Fabrication of barium titanate-loaded pH-responsive hydrogels for piezocatalytic antibacterial activity and...

Infected bone defects represent a persistent clinical challenge due to recurrent bacterial infection, inflammatory immune imbalance, and impaired osteogenesis. Conventional piezoelectric or antibacterial biomaterials often lack microenvironment responsiveness, leading to off-target effects, insufficient biosafety, and limited osteoimmune regulation. Here, a pH-responsive chitosan/β-glycerophosphate hydrogel loaded with barium titanate (BTO) nanoparticles is constructed for ultrasound-driven piezocatalytic antibacterial activity and osteoimmune regulation. The optimized hydrogel achieves rapid gelation, strong bone interfacial adhesion, favorable injectability, self-healing performance, and pH-sensitive swelling behavior, which selectively enhances the exposure and catalytic activity of BTO in acidic infectious microenvironments to realize on-demand reactive oxygen species (ROS) generation and reduce unnecessary oxidative damage. Under ultrasonic stimulation, BTO nanoparticles effectively produce hydroxyl radicals and singlet oxygen to eradicate both Gram-negative and Gram-positive bacteria without antibiotics or toxic metal components. Meanwhile, the composite hydrogel suppresses pro-inflammatory M1 macrophage polarization while promoting anti-inflammatory M2 polarization, and significantly enhances the osteogenic differentiation of mesenchymal stem cells. This intelligent design integrates pathology-triggered responsiveness, piezocatalytic sterilization, biocompatibility, and immune-osteogenic regulation, providing a novel and translatable strategy for efficient infected bone defect repair.