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

Abstract

To investigate the role of miR-31 genetically modified bone marrow mesenchymal stem cells (BMSCs) composited with porous β-tricalcium phosphate (β-TCP) scaffolds in repairing canine medial orbital wall defects. 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 β-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. 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 β-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. The use of BMSCs with suppression of miR-31 expression combined with β-TCP scaffolds can efficiently repair medial orbital wall defects in dogs.