Biohybrid Bacteria as Living Nanofactories for Disrupting Diabetic Wound Pathological Cascade via Antimicrobial-Regenerative Coupling.

Abstract

Diabetic wound healing remains a formidable clinical challenge due to persistent biofilm formation, chronic inflammation, and excessive reactive oxygen species (ROS) accumulation. Current therapeutic approaches often lack synchronized antimicrobial-regenerative mechanisms and fail to provide sustained efficacy. Here, this work engineers a bioengineered living hydrogel system (BMB181@ALG) that leverages genetically modified Bacillus thuringiensis strain BMB181 as a melanin nanofactory, enabling in situ biosynthesis of multifunctional melanin nanoparticles (MNPs). Encapsulation within the hydrogel preserves bacterial metabolic activity, ensuring continuous MNPs production. These nanoparticles exhibit a dual-mode therapeutic action, including photothermal antibacterial activity under near-infrared irradiation for biofilm disruption and pathogen eradication, and ROS scavenging and antioxidant effects to modulate the inflammatory microenvironment. The sustained release of MNPs further promotes angiogenesis, enhances tissue regeneration, and dynamically regulates the diabetic wound microenvironment. Notably, the self-replenishing nature of this biohybrid system ensures long-term therapeutic efficacy, minimizing the need for frequent interventions. This study establishes a bacteria-driven therapeutic paradigm, demonstrating the translational potential of living microbial systems for next-generation precision wound management.