3D Printing of Dual-cell Delivery Titanium Alloy Scaffolds for Improving Osseointegration Through Enhancing Angiogenesis and Osteogenesis

Abstract BACKGROUND: The repair of large bone defects is a great challenge for orthopedics. Although the development of three-dimensional (3D) printed metal implants with optimized the pore structure have effectively promoted the osseointegration. However, due to the biological inertia of titanium alloy (Ti6Al4V) surface and the neglect of angiogenesis, some patients still suffer from postoperative complications such as dislocation or loosening of the prosthesis. METHODS: The purpose of this study was to construct 3D printed porous Ti6Al4V scaffolds filled with bone marrow mesenchymal stem cells (BMSC) and endothelial progenitor cells (EPC) loaded hydrogel and evaluate the effects of this composite implants on angiogenesis and osteogenesis, thus promoting osseointegration. RESULTS: The porosity and pore size of prepared 3D printed porous Ti6Al4V scaffolds were 69.2 ± 0.9 % and 593.4±16.9 μm, respectively, which parameters were beneficial to blood vessel formation and bone ingrowth. The BMSC and EPC filled into the scaffold pores after being encapsulated by hydrogels can maintain high viability. As a cells containing composite implant, BMSC and EPC loaded hydrogel incorporated into 3D printed porous Ti6Al4V scaffolds enhancing angiogenesis and osteogenesis to repair bone defects efficiently. At the transcriptional level, the composite implant up-regulated the expression levels of the osteogenesis-related genes alkaline phosphatase (ALP) and osteocalcin (OCN), and angiogenesis-related genes hypoxia-inducible factor 1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF). CONCLUSION: Overall, the strategy of loading porous Ti6Al4V scaffolds to incorporate cells is a promising treatment for improving osseointegration.