Polyhedron-Like Biomaterials for Innervated and Vascularized Bone Regeneration.

Neural-vascular networks are densely distributed through periosteum, cortical bone and cancellous bone, which is of great significance for bone regeneration and remodeling. Although significant progresses have been made in bone tissue engineering, ineffective bone regeneration and delayed osteointegration still remains an issue due to the ignorance of intrabony nerves and blood vessels. Herein, inspired by space-filling polyhedron with open architectures, polyhedron-like scaffolds with spatial topologies were prepared via 3D printing technology to mimic the meshwork structure of cancellous bone. Benefiting from its spatial topologies, polyhedron-like scaffolds greatly promoted the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) via activating PI3K-Akt signals, and exhibited satisfactory performance on angiogenesis and neurogenesis. Computational fluid dynamic (CFD) simulation elucidated that polyhedron-like scaffolds had a relatively lower area-weighted average static pressure, which is beneficial to osteogenesis. Furthermore, in vivo experiments further demonstrated that polyhedron-like scaffolds obviously promoted bone formation and osteointegration, as well as inducing vascularization and ingrowth of nerves, leading to innervated and vascularized bone regeneration. Taken together, this work offers a promising approach for fabricating multifunctional scaffolds without additional exogenous seeding cells and growth factors, which holds great potential for functional tissue regeneration and further clinical translation. This article is protected by copyright. All rights reserved.