Engineered decalcified bone matrix/barium titanate piezoelectric composite scaffolds for bone regeneration†

Healing of critical-sized bone defects (CSDs) remains a significant challenge in clinical treatment. Piezoelectric materials, which play a prominent role in the bioelectricity of bone homeostasis, have garnered increasing attention in bone regeneration. Under physiological conditions in bone tissue, the relative sliding of collagen fibers after mechanical deformation generates electrical signals, which form the intrinsic structural basis for the natural piezoelectric properties of blood vessels and bone tissue. In this study, we developed a collagen-decalcified bone matrix gel composite to mimic the piezoelectric mechanism of bone tissue and further incorporated barium titanate piezoelectric nanoparticles to enhance piezoelectricity, creating a collagen-decalcified bone matrix gel-barium titanate scaffold (COL/DBM/BT). This scaffold provides piezoelectric and osteoinductive properties to stimulate bone repair. Under ultrasound activation, in vitro and in vivo experiments revealed that the COL/DBM/BT piezoelectric scaffold significantly enhanced the migration, proliferation, adhesion, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), as well as the migration, adhesion, and vascularization of human umbilical vein endothelial cells (HUVECs). Notably, significant bone regeneration was observed in critical-sized mandibular bone defects in vivo. In summary, the ultrasound-assisted COL/DBM/BT scaffold creates a highly piezoelectric and osteoinductive microenvironment, promoting more efficient bone repair.