Glucose-responsive “sense-and-treat” microneedle patch for promoting diabetic chronic wound healing

Diabetic chronic wound, plagued by hyperglycemia-driven oxidative stress, bacterial infection, and impaired angiogenesis, represent a critical biomedical challenge with limited treatment options and dire clinical outcomes. Herein, a glucose-responsive “sense-and-treat” microneedle (MN) patch was designed for on-demand drug release and comprehensive diabetic chronic wound therapy. The multifunctional MN patch (denoted EAG-MNs patch) was fabricated from two functional precursors. Solution A was consisted of phenylboronic acid modified gelatin (PBA-Gel) complexed with epigallocatechin gallate (EGCG) through dynamic boronic ester bonds to provide glucose responsiveness. Solution B contained silver nanoparticle-decorated graphene oxide (AgGO) dispersed in hyaluronic acid (HA) to enable sustained antibacterial action. Upon exposure to hyperglycemic wound microenvironment, the boronic ester bonds undergo dissociation, triggering the rapid release of EGCG to scavenge reactive oxygen species, alleviate inflammation, and promote angiogenesis. Simultaneously, the dissolved AgGO component ensures robust and long-lasting antibacterial activity against prevalent pathogens. In an infected diabetic mouse wound model, the EAG-MNs patch significantly accelerated wound closure, reduced granulation tissue formation, enhanced collagen deposition and vascularization, and effectively eliminated bacterial infection compared to control groups. This intelligent MNs platform exemplifies a novel “sense-and-treat” paradigm for diabetic chronic wound management by actively sensing pathological cues and executing synergistic therapeutic actions, offering a promising versatile strategy for advanced wound care.