Introduction
Lumber intervertebral fusion is essential for restoring segmental stability in lumbar arthrodesis procedures. To maximise the fusion rate and minimise adverse effects a controlled-release formulation of recombinant human bone morphogenetic protein-2(rhBMP-2) has been developed that reduces drug burst and extends the release over time.
Method
120 endplate-sparing lateral interbody fusions were performed at L4-5 using a plain PEEK cage with bilateral posterior titanium pedicle fixation in 4–5-year-old ewes. Four groups were evaluated: Iliac crest autogenous cancellous bone and 3 dose levels of rhBMP2 ranging from 0.15 to 0.6 mg/mL. Time points of 1, 2, 3, 6 and 9 months were evaluated. The controlled release formulations incorporated an E.coli derived rhBMP-2 encapsulated within poly(DL-lactic acid-co-glycolic acid) (PLGA), combined with a beta-tricalcium phosphate granule component and delivered as a putty using a poloxamer and water carrier. PMMA histology was evaluated in a blinded manner to assess bone formation, graft resorption, endplate changes and local cell and tissue reactions. Fusion outcomes were assessed in a blinded manner using micro-computed tomography, manual palpation, and robotic range of motion (ROM) testing.
Results
All animals recovered uneventfully. No pedicle screw loosening was encountered, and radiographic data revealed intact endplates. All groups showed clear progression in fusion based on radiographic and ROM testing. All doses of rhBMP-2 matched the fusion range of motion properties of autograft at 6 months. Early time points showed rapid onset of bone formation and subsequent remodelling for the BMP-2 formulations. As demonstrated with PMMA histology, there was no evidence of product-related osteolysis at the endplates.
Conclusion
A controlled release formulation of rhBMP-2 has matched the fusion performance of autograft in a challenging endplate-sparing ovine model for interbody fusion. Accelerated fusion with low side-effect incidence, including an absence of endplate osteolysis, was observed.