89. Interbody fusion using a new controlled release BMP-2 matrix

BACKGROUND CONTEXT Lumber intervertebral fusion is essential for restoring segmental stability in lumbar arthrodesis procedures used in the treatment of degenerative disc disease, spinal stenosis, spondylolisthesis and other deformities. To maximize the rate of fusion and minimize adverse effects a controlled release formulation of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been developed that slowly releases the molecule at the intended fusion site for up to 6 weeks. PURPOSE To evaluate fusion and endplate changes for 3 BMP-2 formulations, with doses ranging from 0.15mg/mL to 0.6 mg/mL, vs an autograft control in an endplate sparing lateral interbody fusion model with time points at 1,2,3, 6, and 9 months. STUDY DESIGN/SETTING A total of 120 endplate sparing lateral interbody fusions were performed at L45 (4.5 mm x 10 mm x 20 mm PEEK cage) with bilateral posterior titanium pedicle fixation (4.5 mm x 25 mm screws, 5.5 mm rods) in 4–5-year-old ewes. Four groups were evaluated: Iliac crest autogenous cancellous bone and 3 dose levels of rhBMP2. Time points of 1,2 and 9 month (n=4 to 6 per group), 3 and 6 months (n=8 per group) were evaluated. METHODS The controlled release formulations incorporated an E. coli derived rhBMP-2 within hollow conduits of poly (DL-lactic acid-co-glycolic acid) (PLGA) using a hot melt extrusion method that retains protein activity and creates a pellet with a central lumen to maximize macroporosity. The rhBMP-2/PLGA composite is combined with a beta tricalcium phosphate granule component and delivered as a putty using a poloxamer and water carrier. Animals were carefully monitored clinically and L45 treated levels analyzed using anteroposterior and lateral Faxitron radiographs, micro computed tomography (38 microns), and nondestructive robotic range of motion (ROM) in flexion/extension, lateral bending, and axial rotation measured using a robotic 6° of freedom musculoskeletal simulator, simVITRO (Simulation Solutions and Cleveland Clinic, Ohio) nondestructively to ±7.5 Nm. Radiographic data assessed new bone formation within the cage, fusion, cage subsidence and any adverse reactions to the endplates in a blinded manner with non-parametric statistics while a 2-way ANOVA was used ROM data. Following mechanical testing samples were fixed in formalin and processed for PMMA histology. Serial sagittal sections were stained with methylene-blue/basic fuschin and sectioned using an SP1600 microtome. Histology was evaluated in a blinded manner to assess bone formation, graft resorption, endplate changes and local cell and tissue reactions. RESULTS All animals recovered uneventfully. No pedicle screw loosening was encountered, and radiographic data revealed intact endplates. Fusions were easily evaluated considering the use of PEEK cages. Autograft performed consistent within this model with progression in fusion based on radiographic and ROM mechanical testing. ROM data showed that all doses of rhBMP-2 matched the fusion strength of autograft at 6 months which was supported by radiographic evidence of new bone formation within the cage and continuous fusions. The highest dose of rhBMP-2 at 3 months matched the mechanical strength of the autograft samples at 6 months. Early timepoints of 1,2, and 3 months showed rapid onset of bone formation and subsequent remodeling for the BMP-2 formulations with low incidence and extent of osteolysis at the endplates and around the cage/endplate interface as demonstrated with PMMA histology. CONCLUSIONS A controlled release formulation of rhBMP-2 has matched the fusion performance of autograft in a challenging endplate sparing ovine model for interbody fusion. Accelerate fusion with low side-effect incidence, including an absence of endplate osteolysis was observed. FDA Device/Drug Status This abstract does not discuss or include any applicable devices or drugs. Lumber intervertebral fusion is essential for restoring segmental stability in lumbar arthrodesis procedures used in the treatment of degenerative disc disease, spinal stenosis, spondylolisthesis and other deformities. To maximize the rate of fusion and minimize adverse effects a controlled release formulation of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been developed that slowly releases the molecule at the intended fusion site for up to 6 weeks. To evaluate fusion and endplate changes for 3 BMP-2 formulations, with doses ranging from 0.15mg/mL to 0.6 mg/mL, vs an autograft control in an endplate sparing lateral interbody fusion model with time points at 1,2,3, 6, and 9 months. A total of 120 endplate sparing lateral interbody fusions were performed at L45 (4.5 mm x 10 mm x 20 mm PEEK cage) with bilateral posterior titanium pedicle fixation (4.5 mm x 25 mm screws, 5.5 mm rods) in 4–5-year-old ewes. Four groups were evaluated: Iliac crest autogenous cancellous bone and 3 dose levels of rhBMP2. Time points of 1,2 and 9 month (n=4 to 6 per group), 3 and 6 months (n=8 per group) were evaluated. The controlled release formulations incorporated an E. coli derived rhBMP-2 within hollow conduits of poly (DL-lactic acid-co-glycolic acid) (PLGA) using a hot melt extrusion method that retains protein activity and creates a pellet with a central lumen to maximize macroporosity. The rhBMP-2/PLGA composite is combined with a beta tricalcium phosphate granule component and delivered as a putty using a poloxamer and water carrier. Animals were carefully monitored clinically and L45 treated levels analyzed using anteroposterior and lateral Faxitron radiographs, micro computed tomography (38 microns), and nondestructive robotic range of motion (ROM) in flexion/extension, lateral bending, and axial rotation measured using a robotic 6° of freedom musculoskeletal simulator, simVITRO (Simulation Solutions and Cleveland Clinic, Ohio) nondestructively to ±7.5 Nm. Radiographic data assessed new bone formation within the cage, fusion, cage subsidence and any adverse reactions to the endplates in a blinded manner with non-parametric statistics while a 2-way ANOVA was used ROM data. Following mechanical testing samples were fixed in formalin and processed for PMMA histology. Serial sagittal sections were stained with methylene-blue/basic fuschin and sectioned using an SP1600 microtome. Histology was evaluated in a blinded manner to assess bone formation, graft resorption, endplate changes and local cell and tissue reactions. All animals recovered uneventfully. No pedicle screw loosening was encountered, and radiographic data revealed intact endplates. Fusions were easily evaluated considering the use of PEEK cages. Autograft performed consistent within this model with progression in fusion based on radiographic and ROM mechanical testing. ROM data showed that all doses of rhBMP-2 matched the fusion strength of autograft at 6 months which was supported by radiographic evidence of new bone formation within the cage and continuous fusions. The highest dose of rhBMP-2 at 3 months matched the mechanical strength of the autograft samples at 6 months. Early timepoints of 1,2, and 3 months showed rapid onset of bone formation and subsequent remodeling for the BMP-2 formulations with low incidence and extent of osteolysis at the endplates and around the cage/endplate interface as demonstrated with PMMA histology. A controlled release formulation of rhBMP-2 has matched the fusion performance of autograft in a challenging endplate sparing ovine model for interbody fusion. Accelerate fusion with low side-effect incidence, including an absence of endplate osteolysis was observed.