Healos/rhGDF-5** Induces Fusion in a Rabbit Posterolateral Lumbar Fusion Model

Summary: Recombinant human growth and differentiation factor-5 (rhGDF-5) has been introduced as a potential bone graft alternative with Healos as a carrier. This was tested in a rabbit posterolateral lumbar fusion model. A fusion rate of 100% was seen for each of three rhGDF-5 doses, with autograft leading to a fusion rate of 38% and Healos alone leading to a fusion rate of 0%. Histology and radiographic imaging was also performed.

Introduction: Much work is being done to define potential bone graft alternatives to alleviate the need for autograft with fusion procedures. Recombinant human growth and differentiation factor-5 (rhGDF-5) is one such osteoinductive molecule which is under consideration. This has been evaluated in some preclinical animal studies and is now being investigated in humans.

Methods: The commonly used New Zealand white rabbit posterolateral lumbar fusion model was used to evaluate five fusion constructs (n=13 for each group): autograft, Healos alone (cross-linked type I collagen with a hydroxyapatite coating), and three doses of rhGDF-5 lyophilized to the Healos carrier. The doses studied were 0.5mg/cc, 1.0mg/cc, and 1.5mg/cc, with one 1.5cc strip used per side for each procedure. At eight weeks, the rabbits were sacrificed and evaluated by manual palpation, radiographs, and histology.

Results: Two animals (3%) were lost to peri-operative complications. Fusion results by manual palpation were: autograft 38% (5/13), Healos alone 0% (0/13), and all doses of Healos/rhGDF-5 100% (13/13 for each). Radiographs had a sensitivity of 84% and specificity of 86%. Histology demonstrated abundant bone formation with numerous osteoblasts and trabecular architecture in most rhGDF-5-induced fusion masses. The exception was in the high dose group where some fusion masses were found to have an outer shell of bone surrounding non-bony tissue.

Discussion: Using a well-established lumbar fusion model, Healos/rhGDF-5 induced fusion in 100% of the animals studied. Solid bone formation in the lower two doses evaluated suggested appropriate dosing. The bone shells seen in the highest dose group suggested that this dose was too high for the application being evaluated. Overall, the results of this study were encouraging and support further ongoing studies.

FDA Diclosure Cleared: No ** rhGDF-5