A Structured Scaffold Featuring Biomimetic Heterogeneous Architecture for the Regeneration of Critical-Size Bone Defects

The regeneration of critical-size bone defects on long bones has remained a significant challenge because of the complex anatomical structure and vascular network. In such circumstances, current biomaterial forms with homogeneous structure and function can hardly satisfy the need for both osteogenesis and angiogenesis. In the current study, a heterogeneous biomimetic structured scaffold was constructed with the help of a 3D printed mold to simultaneously mimic the outer/inner periosteum and intermediate bone matrix of a natural long bone. Because of the reinforcement via modified mesoporous bioactive glass nanoparticles (MBGNs), enhanced structural stability and adequate osteogenic capacity could be achieved for the intermediate layer of this scaffold. Conversely, GelMA incorporated with VEGF-loaded liposome exhibiting controlled release of the angiogenic factor was applied to the inner and outer layers of the scaffold. The resulting heterogeneous structured scaffold was shown to successfully guide bone regeneration and restoration of the natural bone anatomic structure, rendering it a promising candidate for future orthopedic clinical studies.