DLP 3D-Bioprinted Tissue-Engineered Bone with MPa-Level Mechanical Strength, Significant Osteogenesis and Angiogenesis, and Sequential Activation of Immune Response

Developing new material as a substitute for autogenous bone is pivotal for treating large-sized bone defects. In this study, a novel photocurable extracellular matrix hydrogel material composed of methacrylated bone-derived decellularized extracellular matrix (bdECM-MA), was synthesized using multi-physics-assisted combined decellularization (MPACD), side-chain biochemical modification (SCBM), and sterile freeze-drying (SFD). After mixing the bdECM-MA with silicon-substituted calcium phosphate (Si-CaP) and bone marrow mesenchymal stem cells (BMSCs), a new-generation tissue-engineered bone was fabricated by applying digital light processing (DLP) 3D bioprinting. This study provides in vitro confirmation that the tissue-engineered bone exhibits excellent osteogenesis and angiogenesis and has MPa-level mechanical strength. Moreover, the bone inhibits the p38-MAPK pathway, thereby regulating immune responses. A pioneering in vivo finding of this study is that the natural biomaterial-based tissue-engineered bone sequentially activates the immune response, causing a positive effect on bone regeneration and repair. Furthermore, owing to its excellent osteogenic, angiogenic, and immunomodulatory properties, the tissue-engineered bone significantly accelerates the healing of bone defects. This study provides a new research basis and an effective method for developing autogenous bone substitute materials and treating large-sized bone defects.