Oxygen-vacancy-engineered t-ZnO-CeO₂ Schottky junction enhanced infectious bone regeneration via photoelectric-photocatalytic effects-induced mitochondrial quality control.

Abstract

The repair of infectious bone defects presents formidable challenges due to complex aetiologies, inflammatory immune microenvironment and bacterial invasion. Tetrapod-like zinc oxide (t-ZnO) exhibit great potential in infectious bone defects due to its excellent photoelectrical and abundant active sites. Nevertheless, the rapid electron-hole recombination and inefficient near-infrared (NIR) absorption severely limit its repairing efficacy. Herein, Cerium dioxide (CeO₂) was grown in-situ on the t-ZnO via a hydrothermal process, forming an oxygen vacancy rich t-ZnO-CeO₂ Schottky junction, and subsequently incorporated into a Poly-L-lactic acid scaffold. On the one hand, oxygen vacancies introduce defect energy levels that lower the electronic transition barrier, boosting electron utilization and NIR absorption, thereby enhancing photoelectric performance. On the other hand, the work function difference between CeO₂ and t-ZnO creates a Schottky barrier at the interface, where generated electrons migrate into the built-in electric field, promoting electron-hole separation and photocatalytic activity. Results proved that the scaffold generated substantial ROS (64.8% yield), inducing bacterial cell death via GSH depletion and protein leakage, with efficacy reaching 89.4% against <i>E. coli</i> and 90.3% against <i>S. aureus</i>. Concurrently, it exerted immunomodulatory effects by promoting anti-inflammatory macrophage polarization, while also enhancing both autophagy and mitophagy in bone marrow mesenchymal stem cells (BMSCs), thereby breaking the vicious cycle between mtROS accumulation and mitochondrial damage, improved mitochondrial respiration. This photoelectric-photocatalytic effects-induced mitochondrial quality control drove BMSC osteogenesis. <i>In vivo</i>, the scaffold achieved both infection control and robust bone regeneration in rat calvarial defects by integrating antibacterial action, immune modulation, and osteo-induction.