Repair of Canine Medial Orbital Bone Defects With miR-31-Modified Bone Marrow Mesenchymal Stem Cells

PURPOSE. To investigate the role of miR-31 genetically modified bone marrow mesenchymal stem cells (BMSCs) composited with porous beta-tricalcium phosphate (beta-TCP) scaffolds in repairing canine medial orbital wall defects. METHODS. A circular bone defect (10 mm in diameter) was created on the canine medial orbital wall. After canine BMSCs were isolated and transfected with lentiviral vectors encoding miR-31, anti-miR-31 (anti-miR), and negative control (miR-Neg) in vitro, they were seeded onto porous beta-TCP scaffolds and implanted to repair the orbital defects. Spiral computed tomography (CT) scans were conducted at 4 and 16 weeks after surgery. Micro-CT and histological analysis were performed at 16 weeks after surgery. The results were analyzed to evaluate the extent of bone repair. RESULTS. Examination with CT revealed good recovery in the anti-miR group at 16 weeks after surgery. In addition, the micro-CT analysis showed that the bone mineral density and new bone volume increased in the anti-miR group and decreased in the miR-31 group compared with that in the miR-Neg group. Histologic analysis confirmed that the formation of new bone and extent of beta-TCP degradation were enhanced in the anti- miR and attenuated in the miR-31 group. In situ hybridization and immunohistochemical analysis further confirmed the micro-CT findings. CONCLUSIONS. The use of BMSCs with suppression of miR-31 expression combined with beta-TCP scaffolds can efficiently repair medial orbital wall defects in dogs.