Living Therapeutic Microneedles Integrated with Built-In Metabolic Engines for Autonomous Diabetic Wound Management

Chronic diabetic wounds remain one of the most intractable complications of diabetes, demanding therapeutic strategies that can simultaneously regulate local glucose levels, combat persistent infections, and promote angiogenesis. Here, we engineer a living-therapeutic microneedle system that integrates metabolically active probiotics with a pH-responsive carboxymethyl chitosan/l-arginine matrix to autonomously orchestrate wound microenvironment remodeling. Leveraging the unique metabolic capacity of <i>Lactobacillus reuteri</i>, our system rapidly and sustainably reduces local hyperglycemia (84.8% reduction over 48 h) while generating broad-spectrum antimicrobial reuterin in situ, circumventing drawbacks of conventional antibiotics. In parallel, a microneedle matrix scavenges reactive oxygen species and drives robust angiogenesis. In infected diabetic mice, a single administration can accelerate wound closure by 7.3-fold, eliminate pathogens via synergistic bactericidal and nutrient-competition mechanisms, and restore normoglycemia without rebound. This synergistic "metabolic engine-microenvironment modulation" paradigm addresses key barriers in diabetic wound healing and offers a scalable platform for living microbe-material therapeutics in chronic disease management.