Abstract
Bone graft substitutes have become an essential component in a number of orthopedic applications. 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. Allogeneic demineralized bone matrix (DBM) has been used extensively to supplement autograft bone because of its inherent osteoconductive and osteoinductive properties. Synthetic and natural bone graft substitutes that do not contain growth factors are considered to be osteoconductive only. Bioactive glass has been shown to facilitate graft containment at the operative site as well as activate cellular osteogenesis. In the present study, we present the results of a comprehensive in vitro and in vivo characterization of a combination of allogeneic human bone and bioactive glass bone void filler, NanoFUSE® DBM. NanoFUSE® DBM is shown to be biocompatible in a number of different assays and has been cleared by the FDA for use in bone filling indications. Data are presented showing the ability of the material to support cell attachment and proliferation on the material thereby demonstrating the osteoconductive nature of the material. NanoFUSE® DBM was also shown to be osteoinductive in the mouse thigh muscle model. These data demonstrate that the DBM and bioactive glass combination, NanoFUSE® DBM, could be an effective bone graft substitute.
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Refereneces
Berven S, Tay BK, Kleinstueck FS, Bradford DS (2001) Clinical applications of bone graft substitutes in spine surgery: consideration of mineralized and demineralized preparations and growth factor supplementation. Eur Spine J 10(Suppl 2):S169–S177. doi:10.1007/s005860100270
Biswas D, Bible JE, Whang PG, Miller CP, Jaw R, Miller S, Grauer JN (2010) Augmented demineralized bone matrix: a potential alternative for posterolateral lumbar spinal fusion. Am J Orthop 39(11):531–538
Cornell CN (1999) Osteoconductive materials and their role as substitutes for autogenous bone grafts. Orthop Clin North Am 30(4):591–598
Edwards JT, Diegmann MH, Scarborough NL (1998) Osteoinduction of human demineralized bone: characterization in a rat model. Clin Orthop Relat Res 357:219–228
Fujishiro Y, Hench LL, Oonishi H (1997) Quantitative rates of in vivo bone generation for Bioglass and hydroxyapatite particles as bone graft substitute. J Mater Sci Mater Med 8(11):649–652
Glowacki J, Kaban LB, Murray JE, Folkman J, Mulliken JB (1981) Application of the biological principle of induced osteogenesis for craniofacial defects. Lancet 1(8227):959–962
Goulet JA, Senunas LE, DeSilva GL, Greenfield ML (1997) Autogenous iliac crest bone graft. Complications and functional assessment. Clin Orthop Relat Res 339:76–81
Hattar S, Berdal A, Asselin A, Loty S, Greenspan DC, Sautier JM (2002) Behaviour of moderately differentiated osteoblast-like cells cultured in contact with bioactive glasses. Eur Cells Mater 4:61–69
Heary RF, Schlenk RP, Sacchieri TA, Barone D, Brotea C (2002) Persistent iliac crest donor site pain: independent outcome assessment. Neurosurgery 50(3):510–516 discussion 516–517
Hench LL, Paschall HA (1973) Direct chemical bond of bioactive glass-ceramic materials to bone and muscle. J Biomed Mater Res 7(3):25–42. doi:10.1002/jbm.820070304
Hench LL, Xynos ID, Polak JM (2004) Bioactive glasses for in situ tissue regeneration. J Biomater Sci Polym Ed 15(4):543–562
Hoylaerts MF, Ding L, Narisawa S, Van Kerckhoven S, Millan JL (2006) Mammalian alkaline phosphatase catalysis requires active site structure stabilization via the N-terminal amino acid microenvironment. Biochemistry 45(32):9756–9766. doi:10.1021/bi052471+
Ito G, Matsuda T, Inoue N, Kamegai T (1987) A histological comparison of the tissue interface of bioglass and silica glass. J Biomed Mater Res 21(4):485–497. doi:10.1002/jbm.820210408
Kasten P, Luginbuhl R, van Griensven M, Barkhausen T, Krettek C, Bohner M, Bosch U (2003) Comparison of human bone marrow stromal cells seeded on calcium-deficient hydroxyapatite, beta-tricalcium phosphate and demineralized bone matrix. Biomaterials 24(15):2593–2603
Kitsugi T, Nakamura T, Yamamura T, Kokubu T, Shibuya T, Takagi M (1987) SEM-EPMA observation of three types of apatite-containing glass-ceramics implanted in bone: the variance of a Ca-P-rich layer. J Biomed Mater Res 21(10):1255–1271. doi:10.1002/jbm.820211008
Kokubo T, Ito S, Huang ZT, Hayashi T, Sakka S, Kitsugi T, Yamamuro T (1990) Ca, P-rich layer formed on high-strength bioactive glass-ceramic A-W. J Biomed Mater Res 24(3):331–343. doi:10.1002/jbm.820240306
Logeart-Avramoglou D, Anagnostou F, Bizios R, Petite H (2005) Engineering bone: challenges and obstacles. J Cell Mol Med 9(1):72–84
Mauney JR, Blumberg J, Pirun M, Volloch V, Vunjak-Novakovic G, Kaplan DL (2004a) Osteogenic differentiation of human bone marrow stromal cells on partially demineralized bone scaffolds in vitro. Tissue Eng 10(1–2):81–92. doi:10.1089/107632704322791727
Mauney JR, Sjostorm S, Blumberg J, Horan R, O’Leary JP, Vunjak-Novakovic G, Volloch V, Kaplan DL (2004b) Mechanical stimulation promotes osteogenic differentiation of human bone marrow stromal cells on 3-D partially demineralized bone scaffolds in vitro. Calcif Tissue Int 74(5):458–468. doi:10.1007/s00223-003-0104-7
Morone MA, Boden SD (1998) Experimental posterolateral lumbar spinal fusion with a demineralized bone matrix gel. Spine (Phila Pa 1976) 23(2):159–167
Mulliken JB, Glowacki J, Kaban LB, Folkman J, Murray JE (1981) Use of demineralized allogeneic bone implants for the correction of maxillocraniofacial deformities. Ann Surg 194(3):366–372
Mulliken JB, Kaban LB, Glowacki J (1984) Induced osteogenesis—the biological principle and clinical applications. J Surg Res 37(6):487–496
Narisawa S, Hofmann MC, Ziomek CA, Millan JL (1992) Embryonic alkaline phosphatase is expressed at M-phase in the spermatogenic lineage of the mouse. Development 116(1):159–165
Oonishi H, Kushitani S, Yasukawa E, Iwaki H, Hench LL, Wilson J, Tsuji E, Sugihara T (1997) Particulate bioglass compared with hydroxyapatite as a bone graft substitute. Clin Orthop Relat Res 334:316–325
Rosenthal RK, Folkman J, Glowacki J (1999) Demineralized bone implants for nonunion fractures, bone cysts, and fibrous lesions. Clin Orthop Relat Res 364:61–69
Sassard WR, Eidman DK, Gray PM, Block JE, Russo R, Russell JL, Taboada EM (2000) Augmenting local bone with Grafton demineralized bone matrix for posterolateral lumbar spine fusion: avoiding second site autologous bone harvest. Orthopedics 23(10):1059–1064 discussion 1064–1055
Tiedeman JJ, Garvin KL, Kile TA, Connolly JF (1995) The role of a composite, demineralized bone matrix and bone marrow in the treatment of osseous defects. Orthopedics 18(12):1153–1158
Ubhi CS, Morris DL (1984) Fracture and herniation of bowel at bone graft donor site in the iliac crest. Injury 16(3):202–203
Urist MR, Dowell TA (1968) Inductive substratum for osteogenesis in pellets of particulate bone matrix. Clin Orthop Relat Res 61:61–78
Urist MR, Strates BS (1970) Bone formation in implants of partially and wholly demineralized bone matrix. Including observations on acetone-fixed intra and extracellular proteins. Clin Orthop Relat Res 71:271–278
Urist MR, DeLange RJ, Finerman GA (1983) Bone cell differentiation and growth factors. Science 220(4598):680–686
Wheeler DL, Stokes KE, Hoellrich RG, Chamberland DL, McLoughlin SW (1998) Effect of bioactive glass particle size on osseous regeneration of cancellous defects. J Biomed Mater Res 41(4):527–533. doi:10.1002/(SICI)1097-4636(19980915)41:4<527:AID-JBM3>3.0.CO;2-E
Wheeler DL, Eschbach EJ, Hoellrich RG, Montfort MJ, Chamberland DL (2000) Assessment of resorbable bioactive material for grafting of critical-size cancellous defects. J Orthop Res 18(1):140–148. doi:10.1002/jor.1100180120
Wilson J, Pigott GH, Schoen FJ, Hench LL (1981) Toxicology and biocompatibility of bioglasses. J Biomed Mater Res 15(6):805–817. doi:10.1002/jbm.820150605
Xynos ID, Edgar AJ, Buttery LD, Hench LL, Polak JM (2000a) 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 276(2):461–465. doi:10.1006/bbrc.2000.3503
Xynos ID, Hukkanen MV, Batten JJ, Buttery LD, Hench LL, Polak JM (2000b) Bioglass 45S5 stimulates osteoblast turnover and enhances bone formation In vitro: implications and applications for bone tissue engineering. Calcif Tissue Int 67(4):321–329. doi:10.1007/s002230001134
Xynos ID, Edgar AJ, Buttery LD, Hench LL, Polak JM (2001) Gene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass 45S5 dissolution. J Biomed Mater Res 55(2):151–157. doi:10.1002/1097-4636(200105)55:2<151:AID-JBM1001>3.0.CO;2-D
Younger EM, Chapman MW (1989) Morbidity at bone graft donor sites. J Orthop Trauma 3(3):192–195
Acknowledgments
The authors would like to thank the donors and their families for their selfless gift of tissue donation, without which this research would not have been possible. The authors would also like to thank Nanotherapeutics, Inc. for their continued support of this research.
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Kirk, J.F., Ritter, G., Waters, C. et al. Osteoconductivity and osteoinductivity of NanoFUSE® DBM. Cell Tissue Bank 14, 33–44 (2013). https://doi.org/10.1007/s10561-012-9297-1
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DOI: https://doi.org/10.1007/s10561-012-9297-1