Advancing injectable hydrogels for wound treatment: targeted control of oxidative stress toward personalized regeneration.

Abstract

Wound injuries, including severe burns, diabetic foot ulcers, and chronic skin defects, remain a significant clinical burden due to their complexity, susceptibility to infection, and impaired healing, particularly in elderly individuals and patients with diabetes or vascular diseases. In these conditions, the wound healing process is disrupted by excessive oxidative stress, persistent inflammation, and microbial infection, ultimately leading to impaired tissue regeneration. These challenges highlight the urgent need for advanced wound care strategies capable of actively modulating the wound microenvironment to facilitate effective and timely healing. Among various hydrogel systems, injectable horseradish peroxidase (HRP)-catalyzed hydrogels have gained attention due to their biocompatibility, ease of application, tunable properties, ability to fill irregular wound geometries, versatility in material selection, and mild crosslinking conditions. These features make them promising candidates for multifunctional wound dressings in both acute and chronic wound management. This review provides a comprehensive overview of recent advancements in the development of injectable HRP-catalyzed hydrogels for wound treatment. We highlight key design strategies that confer multifunctional therapeutic capabilities, including hemostatic function, antibacterial activity, and reactive oxygen species-releasing and scavenging properties. Particular emphasis is placed on the incorporation of gasotransmitter-releasing components to regulate the wound microenvironment effectively. Furthermore, we discuss emerging strategies aimed at transforming these hydrogels into smart wound dressings with advanced functionalities, such as oxygen-releasing ability, electrical conductivity, and microbiome-modulating features. Finally, we emphasize the importance of developing scalable, safe, and personalized hydrogel systems capable of addressing the complex pathophysiology of chronic wounds and improving patient-specific wound care outcomes.