Bifunctionalized hydrogels promote angiogenesis and osseointegration at the interface of three-dimensionally printed porous titanium scaffolds

The repair of severe bone defects is a great challenge in orthopedics. Although autologous bone grafting remains the gold standard for the treatment of bone defects, trauma, infection, and other problems associated with this procedure have limited its use in clinical practice. Three-dimensional (3D) printing technology is increasingly being used to produce advanced bone tissue engineering scaffolds with a bionic structure and optimal mechanical strength to promote bone regeneration. However, in addition to excellent osteogenic induction, angiogenesis is also essential for bone reconstruction. Therefore, we constructed a 3D-printed composite porous titanium scaffold system equipped with a thermosensitive collagen hydrogel loaded with vascular endothelial growth factor and bone morphogenetic protein-9 (VEGF/BMP-9). In vitro, the composite system showed great biocompatibility, and both human umbilical vein endothelial cells and bone marrow mesenchymal stem cells showed high viability when grown on the composite scaffold; In vivo, this system continuously provided angiogenic and osteogenic growth factors at the site of a lateral epicondyle osseous defect in a rabbit femur, thus promoting angiogenesis and osseointegration. These findings provide an important theoretical basis for the research and development of bioactive implant interfaces for patients with osteogenic defects.