Reliable and rapid bone formation is the goal of biologics and cell-based spinal fusion technologies. While no cell-based therapy alone has been successful, recombinant human bone morphogenetic protein-2 (rhBMP-2) has been successfully used in a wide spectrum of patients undergoing a variety of spinal fusion procedures since its approval by the United States Food and Drug Administration (FDA) in 2002. However, the question remains how to improve the biologic efficiency, or osteoinductivity, of rhBMP-2 for successful application in the most challenging patients undergoing spinal fusion or to reduce the doses currently required. The present study investigated how varying the cellular environments through the addition of freshly harvested bone marrow aspirate (BMA) modulates rhBMP-2 efficiency.Methods:
An L4-L5 posterolateral intertransverse process spinal fusion procedure was performed in Lewis rats. The implants were a subeffective concentration of 0.006 mg/mL of rhBMP-2/two absorbable collagen sponges (ACS) plus directly applied fresh syngeneic BMA transplants (n = 18), 0.006-mg/mL rhBMP-2/two ACS/side (n = 12), 0.006-mg/mL rhBMP-2/one ACS/side (n = 12), or BMA/one ACS/side (n = 6). Rats were killed at eight weeks and were evaluated with use of manual palpation, radiographs, and biomechanical testing.Results:
BMA plus 0.006-mg/mL rhBMP-2/ACS significantly increased the L4-L5 fusion rate to 89% (sixteen of eighteen) compared with a base fusion rate of 33% (four of twelve) to 50% (six of twelve) for rats implanted with rhBMP-2/ACS (p < 0.05), with no difference in strength or stiffness between conditions. No fusion or bone formation was observed in the six rats that received BMA/ACS alone.Conclusions:
Less rhBMP-2 was needed for effect when mixed with BMA. A nearly twofold increase in the fusion rate was found when BMA was mixed with a deliberate subeffective concentration of rhBMP-2. There was no improvement in terms of fusion strength or stiffness.Clinical Relevance:
Adjuvants such as BMA with rhBMP-2 may improve fusion success, allow marked dose reduction per segment in multilevel spinal surgery, result in cost savings, and/or decrease dose-related complications. This warrants further study prior to clinical implementation.