Transport disc distraction osteogenesis with recombinant human with recombinant humanwith recombinant human with recombinant human bone morphogenic protein-2 for large calvarial defect reconstruction

Abstract

Large calvarial defect can be developed by trauma, surgery or congenital anomalies. This condition can be dangerous to patients because brain is more susceptible to external impact than normal. To cover the calvarial defect, autologous bone or biomaterials was used conventionally, but complications including donor morbidity and infection were also reported. On the other hand, attempts using transport disc distraction osteogenesis (TDDO) to treat a calvarial defect has been made. But, till now, consistency and reliability of this method are lacking. In this study, we used an internal distractor, which was more stable than an external distractor, combined with humoral factor, recombinant human bone morphogenic protein-2 (rhBMP-2), to achieve sufficient bone formation using TDDO in the calvarial defect. BMP-2 is known to enhance consolidation, shorten the period of distraction, and eventually accelerate bone regeneration. Author compared the effect of mechanical factor (TDDO) and the combination of mechanical (TDDO) and humoral (rhBMP-2) factor.Fourteen mongrel dogs were divided into two groups, one was control (n = 6) and the other was experimental group (n = 8). The specially designed internal distraction device was applied. It had two guide rails which enhance stability of device and allowed drug delivery through cannulated rotator rod. After 5-day latency period, distraction was initiated. The distraction rate was 2 mm/day. It took 13 days for completion of whole defect length distraction. rhBMP-2 of 10 µg/day was injected during whole period of distraction. Consolidation period was 3 months. Area of osteogenesis was measured by three dimensional computed tomographic images, strength was assessed by compression strength measurements and histologic evaluation was conducted.Two dogs of the experimental group were excluded from this study due to infections. Therefore, 6 animals in the control group and 6 animals in the experimental group were compared. In the comparison of area of regeneration, the control group treated with only TDDO without rhBMP-2 showed 68.04 ± 18.07% of bone regeneration compared with original defect. On the contrary, the experimental group treated with TDDO and rhBMP-2 showed 94.64 ± 5.29% of bone regeneration. Average of area of osteogenesis was higher in rhBMP-2 treated group with statistical significance. (p < 0.01) Regenerated bone of the control group showed strength of 23.85 ± 6.19 N/mm2 in compression test and regenerated bone of the experimental group showed strength of 53.75 ± 18.66 N/mm2 in the same test. Comparison was performed with the ratio of regenerated bone strength to normal bone strength of each group. Regenerated bone of the experimental group showed increased strength with statistical significance. (p < 0.05) Histology of regenerated bone in the experimental group was more similar with normal cancellous bone compared to that of the control group. Osteoblastic rimming was more prominent in the regenerated bone of the experimental group and the number of osteoblasts was also increased compared to that of normal bone or the control group with statistical significance. (p < 0.01)TDDO with internal distraction device of delivering rhBMP-2 can enhance bone regeneration of large calvarial defect in dog model. Regenerated bone nearly covered large calvarial defect and strength of regenerated bone was similar with that of normal bone. These results indicate that the clinical human application of TDDO combined with rhBMP-2 is possible.