Radiographic, Histologic and Mechanical Comparison of NanoFUSE® DBM and a Bioactive Glass in a Rabbit Spinal Fusion Model
International Journal of Biomedical Materials Research
Volume 3, Issue 3, June 2015, Pages: 19-33
Received: Jul. 2, 2015; Accepted: Jul. 21, 2015; Published: Jul. 31, 2015
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James F. Kirk, Research and Development Department, Nanotherapeutics, Inc., Alachua, FL
Gregg Ritter, Research and Development Department, Nanotherapeutics, Inc., Alachua, FL
Michael J. Larson, Ibex Preclinical Research, Inc., Logan, UT
Robert C. Waters, Research and Development Department, Nanotherapeutics, Inc., Alachua, FL
Isaac finger, Research and Development Department, Nanotherapeutics, Inc., Alachua, FL
John Waters, Research and Development Department, Nanotherapeutics, Inc., Alachua, FL
John H. Abernethy, Research and Development Department, Nanotherapeutics, Inc., Alachua, FL
Dhyana Sankar, Research and Development Department, Nanotherapeutics, Inc., Alachua, FL
James D. Talton, Research and Development Department, Nanotherapeutics, Inc., Alachua, FL
Ronald R. Cobb, Research and Development Department, Nanotherapeutics, Inc., Alachua, FL
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Autologous bone has long been the gold standard for bone void fillers. However, the limited supply and morbidity associated with using autologous graft material has led to the development of many different bone graft substitutes. The use of bone graft extenders has become an essential component in a number of orthopedic applications including spinal fusion. This study compares the ability of NanoFUSE® DBM and a bioactive glass product (NovaBone Putty®) to induce spinal fusion in a rabbit model. NanoFUSE® DBM is a combination of allogeneic human bone and bioactive glass. NanoFUSE® DBM alone, and in combination with autograft, and NovaBone Putty®, were implanted in the posterior lateral intertransverse process region of the rabbit spine. The spines were evaluated for fusion at 4, 8, 12, and 24 weeks for fusion of the L4-L5 transverse processes using a total of 64 skeletally mature rabbits. Samples were evaluated by manual palpation, radiographically, histologically, and by mechanical testing. Radiographical, histological, and palpation measurements demonstrated the ability of NanoFUSE® DBM to induce new bone formation. The material in combination with autograft performed as well as autograft alone with respect to new bone formation and bridging bone at all time points with the exception of four week radiographic analyses. In addition, the combination of allogeneic human bone and bioactive glass found in NanoFUSE® DBM was observed to be superior to the bioactive glass product NovaBone Putty® in this rabbit model of spinal fusion. This in vivo study demonstrates the DBM and bioactive glass combination, NanoFUSE® DBM, could be an effective bone graft extender in posterolateral spinal fusions.
Demineralized Bone Matrix, Bioactive Glass, Spinal Fusion, Radiography, Histology
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James F. Kirk, Gregg Ritter, Michael J. Larson, Robert C. Waters, Isaac finger, John Waters, John H. Abernethy, Dhyana Sankar, James D. Talton, Ronald R. Cobb, Radiographic, Histologic and Mechanical Comparison of NanoFUSE® DBM and a Bioactive Glass in a Rabbit Spinal Fusion Model, International Journal of Biomedical Materials Research. Vol. 3, No. 3, 2015, pp. 19-33. doi: 10.11648/j.ijbmr.20150303.11
Goulet, J.A., et al., Autogenous iliac crest bone graft. Complications and functional assessment. Clin Orthop Relat Res, 1997(339): p. 76-81.
Heary, R.F., et al., Persistent iliac crest donor site pain: independent outcome assessment. Neurosurgery, 2002. 50(3): p. 510-6; discussion 516-7.
Ubhi, C.S. and D.L. Morris, Fracture and herniation of bowel at bone graft donor site in the iliac crest. Injury, 1984. 16(3): p. 202-3.
Younger, E.M. and M.W. Chapman, Morbidity at bone graft donor sites. J Orthop Trauma, 1989. 3(3): p. 192-5.
Biswas, D., et al., Augmented demineralized bone matrix: a potential alternative for posterolateral lumbar spinal fusion. Am J Orthop (Belle Mead NJ), 2010. 39(11): p. 531-538.
Martin, G.J., Jr., et al., New formulations of demineralized bone matrix as a more effective graft alternative in experimental posterolateral lumbar spine arthrodesis. Spine (Phila Pa 1976), 1999. 24(7): p. 637-45.
Sassard, W.R., et al., Augmenting local bone with Grafton demineralized bone matrix for posterolateral lumbar spine fusion: avoiding second site autologous bone harvest. Orthopedics, 2000. 23(10): p. 1059-64; discussion 1064-5.
Rosenthal, R.K., J. Folkman, and J. Glowacki, Demineralized bone implants for nonunion fractures, bone cysts, and fibrous lesions. Clin Orthop Relat Res, 1999(364): p. 61-9.
Dodds, R.A., et al., Biomechanical and radiographic comparison of demineralized bone matrix, and a coralline hydroxyapatite in a rabbit spinal fusion model. J Biomater Appl, 2010. 25(3): p. 195-215.
Moore, S.T., et al., Osteoconductivity and Osteoinductivity of Puros(R) DBM Putty. J Biomater Appl, 2010.
Hattar, S., et al., Behaviour of moderately differentiated osteoblast-like cells cultured in contact with bioactive glasses. Eur Cell Mater, 2002. 4: p. 61-9.
Kokubo, T., et al., Ca,P-rich layer formed on high-strength bioactive glass-ceramic A-W. J Biomed Mater Res, 1990. 24(3): p. 331-43.
Hak, D.J., The use of osteoconductive bone graft substitutes in orthopaedic trauma. J Am Acad Orthop Surg, 2007. 15(9): p. 525-36.
Moore, W.R., S.E. Graves, and G.I. Bain, Synthetic bone graft substitutes. ANZ J Surg, 2001. 71(6): p. 354-61.
Fujishiro, Y., L.L. Hench, and H. Oonishi, Quantitative rates of in vivo bone generation for Bioglass and hydroxyapatite particles as bone graft substitute. J Mater Sci Mater Med, 1997. 8(11): p. 649-52.
Oonishi, H., et al., Particulate bioglass compared with hydroxyapatite as a bone graft substitute. Clin Orthop Relat Res, 1997(334): p. 316-25.
Wheeler, D.L., et al., Assessment of resorbable bioactive material for grafting of critical-size cancellous defects. J Orthop Res, 2000. 18(1): p. 140-8.
Wheeler, D.L., et al., Effect of bioactive glass particle size on osseous regeneration of cancellous defects. J Biomed Mater Res, 1998. 41(4): p. 527-33.
Glowacki, J., et al., Application of the biological principle of induced osteogenesis for craniofacial defects. Lancet, 1981. 1(8227): p. 959-62.
Mulliken, J.B., et al., Use of demineralized allogeneic bone implants for the correction of maxillocraniofacial deformities. Ann Surg, 1981. 194(3): p. 366-72.
Tiedeman, J.J., et al., The role of a composite, demineralized bone matrix and bone marrow in the treatment of osseous defects. Orthopedics, 1995. 18(12): p. 1153-8.
Mulliken, J.B., L.B. Kaban, and J. Glowacki, Induced osteogenesis--the biological principle and clinical applications. J Surg Res, 1984. 37(6): p. 487-96.
Urist, M.R., R.J. DeLange, and G.A. Finerman, Bone cell differentiation and growth factors. Science, 1983. 220(4598): p. 680-6.
Urist, M.R. and T.A. Dowell, Inductive substratum for osteogenesis in pellets of particulate bone matrix. Clin Orthop Relat Res, 1968. 61: p. 61-78.
Urist, M.R. and B.S. Strates, Bone formation in implants of partially and wholly demineralized bone matrix. Including observations on acetone-fixed intra and extracellular proteins. Clin Orthop Relat Res, 1970. 71: p. 271-8.
Morone, M.A. and S.D. Boden, Experimental posterolateral lumbar spinal fusion with a demineralized bone matrix gel. Spine (Phila Pa 1976), 1998. 23(2): p. 159-67.
Edwards, J.T., M.H. Diegmann, and N.L. Scarborough, Osteoinduction of human demineralized bone: characterization in a rat model. Clin Orthop Relat Res, 1998(357): p. 219-28.
Grauer, J.N., et al., Posterolateral lumbar fusions in athymic rats: characterization of a model. Spine J, 2004. 4(3): p. 281-6.
Lee, J.H., et al., Biomechanical and histomorphometric study on the bone-screw interface of bioactive ceramic-coated titanium screws. Biomaterials, 2005. 26(16): p. 3249-57.
Peterson, B., et al., Osteoinductivity of commercially available demineralized bone matrix. Preparations in a spine fusion model. J Bone Joint Surg Am, 2004. 86-A(10): p. 2243-50.
Adkisson, H.D., et al., Rapid quantitative bioassay of osteoinduction. J Orthop Res, 2000. 18(3): p. 503-11.
Desikan, R.S., et al., Automated MRI measures predict progression to Alzheimer's disease. Neurobiol Aging, 2010. 31(8): p. 1364-74.
Glowacki, J., A review of osteoinductive testing methods and sterilization processes for demineralized bone. Cell Tissue Bank, 2005. 6(1): p. 3-12.
Han, B., B. Tang, and M.E. Nimni, Quantitative and sensitive in vitro assay for osteoinductive activity of demineralized bone matrix. J Orthop Res, 2003. 21(4): p. 648-54.
Lomas, R.J., et al., An evaluation of the capacity of differently prepared demineralised bone matrices (DBM) and toxic residuals of ethylene oxide (EtOx) to provoke an inflammatory response in vitro. Biomaterials, 2001. 22(9): p. 913-21.
Gerhardt, L.C., et al., Neocellularization and neovascularization of nanosized bioactive glass-coated decellularized trabecular bone scaffolds. J Biomed Mater Res A, 2013. 101(3): p. 827-41.
Leu, A. and J.K. Leach, Proangiogenic potential of a collagen/bioactive glass substrate. Pharm Res, 2008. 25(5): p. 1222-9.
Milkovic, L., et al., Effects of Cu-doped 45S5 bioactive glass on the lipid peroxidation-associated growth of human osteoblast-like cells in vitro. J Biomed Mater Res A, 2014. 102(10): p. 3556-61.
Wu, C., et al., Stimulation of osteogenic and angiogenic ability of cells on polymers by pulsed laser deposition of uniform akermanite-glass nanolayer. Acta Biomater, 2014. 10(7): p. 3295-306.
Kirk, J.F., et al., Osteoconductivity and osteoinductivity of NanoFUSE((R)) DBM. Cell Tissue Bank, 2013. 14(1): p. 33-44.
Boden, S.D., J.H. Schimandle, and W.C. Hutton, An experimental lumbar intertransverse process spinal fusion model. Radiographic, histologic, and biomechanical healing characteristics. Spine (Phila Pa 1976), 1995. 20(4): p. 412-20.
Bauer, T.W., Bone graft substitutes. Skeletal Radiol, 2007. 36(12): p. 1105-7.
Bauer, T.W. and G.F. Muschler, Bone graft materials. An overview of the basic science. Clin Orthop Relat Res, 2000(371): p. 10-27.
Berven, S., et al., Clinical applications of bone graft substitutes in spine surgery: consideration of mineralized and demineralized preparations and growth factor supplementation. Eur Spine J, 2001. 10 Suppl 2: p. S169-77.
Xynos, I.D., et al., Bioglass 45S5 stimulates osteoblast turnover and enhances bone formation In vitro: implications and applications for bone tissue engineering. Calcif Tissue Int, 2000. 67(4): p. 321-9.
Wilson, J., et al., Toxicology and biocompatibility of bioglasses. J Biomed Mater Res, 1981. 15(6): p. 805-17.
Xynos, I.D., et al., Ionic products of bioactive glass dissolution increase proliferation of human osteoblasts and induce insulin-like growth factor II mRNA expression and protein synthesis. Biochem Biophys Res Commun, 2000. 276(2): p. 461-5.
Xynos, I.D., et al., Gene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass 45S5 dissolution. J Biomed Mater Res, 2001. 55(2): p. 151-7.
Hing, K.A., L.F. Wilson, and T. Buckland, Comparative performance of three ceramic bone graft substitutes. Spine J, 2007. 7(4): p. 475-90.
Wilson, J. and S.B. Low, Bioactive ceramics for periodontal treatment: comparative studies in the Patus monkey. J Appl Biomater, 1992. 3(2): p. 123-9.
Moreira-Gonzalez, A., et al., Evaluation of 45S5 bioactive glass combined as a bone substitute in the reconstruction of critical size calvarial defects in rabbits. J Craniofac Surg, 2005. 16(1): p. 63-70.
Vogel, M., et al., In vivo comparison of bioactive glass particles in rabbits. Biomaterials, 2001. 22(4): p. 357-62.
Bozic, K.J., et al., In vivo evaluation of coralline hydroxyapatite and direct current electrical stimulation in lumbar spinal fusion. Spine (Phila Pa 1976), 1999. 24(20): p. 2127-33.
Lehman, R.A., Jr., et al., The effect of alendronate sodium on spinal fusion: a rabbit model. Spine J, 2004. 4(1): p. 36-43.
Liao, S.S., et al., Lumbar spinal fusion with a mineralized collagen matrix and rhBMP-2 in a rabbit model. Spine (Phila Pa 1976), 2003. 28(17): p. 1954-60.
Long, J., et al., The effect of cyclooxygenase-2 inhibitors on spinal fusion. J Bone Joint Surg Am, 2002. 84-A(10): p. 1763-8.
Tay, B.K., et al., Use of a collagen-hydroxyapatite matrix in spinal fusion. A rabbit model. Spine (Phila Pa 1976), 1998. 23(21): p. 2276-81.
Sandhu, H.S. and S.N. Khan, Animal models for preclinical assessment of bone morphogenetic proteins in the spine. Spine (Phila Pa 1976), 2002. 27(16 Suppl 1): p. S32-8.
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