title: Effects of a perfusion bioreactor activated novel bone substitute in spine fusion in sheep.
abstract: OBJECTIVE
  To evaluate the effect of a large perfusion-bioreactor cell-activated bone substitute, on a two-level large posterolateral spine fusion sheep model.
  
  
  METHODS
  A 50 mm long porous biphasic-calcium-phosphate bone substitute reinforced with poly(D,L-lactide) and, activated with bone marrow derived mononuclear-cells (BMNC) was used. Eighteen sheep were divided into two groups and one group (n = 9) had BMNC-activated bone substitutes and cell-free substitutes implanted. The second group (n = 9) had autograft supplemented with BMNC and regular autograft implanted. The implant material was alternated between spine level L2-L3 and L4-L5 in both groups. MicroCT was used to compare the spine fusion efficacy and bone structure of the two groups as well as the implanted bone substitutes and non-implanted substitutes.
  
  
  RESULTS
  After 4½ months six sheep survived in both groups and we found five spine levels were fused when using activated bone substitute compared to three levels with cell-free bone substitute (p = 0.25). Five sheep fused at both levels in the autograft group. A significant increased bone density (p < 0.05) and anisotropy (p < 0.05) was found in the group of activated bone substitutes compared to cell-free bone substitute and no difference existed on the other parameters. The implanted bone substitutes had a significant higher bone density and trabecular thickness than non-implanted bone substitutes, thus indicating that the PLA reinforced BCP had osteoconductive properties (p < 0.05). No effect of the supplemented BMNC to autograft was observed. The autograft group had a significant higher bone density, trabecular thickness and degree of anisotropy than the implanted bone substitutes (p < 0.05), but a lower connectivity density existed (p < 0.05). This indicates that though the activated substitute might have a similar fusion efficacy to autograft, the fusion bridge is not of equal substance.
  
  
  CONCLUSIONS
  We found that bioreactor-generated cell-based bone substitutes seemed superior in fusion ability when compared to cell-free bone substitute and comparable to autograft in fusion ability, but not in bone structure. This combined with the favorable biocompatible abilities and strength comparable to human cancellous bone indicates that it might be a suitable bone substitute in spine fusion procedures.
authors: Department of Orthopaedics and Traumatology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, J. B. Winsløwsvej 15 st.th., 5000, Odense C, Denmark. j.roed.sorensen@gmail.com
authors: Jesper Roed
authors: JR
authors: Sørensen
authors: Kariatta Ester
authors: KE
authors: Koroma
authors: Ming
authors: M
authors: Ding
authors: David
authors: D
authors: Wendt
authors: Stig
authors: S
authors: Jespersen
authors: Maria Vinther
authors: MV
authors: Juhl
authors: Naseem
authors: N
authors: Theilgaard
authors: Ivan
authors: I
authors: Martin
authors: Søren
authors: S
authors: Overgaard
mesh_terms: D000818:Animals; D019149:Bioreactors; D001854:Bone Marrow Cells; D018786:Bone Substitutes / Q000737:chemistry / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000627:therapeutic use; D017886:Durapatite / Q000627:therapeutic use; D005260:Female; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging* / Q000601:surgery; D011091:Polyesters / Q000627:therapeutic use; D012756:Sheep; D013123:Spinal Fusion / Q000379:methods*; D014057:Tomography, X-Ray Computed
chemical_list: D018786:Bone Substitutes; D002130:Calcium Phosphates; D011091:Polyesters; C485817:beta-tricalcium phosphate; C499699:hydroxyapatite-polylactide; D017886:Durapatite