A Pre-Set Calcium Sulfate/Hydroxyapatite Biomaterial as an Antibiotic-Eluting Bone Extender and a Carrier for BMP-2: A Pilot Study in a Rabbit Posterolateral Spinal Fusion Model

Synthetic biomaterials used as bone graft extenders (BGE) in spinal fusion surgery can supplement but do not replace autologous bone. This pilot study evaluated a calcium sulfate/hydroxyapatite (CaS/HA) material as an antibiotic-eluting BGE and a carrier for bone morphogenetic protein-2 (BMP-2) in a rabbit posterolateral lumbar (L4-L5) spinal fusion model (PLF). Pre-set CaS/HA beads were loaded with tobramycin (TOB) and tested for in vitro antibiotic release and antibacterial activity against <i>Staphylococcus aureus</i>. For the in vivo PLF study, CaS/HA beads were used in two treatment strategies: (1) CaS/HA + TOB + autograft (left side) and (2) CaS/HA + BMP-2 (right side). Serum levels of TOB were quantified and spinal fusion was evaluated after 12 weeks. TOB exhibited a rapid initial release, followed by a decline below detectable levels after 6 h in vitro and 48 h in vivo. TOB-loaded CaS/HA beads demonstrated in vitro antibacterial activity for 19 days. In the PLF study, 5/6 and 6/6 specimens were fused radiologically in the TOB and BMP groups, respectively, and 100% using mechanical testing. Micro-CT analysis showed no significant difference in bone volume between the TOB and BMP-2 groups (364 ± 84 vs. 479 ± 95 mm³). Histology verified continuous bone bridging in both groups. Our in vitro findings indicate that locally added TOB could protect the CaS/HA material from bacterial colonization and did not adversely impact the CaS/HA material negatively to act as BGE. The addition of low-dose BMP-2 to the CaS/HA material proved effective in building bone without the need to harvest autologous bone. In summary, this pilot PLF study demonstrates that the tested CaS/HA material combined with BMP-2 could replace autologous bone harvesting in spinal fusion surgery. Addition of TOB could potentially protect the material from bacterial colonization during the early post-operative period but further studies in infection models are warranted.