A novel injectable ultrasound-powered bone-adhesive nanocomposite hydrogel was developed for the treatment of irregular bone defects. This hydrogel, composed of amino-modified barium titanate nanoparticles and a dynamically cross-linked biopolymer hydrogel network, exhibits high bone adhesion, injectability, and self-healing properties. The hydrogel's bone adhesive strength increased approximately threefold due to the inorganic-organic interaction between the nanoparticles and the hydrogel network. Under ultrasound irradiation, the hydrogel generated a controllable electrical output (-41.16 to 61.82 mV), significantly enhancing osteogenic effects in vitro and in vivo. Rat experiments confirmed accelerated bone healing in critical-size calvarial defects. Bioinformatics analysis revealed that the ultrasound-responsive hydrogel enhanced osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. The hydrogel's ability to generate electrical stimulation through piezoelectric effects offers a promising wireless solution for bone defect repair. The hydrogel's mechanical properties, self-healing behavior, and injectability were characterized through various tests, including rheological analysis, SEM, and CLSM. The hydrogel's piezoelectric response was confirmed through AFM and finite-element simulations. The hydrogel's output voltage under ultrasound stimulation was measured, showing a significant increase with higher ultrasound intensity. The hydrogel's in vitro adhesion properties were tested on porcine femur, demonstrating strong adhesion to bone tissue. The hydrogel's osteogenic potential was evaluated through ALP activity, protein expression, and RT-qPCR analysis, showing enhanced osteogenic differentiation. In vivo studies confirmed the hydrogel's degradation and biocompatibility in rats. The hydrogel's ability to generate electrical stimulation under ultrasound was validated through in vivo experiments, showing accelerated bone healing in critical-size calvarial defects. Transcriptome sequencing revealed that the hydrogel's electrical stimulation influenced gene expression related to osteogenic differentiation. The hydrogel's cell membrane potential and intracellular calcium ion concentration were measured, showing enhanced cellular responses. The hydrogel's mechanical properties and self-healing behavior were further analyzed, confirming its potential for bone tissue engineering. The study highlights the potential of ultrasound-powered piezoelectric hydrogels in treating irregular bone defects.A novel injectable ultrasound-powered bone-adhesive nanocomposite hydrogel was developed for the treatment of irregular bone defects. This hydrogel, composed of amino-modified barium titanate nanoparticles and a dynamically cross-linked biopolymer hydrogel network, exhibits high bone adhesion, injectability, and self-healing properties. The hydrogel's bone adhesive strength increased approximately threefold due to the inorganic-organic interaction between the nanoparticles and the hydrogel network. Under ultrasound irradiation, the hydrogel generated a controllable electrical output (-41.16 to 61.82 mV), significantly enhancing osteogenic effects in vitro and in vivo. Rat experiments confirmed accelerated bone healing in critical-size calvarial defects. Bioinformatics analysis revealed that the ultrasound-responsive hydrogel enhanced osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. The hydrogel's ability to generate electrical stimulation through piezoelectric effects offers a promising wireless solution for bone defect repair. The hydrogel's mechanical properties, self-healing behavior, and injectability were characterized through various tests, including rheological analysis, SEM, and CLSM. The hydrogel's piezoelectric response was confirmed through AFM and finite-element simulations. The hydrogel's output voltage under ultrasound stimulation was measured, showing a significant increase with higher ultrasound intensity. The hydrogel's in vitro adhesion properties were tested on porcine femur, demonstrating strong adhesion to bone tissue. The hydrogel's osteogenic potential was evaluated through ALP activity, protein expression, and RT-qPCR analysis, showing enhanced osteogenic differentiation. In vivo studies confirmed the hydrogel's degradation and biocompatibility in rats. The hydrogel's ability to generate electrical stimulation under ultrasound was validated through in vivo experiments, showing accelerated bone healing in critical-size calvarial defects. Transcriptome sequencing revealed that the hydrogel's electrical stimulation influenced gene expression related to osteogenic differentiation. The hydrogel's cell membrane potential and intracellular calcium ion concentration were measured, showing enhanced cellular responses. The hydrogel's mechanical properties and self-healing behavior were further analyzed, confirming its potential for bone tissue engineering. The study highlights the potential of ultrasound-powered piezoelectric hydrogels in treating irregular bone defects.