Session IX - Basic Science
Composite Scaffolds of Tricalciumphosphate (TCP), Human Bone Marrow Stem Cells (hBMSC) and Adenoviral Gene Transfer of Bone Morphogenetic Protein Type 2 (AdBMP-2) in a Critical Size Femur Defect Model of the Rat
Purpose: Posttraumatic defects of bone substance frequently account for complications in the management of fractures. Autogenous cancellous bone graft is regarded as the best material available for this use, but the excision is associated with donor-side morbidity such as pain, fracture, and infection. Synthetic grafts such as TCP are considered as possible substitutes. Unlike autogenous cancellous bone, TCP is osteoconductive only, but not osteogenic or osteoinductive. In this study we investigate how composite scaffolds of TCP with osteogenic human stem cells and osteoinductive BMP-2 influence the process of fracture healing in a load-bearing critical size femur defect model of the rat.
Methods: Right femora of 80 rnu and lew rats were exposed and a critical size defect 4 mm long was generated. Femora were stabilized using a customized omega-shaped 1.4-mm K-wire. Animals were assigned to one of 7 groups: rnu, TCP (group 1); rnu, TCP + hBMSC (2); lew, control (3); lew, TCP (4); rnu, control (5), TCP + hBMSC + rhBMP-2 (6), and TCP + hBMSC + AdBMP-2 (7). A composite TCP implant containing the respective properties was introduced into the defect. Animals from control groups (3 and 5) were sham-operated with a K-wire only. Radiographs were taken in weeks 1, 3, 6, 9, and 12 after the procedure. Radiographs were analyzed for callus formation, remaining bone defect, and osteolysis.
Results: At the 6-week follow-up the critical size defect in 3 of 9 rats from group 7 (rnu, TCP, hBMSC, AdBMP-2) was bridged over by newly built bone tissue. In 1 of 10 rats from group 6 (rnu, TCP, hBMSC, rhBMP-2) the defect was bridged over, while in the remaining groups none of the defects were healed. These differences were not significant, however. Bone defects in group 1 to 7 measured 2.4, 0.8, 1.1, 1.6, 1.6, 1.6, and 2.2 mm, respectively, less than 1 week after the procedure. Differences among the groups were not significant. In many animals a widening of the marrow cavity, resembling osteolysis, was found. The mean osteolysis was significantly higher in group 1 (rnu, TCP; 4.6 mm) versus group 6 (rnu, TCP, rhBMP2; 2.7 mm), and in group 5 (rnu, control; 4.0 mm) versus group 3 (lew, control; 0.8 mm).
Conclusion/Significance: In this study, only rats with scaffolds including BMP-2 achieved a bridging of the fracture gap through newly built bone. Scaffolds with hBMSC that had been transfected with an adenoviral BMP-2 vector did better than those with the rhBMP2 protein, the higher success rate was not statistically significant in either one. Studies involving a higher number of animals, and probably a more stable type of fixation, are needed to deliver statistically sound data to endorse the use of adenoviral BMP-2 vectors in the treatment of bony defects.