Three-Dimensional-Printed Gelatin Methacrylate/Hydroxyapatite/Barium Titanate Piezoelectric Hydrogels for Bone Tissue Engineering

Bone defect repair remains a major clinical challenge. This study presents a novel strategy using a 3D-printed piezoelectric hydrogel scaffold─composed of gelatin methacrylate (GelMA, Gel), hydroxyapatite (HA), and barium titanate (BTO)─for functional bone tissue engineering. The GelMA/HA/BTO scaffold exhibited a well-defined porous structure, enhanced mechanical stability, and, crucially, reliable piezoelectric responsiveness. This key feature enables the material to convert external mechanical stimuli, such as low-intensity pulsed ultrasound (LIPUS), into endogenous electrical signals. In vitro, the scaffold promoted BMSC adhesion, proliferation, and osteogenic differentiation, with the performance significantly enhanced under LIPUS stimulation. Mechanistic insights revealed that the piezoelectric microenvironment remodeled the cellular miRNA expression profile, particularly upregulating osteogenesis-related miR-29b-3p and activating the AMPK signaling pathway. Collectively, this ultrasound-responsive, gene-regulating scaffold represents a promising approach for treating bone defects by leveraging piezoelectricity to actively stimulate bone regeneration.