Defect‐Engineered Biomimetic Piezoelectric Nanocomposites With Enhanced ROS Production, Macrophage Re‐polarization, and Ca2+ Channel Activation for Therapy of MRSA‐Infected Wounds and Osteomyelitis

Antibiotic-resistant bacteria often cause lethal infections in both the surficial and deep organs of humans. Failure of antibiotics in resistant infections leads to more effective alternative therapies, like spatiotemporally controllable piezodynamic therapy (PZDT) with deep penetration. Currently, PZDT demands further investigation for improved treatment outcomes and the corresponding therapeutic mechanisms. Herein, a nanocomposite cloaked is reported with a biomimetic coating of TLR-upregulated macrophage membrane for targeted PZDT against MRSA-induced skin wound infection and osteomyelitis, representing surficial and deep infection models, respectively. To boost the therapeutic efficacy, crystal defect engineering is applied by impregnating Fe2+ into bismuth oxy-iodide nanosheets to increase the crystal defects. This results in a significantly higher piezoelectric coefficient than in previous reports, contributing to an amplified reactive oxygen species generation for bacterial killing. More importantly, the notable piezoelectric effect not only re-programs the macrophages into an anti-inflammatory M2 phenotype for accelerating bacterial wound healing but also stimulates the opening of the piezo-stimulated Ca2+ channels and boosts the differentiation of mesenchymal stem cells into osteoblasts for expediting bone tissue repair in osteomyelitis model. Moreover, the Fe-doping supplements T2-magnetic resonance imaging for real-time visualization of nanocomposite distribution. This theranostic system opens a new avenue for future treatment of drug-resistant bacteria-caused diseases.