Natural bone collagen scaffold combined with autologous enriched bone marrow cells for induction of osteogenesis in an ovine spinal fusion model

Autologous bone graft, the standard of bone grafting in achieving spinal fusion, is associated with several limitations and complications. The use of bone marrow cells (BMCs) as a potential cell source for spinal fusion, combined with a suitable scaffold to promote bone formation, may be a better choice. The aims of this study were to evaluate the efficacy of natural bone collagen scaffold (NBCS) combined with autologous-enriched BMCs for induction of osteogenesis in vitro and in vivo. Ovine-enriched BMCs were co-cultured with NBCS for 1, 2, 3, and 4 weeks to investigate whether NBCS would support the population expansion and differentiation of enriched BMCs. Using an ovine interbody fusion model, NBCS seeded with autologous enriched BMCs was implanted into the lumbar disc space. Fusion outcomes were compared with the use of the autograft, NBCS without BMCs, and BMCs without NBCS. In vitro results demonstrated that NBCS facilitated the population expansion and differentiation of ovine-enriched BMCs, promoting the expression of collagen type I and the formation of a mineralized matrix. The use of NBCS combined with enriched BMCs in vivo enhanced the spinal fusion rate (6 of 6 at 10 week) (p<0.05), the biomechanical stiffness of fusion masses, and bone volume at the fusion site (p<0.05). Histological findings also revealed that a combination of NBCS and BMCs induced new bone formation that integrated well with host bone tissue. In conclusion, NBCS is an effective scaffold that supports ovine-enriched BMCs. The combination of NBCS and BMCs may be a useful alternative for autograft in induction of spinal fusion.