Copper Nanocluster-Decorated Magnesium Silicate-Based Microneedle Enhances Antimicrobial Effects and Tissue Remodeling for Diabetic Wounds

Diabetic skin lesions, as one of the most common complications of diabetes, present chronic nonhealing wounds that face dual challenges of antibiotic-resistant bacteria threat and insufficient microenvironment regulation due to hyperglycemic conditions, bacterial infections, and multiple pathological factors (e.g., hypoxia and reactive oxygen species (ROS) accumulation and growth factor deficiency). This study develops a microneedle (MN) system integrated with copper nanocluster-decorated magnesium silicate nanoparticles (denoted as MS@Cu MNs), which enables efficient diabetic wound healing via a synergistic multimechanism strategy. Leveraging the unique enzyme-mimetic activity of copper nanoclusters (CuNCs) and the angiogenic properties of magnesium silicate nanoparticles (MS NPs), the engineered MS@Cu nanocomposites demonstrate: 1) broad-spectrum antibacterial efficacy (sterilization rate >99.9%), 2) microenvironment regulation via simultaneous hypoxia mitigation, ROS scavenging, and angiogenesis promotion, and 3) enhanced fibroblast proliferation and migration through PI3K-AKT signaling pathway activation. The MN system using γ-polyglutamic acid (γPGA) as a matrix exhibits both superior mechanical strength and excellent biodegradability. In vivo studies demonstrated accelerated closure of infected diabetic wounds in animal models, with histological analysis revealing robust mature collagen deposition and tissue regeneration. This study develops an integrated strategy for chronic diabetic wound management, combining potentiated antibacterial activity with targeted microenvironment remodeling.