Use of a bioactive scaffold for the repair of bone defects in a novel reproducible vertebral body defect model

Abstract

Bone defects in vertebral bodies (VB) usually occur after the reduction of fractures or are caused by bone disease. Besides the treatment of original disease, repair of the bone defect can restore the structure of VB and improve stabilization of the spine to protect the spinal cord nerves. To aid studies of the efficacy of bioengineering techniques for repair of VB, we developed a rat model with a critical size bone defect in VB. Air-motivated burrs were used to create two sizes of bone defect (2 × 3 × 1.5 mm; 2 × 3 × 3 mm) in the anterior part of VB in 6-month-old Fischer 344 rats. Quantitative CT analyses and histological assays demonstrated that neither defects self-repaired by 8 weeks post surgery. Moreover, the tendency of bone formation was monitored in the same animal by serial CT image evaluations, allowing us to demonstrate that there was significant bone growth during the 4- to 6-week period after the creation of the bone defect. We then implanted sintered poly(lactic-co-glycolic acid) (PLGA) microsphere scaffolds loaded with Matrigel with or without recombinant human bone morphogenetic protein 2 (rhBMP2; 2.0 µg rhBMP2/10 µL Matrigel/scaffold) into the bone defect (2 × 3 × 3 mm) in the VB. Bone formation was detected by quantitative analyses of serial CT images, which demonstrated bone growth in rats that received the rhBMP2 implant, in both surrounding areas and inside area of the scaffold. In addition to a rapid increase within 2 weeks of the operation, another significant bone formation period was found between 4 and 8 weeks after the implantation. By contrast, the control group that received the implant without rhBMP2 did not show similar bone formation tendencies. The results of CT analyses were confirmed by histological studies. This study suggests that a critical size bone defect of the anterior VB can be developed in a rat model. Characterization of this model demonstrated that 4 to 6 weeks after creation of the defect was a significant bone growth period for VB bone repair in rats. This animal model has further utility for the study of different biomaterials for VB bone repair. Implantation of a bioactive PLGA scaffold carrying rhBMP2 allowed more successful repair of the VB defect. Although further characterization studies are needed, the bioactive PLGA scaffold developed in this study will likely adapt easily to other in vivo osteogenesis applications.