Achieving Clearance of Drug-Resistant Bacterial Infection and Rapid Cutaneous Wound Regeneration Using an ROS-Balancing-Engineered Heterojunction.

Abstract

Intractable infected microenvironments caused by drug-resistant bacteria stalls the normal course of wound healing. Sono-piezodynamic therapy (SPT) is harnessed to combat pathogenic bacteria, but the superabundant reactive oxygen species (ROS) generated during SPT inevitably provoke severe inflammatory response, hindering tissue regeneration. Consequently, an intelligent nanocatalytic membrane composed of poly(lactic-co-glycolic acid) (PLGA) and black phosphorus /V₂C MXene bio-heterojunctions (2D²-bioHJs) is devised. Under ultrasonication, 2D²-bioHJs effectively eliminate drug-resistant bacteria by disrupting metabolism and electron transport chain (ETC). When ultrasonication ceases, they enable the elimination of SPT-generated ROS. The 2D²-bioHJs act as a "lever" that effectively achieves a balance between ROS generation and annihilation, delivering both antibacterial and anti-inflammatory properties to the engineered membrane. More importantly, in vivo assays corroborate that the nanocatalytic membranes transform the stalled chronic wound environment into a regenerative one by eradicating the bacterial population, dampening the NF-κB inflammatory pathway and promoting angiogenesis. As envisaged, this work demonstrates a novel tactic to arm membranes with programmed antibacterial and anti-inflammatory effects to remedy refractory infected wounds from drug-fast bacteria.