Biomedical Hydrogels Based on Oxidized Hyaluronic Acid and Carboxymethyl Chitosan Coordinated with Magnesium Ions

Abstract

Rapid hemostasis, oxidative stress resistance, and minimally invasive administration are crucial performance requirements for high-performance wound covering. Inspired by the dynamic remodeling properties of the native extracellular matrix, we fabricated a multifunctional injectable hydrogel through dynamic Schiff-base crosslinking between oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS), combined with magnesium ion (Mg2+) coordination. The effects of Mg2+ content on hydrogel properties were systematically investigated. The hydrogels gelled rapidly under physiological conditions and showed good injectability, self-healing behavior, and favorable adhesion to moist tissues. Notably, Mg2+ incorporation significantly enhanced hemostatic performance in a mouse tail amputation model, reducing blood loss from 391.7 mg to approximately 75 mg and shortening hemostasis time from 151.7 s to 50.3 s. The 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging efficiency reached approximately 80%, and the hydrogel effectively scavenged intracellular reactive oxygen species (ROS) without compromising cytocompatibility or fibroblast activity. This study presents a biomimetic and easily prepared hydrogel platform that integrates pro-coagulant activity, redox regulation, and on-demand injectability, showing translational potential as bioactive wound covering for bleeding control and oxidative microenvironment regulation.