Ceramic granules enhanced with B2A peptide for lumbar interbody spine fusion: an experimental study using an instrumented model in sheep.

OBJECT New generations of devices for spinal interbody fusion are expected to arise from the combined use of bioactive peptides and porous implants. The purpose of this dose-ranging study was to evaluate the fusion characteristics of porous ceramic granules (CGs) coated with the bioactive peptide B2A2-K-NS (B2A) by using a model of instrumented lumbar interbody spinal fusion in sheep. METHODS Instrumented spinal arthrodesis was performed in 40 operative sites in 20 adult sheep. In each animal, posterior instrumentation (pedicle screw and rod) and a polyetheretherketone cage were placed in 2 single-level procedures (L2-3 and L4-5). All cages were packed with graft material prior to implantation. The graft materials were prepared by mixing (1:1 vol/vol) CGs with or without a B2A coating and morselized autograft. Ceramic granules were coated with B2A at 50, 100, 300, and 600 microg/ml granules (50-B2A/CG, 100-B2A/CG, 300-B2A/CG, and 600-B2A/CG, respectively), resulting in 4 B2A-coated groups plus a control group (uncoated CGs). Graft material from each of these groups was implanted in 8 operative sites. Four months after arthrodesis, interbody fusion status was assessed with CT, and the interbody site was further evaluated with quantitative histomorphometry. RESULTS All B2A/CG groups had higher CT-confirmed interbody fusion rates compared with those in controls (CGs only). Seven of 8 sites were fused in the 50-B2A/CG, 100-B2A/CG, and 300-B2A/CG groups, whereas 5 of 8 sites were fused in the group that had received uncoated CGs. New woven and lamellar bone spanned the fusion sites with excellent osseointegration. There was no heterotopic ossification or other untoward events attributed to the use of B2A/CG in any group. Each B2A/CG treatment produced more new bone than that in the CG group. CONCLUSIONS Bioactive treatment with B2A effectively enhanced the fusion capacity of porous CGs. These findings suggest that B2A/CG may well represent a new generation of biomaterials for lumbar interbody fusion and indicate that additional studies are warranted.

[1]  S. Jatana,et al.  Neurologic impairment from ectopic bone in the lumbar canal: a potential complication of off-label PLIF/TLIF use of bone morphogenetic protein-2 (BMP-2). , 2008, The spine journal : official journal of the North American Spine Society.

[2]  Joseph D. Smucker,et al.  B2A Peptide on Ceramic Granules Enhance Posterolateral Spinal Fusion in Rabbits Compared With Autograft , 2008, Spine.

[3]  G. Buttermann.  Prospective nonrandomized comparison of an allograft with bone morphogenic protein versus an iliac-crest autograft in anterior cervical discectomy and fusion. , 2008, The spine journal : official journal of the North American Spine Society.

[4]  Michael A Mont,et al.  Evidence supporting the use of bone morphogenetic proteins for spinal fusion surgery , 2008, Expert review of medical devices.

[5]  Y. R. Rampersaud,et al.  Heterotopic Bone Formation With the Use of rhBMP2 in Posterior Minimal Access Interbody Fusion: A CT Analysis , 2007, Spine.

[6]  Sean A F Peel,et al.  An Evaluation of Hydroxyapatite and Biphasic Calcium Phosphate in Combination With Pluronic F127 and BMP on Bone Repair , 2007, The Journal of craniofacial surgery.

[7]  I Harvey,et al.  Clinical effectiveness and cost-effectiveness of bone morphogenetic proteins in the non-healing of fractures and spinal fusion: a systematic review. , 2007, Health technology assessment.

[8]  D. Anderson,et al.  Minimally invasive techniques for lumbar interbody fusions. , 2007, The Orthopedic clinics of North America.

[9]  B. Cunningham,et al.  A Comparative Biomechanical Analysis of Spinal Instability and Instrumentation of the Cervicothoracic Junction: An In Vitro Human Cadaveric Model , 2007, Journal of spinal disorders & techniques.

[10]  D. Carnes,et al.  Augmentation of osseous phenotypes in vivo with a synthetic peptide , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[11]  Yi Liu,et al.  A synthetic, bioactive PDGF mimetic with binding to both α-PDGF and β-PDGF receptors , 2007 .

[12]  N. P. Haas,et al.  Quantitative assessment of growth factors in reaming aspirate, iliac crest, and platelet preparation. , 2006, Bone.

[13]  S. Ikeda,et al.  Possible involvement of bone morphogenetic protein 2 in heterotopic ossification in metastatic lesion from urothelial carcinoma of bladder , 2006, International journal of urology : official journal of the Japanese Urological Association.

[14]  C. V. van Blitterswijk,et al.  Cross-species comparison of ectopic bone formation in biphasic calcium phosphate (BCP) and hydroxyapatite (HA) scaffolds. , 2006, Tissue engineering.

[15]  C. V. van Blitterswijk,et al.  A comparison of bone formation in biphasic calcium phosphate (BCP) and hydroxyapatite (HA) implanted in muscle and bone of dogs at different time periods. , 2006, Journal of biomedical materials research. Part A.

[16]  Clemens A van Blitterswijk,et al.  Osteoinduction by biomaterials--physicochemical and structural influences. , 2006, Journal of biomedical materials research. Part A.

[17]  K. Takahashi,et al.  Synthetic peptide F2A4-K-NS mimics fibroblast growth factor-2 in vitro and is angiogenic in vivo. , 2006, International journal of molecular medicine.

[18]  B. Rahn,et al.  Osteopromotion by a &bgr;-Tricalcium Phosphate/Bone Marrow Hybrid Implant for Use in Spine Surgery , 2006, Spine.

[19]  B. Kwon,et al.  Carrier materials for spinal fusion. , 2005, The spine journal : official journal of the North American Spine Society.

[20]  Jeffrey C. Wang,et al.  Demineralized bone matrix and spinal arthrodesis. , 2005, The spine journal : official journal of the North American Spine Society.

[21]  A. Minami,et al.  An Investigational Study on the Healing Process of Anterior Spinal Arthrodesis Using a Bioactive Ceramic Spacer and the Change in Load-Sharing of Spinal Instrumentation , 2005, Spine.

[22]  R. Welch,et al.  Recombinant Human Bone Morphogenic Protein-2-Enhanced Anterior Spine Fusion Without Bone Encroachment Into the Spinal Canal: A Histomorphometric Study in a Thoracoscopically Instrumented Porcine Model , 2005, Spine.

[23]  Safdar N. Khan,et al.  Use of Osteopromotive Growth Factors, Demineralized Bone Matrix, and Ceramics to Enhance Spinal Fusion , 2005, The Journal of the American Academy of Orthopaedic Surgeons.

[24]  Daniel H. Kim,et al.  Evaluation of HealosMP52 Osteoinductive Bone Graft for Instrumented Lumbar Intertransverse Process Fusion in Sheep , 2004, Spine.

[25]  L. Peña,et al.  Multidomain Synthetic Peptide B2A2 Synergistically Enhances BMP‐2 In Vitro , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[26]  Daniel H. Kim,et al.  Open versus endoscopic lumbar pedicle screw fixation and posterolateral fusion in a sheep model: a feasibility study. , 2004, The spine journal : official journal of the North American Spine Society.

[27]  Safdar N. Khan,et al.  The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in orthopaedic applications , 2004, Expert opinion on biological therapy.

[28]  A. Minamide,et al.  Experimental study of carriers of bone morphogenetic protein used for spinal fusion , 2004, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[29]  C. Fisher,et al.  Effects of Endplate Removal on the Structural Properties of the Lower Lumbar Vertebral Bodies , 2003, Spine.

[30]  A. Weckbach,et al.  Evaluation of an injectable calcium phosphate cement as an autograft substitute for transpedicular lumbar interbody fusion: a controlled, prospective study in the sheep model , 2003, European Spine Journal.

[31]  S. Boden,et al.  Overview of the Biology of Lumbar Spine Fusion and Principles for Selecting a Bone Graft Substitute , 2002, Spine.

[32]  M. Foster,et al.  Characterization of a developing lumbar arthrodesis in a sheep model with quantitative instability. , 2002, The spine journal : official journal of the North American Spine Society.

[33]  Thomas R. Oxland,et al.  Mapping the Structural Properties of the Lumbosacral Vertebral Endplates , 2001, Spine.

[34]  K. Kaneda,et al.  The Effects of Rigid Spinal Instrumentation and Solid Bony Fusion on Spinal Kinematics: A Posterolateral Spinal Arthrodesis Model , 1998, Spine.

[35]  K. Kaneda,et al.  Maturation of the Posterolateral Spinal Fusion and Its Effect on Load-Sharing of Spinal Instrumentation. An In Vivo Sheep Model* , 1997, The Journal of bone and joint surgery. American volume.

[36]  L. Claes,et al.  Are Sheep Spines a Valid Biomechanical Model for Human Spines? , 1997, Spine.

[37]  L. Claes,et al.  Anatomy of the sheep spine and its comparison to the human spine , 1997, The Anatomical record.

[38]  N. Epstein.  Efficacy of different bone volume expanders for augmenting lumbar fusions. , 2008, Surgical neurology.

[39]  C. W. Adams,et al.  Macrophage histology in paraffin-embedded multiple sclerosis plaques is demonstrated by the monoclonal pan-macrophage marker HAM-56: correlation with chronicity of the lesion , 2004, Acta Neuropathologica.

[40]  J. Bouler,et al.  Macroporous calcium phosphate ceramic: a prospective study of 106 cases in lumbar spinal fusion. , 1999, Journal of long-term effects of medical implants.