Three-dimensional-printed ROS-scavenging and immunomodulatory hydrogel accelerates diabetic wound healing through synergistic microenvironment regulation.

From the paper

Abstract

The management of diabetic wounds remains clinically challenging, primarily owing to three interrelated pathological mechanisms: excessive accumulation of reactive oxygen species (ROS), dysregulated angiogenesis and sustained, non-resolving inflammation. To address these issues, we developed a multifunctional 3D-printed nanoparticle enhanced bionic skin (3D-NEBS) by integrating polydopamine-gallium-arginine nanoparticles (PDA-Ga-Arg) into a self-healing hydrogel matrix composed of oxidized Tremella fuciformis polysaccharide, carboxymethyl chitosan and fish gelatin. The resulting dressing exhibited mechanical adaptability, pH-responsive release, robust ROS-scavenging capacity and targeted immunomodulatory activity. In vitro, 3D-NEBS promoted M2 macrophage polarization, reduced inflammation, enhanced nitric oxide (NO) production and improved endothelial cell migration and tube formation. Broad-spectrum efficacy was confirmed, with significant growth inhibition observed against S. aureus and E. coli. In a diabetic rat model, 3D-NEBS achieved 92.79% ± 0.39% wound closure within 14 days, with enhanced collagen deposition and neovascularization. Transcriptomic analysis revealed upregulation of pathways related to collagen synthesis, antioxidant response and immune regulation. This study presents a synergistic hydrogel-nanoparticle platform with strong potential for diabetic wound repair.