Enhanced large segmental bone defect repair of bionic tissue-engineered bone grafts with 3D printed long bone-mimicking structures under micro-vibration stimulation

Large segmental bone defects pose a significant challenge in orthopedics, and bone tissue engineering has emerged as a promising strategy for addressing this problem. In this study, a digital light processing (DLP)-based 3D printing technique was used to fabricated a biphasic calcium phosphate (BCP) ceramic scaffold, which highly resembled the hierarchical structure of natural long bone, featuring osteon-like structure, along with vertically aligned Haversian canals and horizontally arranged Volkmann canals. These long bone-mimicking scaffolds, with tunable architecture and mechanical properties, were co-cultured with rabbit bone mesenchymal stem cells (BMSCs) under micro-vibration stimulation (MVS) to create bionic tissue-engineered bone grafts. In vitro cell experiment and in vivo nude mouse subcutaneous implantation suggested that compared to static culture, MVS significantly enhanced the osteogenic differentiation of BMSCs, stimulated their secretion to accelerate angiogenesis, and improved the survival of seeding cells. Moreover, these bionic bone grafts effectively promoted the in situ repair of critical-sized segmental radial defects and femoral diaphyseal defects in rabbits. Our findings demonstrate that the coupling of DLP-based 3D printing and MVS offers a biomimetic strategy to construct bionic bone grafts that closely resemble native long bones, offering a promising approach for repairing large segmental bone defects.