Piezoelectric composites with BaTiO3 NPs as guiding membranes: reconstructing the bioelectric microenvironment for enhanced bone regeneration†

The occurrence of bone defects is often accompanied by the destruction of the inherent physiological and electrical microenvironments of bone tissue and the occurrence of a series of degenerative diseases. This study presents the development and characterization of chitosan–sodium alginate (CSSA) composite scaffolds reinforced with barium titanate (BTO) nanoparticles for use as barrier membranes in bone tissue regeneration. CSSA–BTO piezoelectric composite membranes were created by combining barium titanate nanoparticles with piezoelectric properties and the natural polymers carboxymethyl chitosan and sodium alginate as substrates. The physicochemical properties of the membranes such as tensile strength, solubility, degradation rate, and piezoelectricity were then determined. In vitro, we investigated the biocompatibility and osteogenic differentiation properties of each group of membranes. In vivo, we established a rat mandibular defect model and evaluated the potential of piezoelectric composite membranes for bone regeneration using histological staining and micro-CT imaging. The piezoelectric properties of the scaffolds were markedly enhanced with an increase in BaTiO₃ content, and the judicious incorporation of BaTiO₃ nanoparticles achieved a critical balance between degradation, early stability, and swelling properties. In vitro studies demonstrated that the CSSA–BTO composite scaffolds, particularly those with 5.0% BaTiO₃ content, promoted the viability, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs) under ultrasound stimulation. Additionally, these scaffolds supported angiogenesis in vitro, indicating their potential to enhance vascularization during bone repair. In vivo bone defect repair studies in a rat model confirmed the superior osteogenic and angiogenic capacities of the CSSA–BTO composite scaffolds with 5.0% BaTiO₃ content, leading to significant improvements in bone regeneration compared to control groups. Collectively, these findings indicate that the newly fabricated CSSA–5.0BTO composite piezoelectric film exhibits good physical and chemical properties and biocompatibility, and can effectively reconstruct the internal electrical microenvironment and promote bone regeneration.