A multifaceted biomimetic periosteum with a lamellar architecture and osteogenic/angiogenic dual bioactivities

An artificial periosteum has emerged as an encouraging candidate for bone defect repair. Currently, it remains a great challenge to develop a multifaceted biomimetic periosteum integrating multifunctional features of bioactivities and unique mechanical properties. Here, we successfully fabricated an artificial periosteum (AP) composed of hierarchically assembled Mg-doped mineralized collagen microfibrils with a biomimetically rotated lamellar structure via a "multiscale cascade regulation" strategy combining multiple techniques such as molecular self-assembly, electrospinning, and pressure-driven fusion from molecular to macroscopic levels. The AP has excellent mechanical properties with an ultimate strength and a tensile modulus of 15.9 MPa and 1.1 GPa, respectively. The involvement of Mg-doped nano-hydroxyapatite endowed the AP with good osteogenic and angiogenic activities to promote osteogenic differentiation of bone marrow mesenchymal stem cells and human umbilical vein endothelial cell differentiation into capillary-like structures in vitro. In addition, the results of in vivo evaluations in a rat cranial bone defect model including micro-CT morphology, histological staining, and immunohistochemical analysis showed that Mg-doped mineralized collagen-based AP (MgMC@AP) significantly facilitated cranial bone regeneration and fast vascularization. Our findings suggest that the AP mimicked the composition, lamellar structure, mechanical properties, and biological activities of natural periosteum/lamellae, showing great promise for bone tissue regeneration.