title: Bone marrow enhances the performance of rhBMP-2 in spinal fusion: a rodent model.
abstract: BACKGROUND
  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.
authors: Tissue Engineering Laboratory, Spine Center, Department of Surgery, Cedars-Sinai Medical Center, 444 South San Vicente Boulevard, Suite 901, Los Angeles, CA 90048, USA.
authors: Hyun W
authors: HW
authors: Bae
authors: Li
authors: L
authors: Zhao
authors: Linda E A
authors: LE
authors: Kanim
authors: Pamela
authors: P
authors: Wong
authors: Deborah
authors: D
authors: Marshall
authors: Rick B
authors: RB
authors: Delamarter
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D016026:Bone Marrow Transplantation; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002452:Cell Count; D003094:Collagen / Q000494:pharmacology; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects / Q000601:surgery*; D010173:Palpation; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D013123:Spinal Fusion / Q000379:methods*; D015503:Surgical Sponges; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen