Multifunctional chito-oligosaccharide-and deferoxamine-modified GelMA-OHA hydrogel dressing with antibacterial, antioxidant, and pro-angiogenic activities for infected wound healing

Abstract

Infected wounds resist healing due to multidrug-resistant bacterial colonization and persistent inflammation, which render conventional antibiotic therapies largely ineffective. Consequently, non-antibiotic strategies that coordinate infection control with tissue regeneration are urgently required. We design a dual-crosslinked hydrogel composed of gelatin methacryloyl (GelMA) and oxidized hyaluronic acid (OHA), further functionalized with chitosan oligosaccharide (COS) and deferoxamine (DFO), yielding the multifunctional GOCD hydrogel. Dynamic Schiff base linkages confer controlled release of COS and DFO, enabling coordinated antibacterial, antioxidant, and pro-regenerative activities. Experiments show that the GOCD hydrogel achieves an antibacterial rate of 88.03% against methicillin-resistant Staphylococcus aureus (MRSA). Meanwhile, its DPPH and ABTS radical-scavenging rates are 77.92% and 89.44%, respectively. Moreover, the hydrogel upregulates Nrf2 expression, effectively scavenges intracellular reactive oxygen species (ROS), and significantly enhances the migration of human umbilical vein endothelial cells (HUVECs) and tube-forming capacity. In infected rat wounds, GOCD hydrogel treatment leads to a wound closure rate of 92.97% by day 14, accompanied by organized collagen deposition and a significant increase in vascular density, with no observed systemic toxicity. Collectively, the GOCD hydrogel constitutes a safe and effective non-antibiotic healing platform that coordinates antibacterial, antioxidant, and pro-angiogenic functions for the repair of infected wounds.