Modified Fish‐Skin‐Collagen‐Based Hydrogels with Antioxidant and Antibacterial Functions for Diabetic Wound Healing

An innovative fish-skin-collagen-based hydrogel with self-healing and photothermal capabilities is developed. This modified hydrogel alleviates oxidative stress and bacterial infections in diabetic wounds through ferroptosis inhibition and bacterial iron homeostasis disruption. It synergistically combines these effects with collagen's inherent angiogenic and remodeling properties to effectively accelerate diabetic wound healing.

Abstract

Chronic wound management in diabetes represents a significant global medical challenge, primarily due to the complex microenvironment of diabetic wounds. Recently, fish-skin-collagen (Co)-based hydrogels have gained attention for treating skin wounds. However, their application in diabetic wounds has been restricted by their limited antibacterial properties, mechanical strength, and thermal stability. Here, a Co-based hydrogel (CFP) is developed, cross-linked via Co and a protocatechualdehyde–iron(III) Complex chelate (PCA@Fe) formed between protocatechualdehyde (PCA) and ferric ion (Fe³⁺). The CFP enhances its mechanical properties and thermal stability by forming Schiff base bonds between PCA@Fe and Co, while endowing itself with self-healing ability and photothermal effect. Co promotes angiogenesis and collagen remodeling, while PCA inhibits ferroptosis in cells and disrupts bacterial iron homeostasis, thereby suppressing the oxidative stress and bacterial infection in diabetic wounds. Furthermore, the photothermal effect synergizing with the disruption of bacterial iron homeostasis significantly reduces bacterial infections in diabetic wounds, thereby accelerating the healing process of chronic diabetic wounds.