Dynamic culturing of large cell-loaded PCL/gelatin methacryloyl scaffolds for bone critical size defect repair.

Due to the limited ability to self-repair, the regeneration of bone critical-sized defects (CSD) is a significant challenge. Bone tissue engineering scaffolds are considered promising candidates for CSD repair, but low cell infiltration efficiency and a lack of nutrients greatly restrict bone regeneration abilities. Herein, we developed a dynamic culturing of large biomimetic bone scaffolds, PCL/GelMA@cells that combining 3D printed polycaprolactone (PCL) multi-channel cylinder with gelatin methacryloyl (GelMA) encapsulated with bone marrow mesenchymal stem cells (BMSCs) and rat aortic endothelial cells (RAECs). A cell dynamic culture system was fabricated to simulate the dynamic microenvironment. Compared to static culturing, dynamic culturing proved to enhance the nutrient exchange within the large scaffold to promote the cells infiltration, growth, proliferation and induce osteogenic and angiogenic differentiation. Furthermore, a rat cranial CSD (D = 10 mm) repair model verified the accelerated vascular ingrowth and new bone formation with the implantation of dynamic culturing of PCL/GelMA@cells scaffold (∼10 times higher than Blank group), indicating the great potential of dynamical culturing of scaffolds for bone repair. In summary, the results highlight the significant advantages of the dynamical culturing of cell-loaded scaffolds for bone regeneration, offering a promising strategy for addressing critical size bone defects.