Choline Phosphate Surface-Activated 3D-Printed Porous Titanium Scaffold Combined with Stem Cell Exosomes for Enhancing Bone Defects Repair

In recent decades, porous titanium (Ti) bone-engineered scaffolds have emerged as a promising biomaterial for bone defect repair due to their excellent biocompatibility and mechanical properties. However, the limited bioactivity on the surface of the porous scaffold hinders osteogenesis and osseointegration, thereby restricting its further application. In this study, we utilized surface-initiated atom transfer radical polymerization to prepare a zwitterionic poly[2-(methacryloyloxy)ethyl choline phosphate] (PMCP) modified bioactive coating on the surface of a 3D-printed porous Ti scaffold. Additionally, exosomes derived from bone mesenchymal stem cells (BMSCs) were introduced into the scaffold surface via specific interactions between choline phosphate and phosphatidylcholine (CP-PC) on exosomes. <i>In vitro</i> studies for ossification and transcriptome analysis have shown that the exosome bioactive coating on a Ti scaffold enhances the proliferation of BMSCs, their osteogenic activity, and the expression of osteogenic-related genes. Furthermore, <i>in vivo</i> study results from hard tissue sectioning and microcomputed tomography indicate that the bioactive Ti scaffold significantly promotes new bone formation after 4 and 12 weeks of implantation in rabbit femoral defects. Overall, this study showcases the potential of the exosome-based Ti scaffold to enhance osteogenic activity, offering a novel strategy for cell-free bone tissue regeneration with significant therapeutic implications.