Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P1. NF-κB inhibitor suppresses edema and promotes rhBMP-2-mediated bone formation in spinal fusion

Abstract

BACKGROUND CONTEXT Loading of absorbable collagen sponges (ACS) with recombinant human bone morphogenic protein-2 (rhBMP-2) has been successfully used to enhance bone formation and to induce spinal fusion. However, side effects, such as soft-tissue edema and inflammation, have been reported. NEMO binding domain peptide (NBD) inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of immune response. PURPOSE To investigate NBD's potential to reduce rhBMP-2-induced soft-tissue inflammation and to stimulate spinal fusion. STUDY DESIGN/SETTING To evaluate inflammation, ACS containing either high dose rhBMP-2, rhBMP-2+NBD, NBD only or buffer were only implanted into intramuscular fusion beds of 32 rats. To analyze new bone formation in the presence of NBD, posterolateral intertransverse lumbar fusion procedures were performed on 16 rats. ACS implants were loaded with rhBMP-2 or rhBMP-2+NBD. PATIENT SAMPLE No patients, animal study. OUTCOME MEASURES T2-weighted relaxation time (T2-RT), histological analysis (HE appropriate post hoc tests for multiple comparisons using Tukey's honestly significant was applied. p≤.05 was considered significant. RESULTS T2-RT values were increased in the BMP-2 group compared to BMP-2+NBD, NBD and ACS groups. No difference was detected between BMP-2+NBD versus NBD and ACS controls. Histological analysisof the implant-surrounding zones showed an increase in cellular activity in the BMP-2 group compared to BMP-2+NBD and controls. Presence of rhBMP-2 increased relative NF-κB binding and gene expression of inflammatory markers, interleukin (IL)1β, IL6, IL18, chemokine ligand (CCL)2 and CCL3 compared to controls. In the BMP-2+NBD group, cytokine expression was blocked. No differences were found between BMP-2+NBD and control groups. BMP-2+NBD resulted in a higher bone volume and reduced trabecular spacing compared to BMP-2, a higher number of levels fused, and similar structural properties of the bone tissue. CONCLUSIONS In summary, NBD reduces soft-tissue edema formation, reduces recruitment of inflammatory cells, diminishes NF-κB binding and blocks transcription of NF-κB-regulated cytokines in response to high-dose rhBMP-2 in rats. Furthermore, NBD stimulates bone formation in rhBMP-2-mediated spinal fusion, potentially through cross-talk of the NF-κB pathway with other pathways. The results of this study might provide the basis to develop new therapeutic approaches for spinal fusion using graft material with a combinatory administration of rhBMP-2 and NBD.