Bone bioengineering for mandibular reconstruction

The reconstruction of critical-size bone defects following tumour resection or bone loss due to trauma is topical today and relates to the complexity of the treatment involved and poor healing outcomes. In bone bioengineering, the current trends are to explore novel methods of repairing these defects by using various bone substitutes. Various graft materials have been used for the restoration of these defects. A graft ideally needs to promote osteogenesis, osteoinduction and osteoconduction. The aim of this investigation was to assess the histological, radiographic and mechanical properties of the tissue regenerate following the application of tricalcium phosphate (TCP) scaffolding and recombinant human bone morphogenetic protein 7 (rhBMP-7) for the reconstruction of a critical-size osteoperiosteal mandibular continuity defect in the rabbit model. Highly purified and freeze dried recombinant human BMP-7 was used. It was produced by Chinese hamster ovary cells in culture and purified from the culture media. All the TCP samples had a porosity of 80% and average pore size of 100 – 500µm. For the rhBMP-7 loaded scaffolds; rhBMP-7 was reconstituted according to a recommended specification and 400ng were loaded by adsorption into the TCP scaffolds. Nine adult New Zealand white rabbits (3.0-4.0kg) were used for the planned study. In each case a unilateral osteoperiosteal mandibular body critical-size defect was created. In six cases the critical-size defect was filled with the rhBMP-7 on the TCP scaffolding, and in three cases the TCP was used alone. Assessments were made with plain radiographs at 0, 4, 8, and 12 weeks follow-up. Three months post-operatively the animals were sacrificed, the mandibles removed and the surgical sites were assessed with cone beam CT radiography, tested mechanically and analysed histologically. More bone regeneration was seen radiographically and histologically within the mandibles that received rhBMP-7 in the TCP, with evidence of both woven and lamellar bone formation. Union was obtained at the surgical site with no cartilage formation. The regenerated bone was confined to the area that had received the scaffold, with no calcification of the surrounding soft tissues. The TCP was also resorbed more completely in this experimental group. Very little bone was formed in the cases where the defect was filled with TCP alone. The mechanical properties of the regenerate in the group that received the rhBMP-7 and TCP were also significantly superior to those of the cases that received TCP alone. Histologically the overall mean of the percentage regenerated bone volume in the rhBMP-7 and TCP cases was 29.41% ± 6.25, while that for the TCP alone cases was 6.35% ± 3.08. The difference between the groups was statistically significant (p = 0.014). Mechanically the failure moments for the TCP alone cases were found to be very low (0-48mNm) while those for the rhBMP-7 and TCP cases were higher but there was considerable variation between the cases (55-2115mNm). Some of the cases in this group achieved failure moments comparable to normal untreated bone. In conclusion TCP scaffolding and rhBMP-7 can be used successfully for the reconstruction of critical-size mandibular defects in the rabbit model and TCP loaded with rhBMP-7 was significantly superior in its capacity for bone regeneration histologically when compared to TCP alone. The resultant bony regenerate could also at times have mechanical properties similar to those of natural bone. But due to the variability of the mechanical properties further investigations are required before clinical application