Posterolateral inter-transverse lumbar fusion in a mouse model

Abstract

BackgroundSpinal fusion is a common orthopaedic procedure that has been previously modeled using canine, lapine, and rodent subjects. Despite the increasing availability of genetically modified mouse strains, murine models have only been infrequently described.PurposeTo present an efficient and minimally traumatic procedure for achieving spinal fusion in a mouse model and determine the optimal rhBMP-2 dose to achieve sufficient fusion mass.MethodMicroCT reconstructions of the unfused mouse spine and human spine were compared to design a surgical approach. In phase 1, posterolateral lumbar spine fusion in the mouse was evaluated using 18 animals allocated to three experimental groups. Group 1 received decortication only (n = 3), Group 2 received 10 μg rhBMP-2 in a collagen sponge bilaterally (n = 6), and Group 3 received 10 μg rhBMP-2 + decortication (n = 9). The surgical technique was assessed for intra-operative safety, efficacy, access and reproducibility. Spines were harvested for analysis at 3 weeks (Groups 1, 2) and 1, 2, and 3 weeks (Group 3). In phase 2, a dose response study was carried out in an additional 18 animals with C57BL6 mice receiving sponges containing 0, 0.5, 1, 2.5, 5 μg of rhBMP-2 per sponge bilaterally.ResultsThe operative procedure via midline access was rapid and reproducible, and fusion of the murine articular processes was found to be analogous to the human procedure. Unlike reports from other species, decortication alone (Group 1) yielded no new bone formation. Addition of rhBMP-2 (Groups 2 and 3) yielded a significant bone mass that bridged the L4-L6 vertebrae. The subsequent dose response experiment revealed that 0.5 μg rhBMP-2 per sponge was sufficient to create a fusion mass.ConclusionWe describe a new approach for mouse lumbar spine fusion that is safe, efficient, and highly reproducible. The technique we employed is analogous to the human midline procedure and may be highly suitable for genetically modified mouse models.

Maximizing bone formation in posterior spine fusion using rhBMP‐2 and zoledronic acid in wild type and NF1 deficient mice

“…Posterolateral inter‐transverse spine fusion surgery was performed on 32 mice and, consistent with prior applications of the model, there were no cases of morbidity or mortality. Two surgeons working in tandem were able to complete an operation in ∼20 min.…”

“…Although an Nf1 +/− mouse model has been previously studied in the context of tibial fracture repair, investigation of spine fusion therapies has been limited by the unavailability of a suitable model of posterolateral spine fusion. We have previously described a novel approach for mouse lumbar spine fusion that is safe, efficient, highly reproducible, and analogous to contemporary human surgery . By applying this model to Nf1 +/− we have demonstrated that dual treatment with rhBMP‐2 and ZA is superior to treatment with rhBMP‐2 alone.…”

“…Such a system requires both a genetic model of NF1 deficiency as well as an established protocol for spine fusion surgery. We have previously described a novel protocol for spine fusion in mice which we have shown to be safe, reliable and reproducible . This model utilizes rhBMP‐2 delivered by surgically implanted collagen sponges to induce a posterolateral fusion.…”

Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation

“…For the ectopic bone formation model, uniform discs manufactured using a surgical tissue punch were surgically implanted into the hind limbs of mice using published methods (25). For the spine fusion model, twin porous collagen sponges (Medronic Australasia) were inserted parallel to the vertebrae as previously described (26). All mice were aged 8–12 weeks.…”

Preclinical models for orthopedic research and bone tissue engineering

“…A published method for inducing scoliosis is to encourage rodents to become bipedal by amputating their tail and elevating their food, however many researchers find this model difficult to ethically justify. Spinal fusion models are possible to create in rodents, however the differing anatomy of their spinal processes requires modification of the procedure to fuse adjacent articular processes rather than transverse processes . Such fusion models are commonly performed using both bone graft and BMPs.…”