A Hierarchical 3D Graft Printed with Nanoink for Functional Craniofacial Bone Restoration

An ideal craniofacial bone repair graft shall not only focus on the repair ability but also the regeneration of natural architecture with occlusal loads-related function restoration. However, such functional bone tissue engineering scaffold has rarely been reported. Herein, a hierarchical 3D graft is proposed for rebuilding craniofacial bone with both natural structure and healthy biofunction reconstruction. Inspired by the bone healing process, an organic-inorganic nanoink with ultrasmall calcium phosphate oligomers and bone morphogenetic protein-2 incorporated is developed for spatiotemporal guidance of new bone. Based on such homogeneous nanoink, a biomimetic graft, including a cortical layer containing Haversian system, and a cancellous layer featured with triply periodic minimum surface macrostructures, is fabricated via projection-based 3D printing method, and the layers are loaded with distinct concentrations of bioactive factors for regenerating new bone with gradient density. The graft exhibits excellent osteogenic and angiogenic potential in vitro, and accelerates revascularization and reconstructs neo-bone with original morphology in vivo. Benefiting from such natural architecture, loading force is widely transferred with reduced stress concentration around the inserted dental implant. Taken from native physiochemical and structural cues, this wstudy provides a novel strategy for functional tissue engineering through designing function-oriented biomaterials.