The Osteoinduction Of Nell-1 On Spinal Fusion Model In Rats

Background: Spinal fusion is a very commonly performed procedure, which typically requires the use of bone graft material in order to obtain a solid arthrodesis. The traditional source for this bone graft has been the the patients own autogenous bone routinely taken from the iliac crest. Unfortunately the morbidity of harvesting the autogenous bone graft can be significant. Complications from this separate incision at the donor site include, permanent pain, infection, pelvic fracture, wound breakdown, and other significant problems that can add significant difficulties to the overall procedure. In addition, failure rates of the single level fusion utilizing autogenous bone graft can reach up to 35%. To reduce the need for autogenous bone graft, various osteoinductive growth factor-based therapies have been developed in an attempt to increase fusion rates and to eliminate the morbidity from the bone grafting procedure.Purpose: Our primary aim was to assess if direct adenoviral gene delivery with Nell-1 in a demineralized bone matrix (DBM) carrier can improve spinal fusion in a rat model. Nell-1 was first noted to be osteoinductive when abnormal bone formation in human craniosynostosis patients was associated with strong Nell-1 _expression.Methods: Two groups of 20 athymic rats underwent posterolateral intertransverse process spinal fusion at L4–L5 with implanted DBM carrier containing either adenovirus coding for Nell-1 (AdNell-1) or control, Lac Z (AdLacZ). The 20 rats were sacrificed at 6 weeks for evaluation of spinal fusion. All animals underwent X-ray at 2, 4, and 6 weeks, manual spine palpation, MicroCT and histology at 6 weeks.Results: After 6 weeks, direct application of adenoviral Nell-1 in a DBM carrier achieved significantly higher rates of spinal fusion over Lac Z: 80% Nell-1 versus 20% Lac Z by manual palpation and MicroCT,70% Nell-1 versus 20% Lac Z by histology. Histological assessment of bone quality and maturity revealed more mature, higher quality bone in all the Nell-1 treated specimens relative to Lac Z at 6 weeks. Conclusions: Direct application of adenoviral Nell-1 in a DBM carrier achieved significantly higher rates of spinal fusion over Lac Z controls at 6 weeks. Overall, Nell-1 may fulfill a current need for an osteoinductive factor. Nell-1, unlike BMPs, may act more specifically on further differentiated osteogenic lineage cells. And so on, micro CT should be considered as optimal standards of spinal fusion. It provides an invaluable method of judging both the magnitude and quality of the bony structure in an objective fashion.