic acid / diabetic wound healing / hydrogel / peptide

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2026 The Author(s). MedComm - Future Medicine published by John Wiley & Sons Australia, Ltd on behalf of Sichuan International Medical Exchange & Promotion Association (SCIMEA).