Friday, September 28, 2018 4:05 PM–5:05 PM abstracts: basic science of spinal fusion: 235. Peptide amphiphile nanoscaffolds potentiates the delivery of rh-BMP2 in a rabbit spine fusion model

BACKGROUND CONTEXT Recombinant human bone morphogenetic protein (rhBMP-2) is an effective biologic to mitigate pseudoarthrosis after spinal fusion surgery. However, supraphysiologic doses of rhBMP-2 can lead to significant complications, necessitating development of a product that can reduce its therapeutic dose. From our previous work, we have established peptide amphiphile (PA) nanofibers containing rhBMP-2 binding motifs as a potential material to achieve this aim in a rat proof-of-concept model. PURPOSE The purpose of this study was to assess and validate the efficacy of peptide amphiphile (PA) nanoscaffold containing a rhBMP-2 binding motif for spinal fusion in a more stringent animal model, with the intent of reducing the amount of exogenous growth factor necessary to achieve successful fusion. METHODS Female New Zealand white rabbits underwent bilateral PLF at L4-L5 utilizing sub-therapeutic doses of 30 µg or 60µg rhBMP-2 per animal (15 or 30µg per side). Rabbits received one of three delivery systems: ACS, PA/ACS, or PA/ACS particles. Spine fusion and bone regeneration were assessed using radiography, manual palpation, and microCT imaging. Manual palpation was performed by three blinded investigators using an established scoring system: 0=no fusion, 1=unilateral fusion, 2=bilateral fusion. Spines that average a score ≥1 were considered fused. One-way ANVOA with Tukey's post-hoc was used to evaluate for differences in fusion scoring among groups with continuous variables. RESULTS The delivery systems utilizing PA (PA/ACS or PA/collagen particles) achieved 100% fusion at both the 30µg or 60µg rhBMP-2 doses. This rate was significantly higher than the fusion rate observed using ACS alone at either the 30µg (0%, p CONCLUSIONS Although ACS is the only FDA approved rhBMP-2 delivery vehicle for spine fusion, its inefficient retention of the growth factor requires supraphysiologic doses to achieve consistent fusion. Our work demonstrates that a BMP-2-binding PA nanofiber scaffold used in conjunction with ACS or collagen particles can significantly enhance rhBMP-2 action, thereby reducing the necessary rhBMP-2 dose and potentially mitigating the side effects associated with high doses of the growth factor. Future studies will establish the lower limit of the rhBMP-2 dose required to elicit fusion in the rabbit model.