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Demineralized Dentin Matrix (DDM) As a Carrier for Recombinant Human Bone Morphogenetic Proteins (rhBMP-2)

  • In Woong UmEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1077)

Abstract

A bone graft and bone graft substitute should have at least one of the following properties: it should be (1) osteogenic, (2) osteoinductive and/or (3) osteoconductive. In addition, bone graft substitutes should be biocompatible and bioresorbable as well as easy to use and cost effective. Autologous cancellous bone is the clinical gold standard in bone grafting procedures1, 4 and it has osteogenic, osteoinductive, and osteoconductive properties. Because of disadvantages associated with harvesting autologous bone graft material, such as requiring an additional operation and possible donor site morbidity, there is a need for an alternative in terms of enhancing the bone healing for the treatment of large bony defects. One possible option is a newly developed biomaterial, the demineralized dentin matrix (DDM). It is based on autogenous tooth dentin and is produced through demineralization. It is osteoconductive and osteoinductive due to the fact that dentin contains extracellular Type I collagen and various growth factors. Based on the demineralization process the factors stay available to the host environment. In 1965, Urist already showed the formation of ectopic bone after implanting DDM into muscle pouches in rodents. DDM is used for example in dental surgery in the treatment of extraction socket preservation and guided bone regenerations. It functions as a scaffold to support bone regeneration, but can also be used as a carrier for rhBMP-2. When DDM serves as a carrier, it combines the properties of the grafting material with those of the delivered substances. This chapter will present the experimental and clinical studies of DDM for rhBMP-2 carrier as well as alternatives of bone graft substitute.

Keywords

DDM Demineralized dentin matrix rhBMP-2 Recombinant bone morphogenetic proteins 

References

  1. 1.
    Seeherman H, Wozney J, Li R (2002) Bone morphogenetic protein delivery systems. Spine (Phila Pa 1976) 27(16 Suppl 1):S16–S23CrossRefGoogle Scholar
  2. 2.
    Babensee JE, McIntire LV, Mikos AG (2000) Growth factor delivery for tissue engineering. Pharm Res 17(5):497–504CrossRefGoogle Scholar
  3. 3.
    Kirker-Head CA (2000) Potential applications and delivery strategies for bone morphogenetic proteins. Adv Drug Deliv Rev 43(1):65–92CrossRefGoogle Scholar
  4. 4.
    Li RH, Wozney JM (2001) Delivering on the promise of bone morphogenetic proteins. Trends Biotechnol 19(7):255–265CrossRefGoogle Scholar
  5. 5.
    Maeda M, Tani S, Sano A, Fujioka K (1999) Microstructure and release characteristics of the minipellet, a collagen-based drug delivery system for controlled release of protein drugs. J Control Release 62(3):313–324CrossRefGoogle Scholar
  6. 6.
    Dahners LE, Jacobs RR (1985) Long bone defects treated with demineralized bone. South Med J 78(8):933–934CrossRefGoogle Scholar
  7. 7.
    Martin GJ Jr, Boden SD, Titus L, Scarborough NL (1999) New formulations of demineralized bone matrix as a more effective graft alternative in experimental posterolateral lumbar spine arthrodesis. Spine (Phila Pa 1976) 24(7):637–645CrossRefGoogle Scholar
  8. 8.
    Urist MR (1965) Bone: formation by autoinduction. Science 150(3698):893–899CrossRefGoogle Scholar
  9. 9.
    Dinopoulos HTH, Giannoudis PV (2006) Safety and efficacy of use of demineralised bone matrix in orthopaedic and trauma surgery. Expert Opin Drug Saf 5(6):847–866.  https://doi.org/10.1517/14740338.5.6.847 CrossRefPubMedGoogle Scholar
  10. 10.
    Reddi AH (1998) Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nat Biotechnol 16(3):247–252CrossRefGoogle Scholar
  11. 11.
    Bormann N, Schwabe P, Smith MD, Wildemann B (2014) Analysis of parameters influencing the release of antibiotics mixed with bone grafting material using a reliable mixing procedure. Bone 59:162–172.  https://doi.org/10.1016/j.bone.2013.11.005. Epub 2013 Nov 12CrossRefGoogle Scholar
  12. 12.
    Elisabeth H, Pobloth A-M, Bormann N, Kolarczik N, Schmidt-Bleek K, Schell H, Schwabe P, Duda GN, Wildemann B (2017) Demineralized bone matrix as a carrier for bone morphogenetic Protein-2: burst release combined with long-term binding and Osteoinductive activity evaluated In Vitro and In Vivo. Tissue Eng Part A 23(23–24):1321–1330.  https://doi.org/10.1089/ten.tea.2017.0005 CrossRefGoogle Scholar
  13. 13.
    Brekke JH, Toth JM (1998) Principles of tissue engineering applied to programmable osteogenesis. J Biomed Mater Res 43(4):380–398CrossRefGoogle Scholar
  14. 14.
    Burg KJ, Porter S, Kellam JF (2000) Biomaterial developments for bone tissue engineering. Biomaterials 21(23):2347–2359CrossRefGoogle Scholar
  15. 15.
    Friess W (2000) Drug delivery systems based on Collagen,Berichte aus der Pharmazie. Shaker Verlag, Aachen, pp 94–137Google Scholar
  16. 16.
    Bouxsein ML, Turek TJ, Blake CA, D’Augusta D, Li X, Stevens M, Seeherman HJ, Wozney JM (2001) Recombinant human bone morphogenetic protein-2 accelerates healing in a rabbit ulnar osteotomy model. J Bone Joint Surg Am 83-A(8):1219–1230CrossRefGoogle Scholar
  17. 17.
    Boyne PJ, Lilly LC, Marx RE, Moy PK, Nevins M, Spagnoli DB, Triplett RG (2005) De novo bone induction by recombinant human bone morphogenetic protein-2 (rhBMP-2) in maxillary sinus floor augmentation. J Oral Maxillofac Surg 63(12):1693–1707CrossRefGoogle Scholar
  18. 18.
    Itoh K, Udagawa N, Katagiri T, Iemura S, Ueno N, Yasuda H, Higashio K, Quinn JM, Gillespie MT, Martin TJ, Suda T, Takahashi N (2001) Bone morphogenetic protein 2 stimulates osteoclast differentiation and survival supported by receptor activator of nuclear factor-kappaB ligand. Endocrinology 142(8):3656–3662CrossRefGoogle Scholar
  19. 19.
    Fiorellini JP, Howell TH, Cochran D, Malmquist J, Lilly LC, Spagnoli D, Toljanic J, Jones A, Nevins M (2005) Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation. J Periodontol 76(4):605–613CrossRefGoogle Scholar
  20. 20.
    Benglis D, Wang MY, Levi AD (2008) A comprehensive review of the safety profile of bone morphogenetic protein in spine surgery. Neurosurgery 62(5 Suppl 2):ONS423–ONS431.  https://doi.org/10.1227/01.neu.0000326030.24220.d8. discussion ONS431CrossRefGoogle Scholar
  21. 21.
    Ripamonti U, Duarte R, Ferretti C (2014) Re-evaluating the induction of bone formation in primates. Biomaterials 35(35):9407–9422.  https://doi.org/10.1016/j.biomaterials.2014.07.053. Epub 2014 Aug 23CrossRefGoogle Scholar
  22. 22.
    Seeherman H, Li R, Bouxsein M, Kim H, Li XJ, Smith-Adaline EA, Aiolova M, Wozney JM (2006) rhBMP-2/calcium phosphate matrix accelerates osteotomy-site healing in a nonhuman primate model at multiple treatment times and concentrations. J Bone Joint Surg Am 88(1):144–160PubMedGoogle Scholar
  23. 23.
    Murata M (2012) Collagen biology for bone regenerative surgery. J Korean Assoc Oral Maxillofac Surg 38:321–325.  https://doi.org/10.5125/jkaoms.2012.38.6.321 CrossRefGoogle Scholar
  24. 24.
    Kim YK, Kim SG, Byeon JH, Lee HJ, Um IU, Lim SC, Kim SY (2010) Development of a novel bone grafting material using autogenous teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109(4):496–503.  https://doi.org/10.1016/j.tripleo.2009.10.017. Epub 2010 Jan 8CrossRefGoogle Scholar
  25. 25.
    Tay FR, Pashley DH (2008) Guided tissue remineralisation of partially demineralised human dentine. Biomaterials 29(8):1127–1137CrossRefGoogle Scholar
  26. 26.
    Tay FR, Pashley DH (2009) Biomimetic remineralization of resin-bonded acid-etched dentin. J Dent Res 88(8):719–724.  https://doi.org/10.1177/0022034509341826 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Huang GT, Shagramanova K, Chan SW (2006) Formation of odontoblast-like cells from cultured human dental pulp cells on dentin in vitro. J Endod 32(11):1066–1073CrossRefGoogle Scholar
  28. 28.
    Marshall GW Jr, Marshall SJ, Kinney JH, Balooch M (1997) The dentin substrate: structure and properties related to bonding. J Dent 25(6):441–458CrossRefGoogle Scholar
  29. 29.
    Schilke R, Lisson JA, Bauss O, Geurtsen W (2000) Comparison of the number and diameter of dentinal tubules in human and bovine dentine by scanning electron microscopic investigation. Arch Oral Biol 45(5):355–361CrossRefGoogle Scholar
  30. 30.
    Um IW, Cho WJ, Kim YK (2015) Experimental study on human DemineralizedDentin matrix as rhBMP-2 carrier In Vivo. J Dent App 2(7):269–273Google Scholar
  31. 31.
    Bang G, Urist MR (1967) Bone induction in excavation chambers in matrix of decalcified dentin. Arch Surg 94(6):781–789CrossRefGoogle Scholar
  32. 32.
    Butler WT, Mikulski A, Urist MR, Bridges G, Uyeno S (1977) Noncollagenous proteins of a rat dentin matrix possessing bone morphogenetic activity. J Dent Res 56(3):228–232CrossRefGoogle Scholar
  33. 33.
    Yeomans JD, Urist MR (1967) Bone induction by decalcified dentine implanted into oral, osseous and muscle tissues. Arch Oral Biol 12(8):999–1008CrossRefGoogle Scholar
  34. 34.
    Um IW, Hwang SH, Kim YK, Kim MY, Jun SH, Ryu JJ, Jang HS (2016) Demineralized dentin matrix combined with recombinant human bone morphogenetic protein-2 in rabbit calvarial defects. J Korean Assoc Oral Maxillofac Surg 42(2):90–98.  https://doi.org/10.5125/jkaoms.2016.42.2.90. Epub 2016 Apr 27CrossRefGoogle Scholar
  35. 35.
    Kim KW (2014) Bone induction by demineralized dentin matrix in nude mouse muscles. Maxillofac Plast Reconstr Surg 36(2):50–56.  https://doi.org/10.14402/jkamprs.2014.36.2.50. Epub 2014 Mar 30CrossRefGoogle Scholar
  36. 36.
    Kim YK, Lee JH, Kim KW, Um IW, Murata M, Ito K (2013) Analysis of organic components and osteoinductivity in autogenous tooth bone graft material. J Korean Assoc Maxillofac Plast Reconstr Surg 35(6):353–359CrossRefGoogle Scholar
  37. 37.
    Kim YK, Lee JK, Kim KW, Um IW, Murata M (2013) Chapter 16: Advances in biomaterials science and biomedical applications. In: Pignatello R (ed) Healing mechanism and clinical application of autogenous tooth bone graft material. InTech, Rijeka, p 405Google Scholar
  38. 38.
    Kim YK, Kim SG, Bae JH, Um IW, Oh JS, Jeong KI (2014) Guided bone regeneration using autogenous tooth bone graft in implant therapy: case series. Implant Dent 23(2):138–143.  https://doi.org/10.1097/ID.0000000000000046 CrossRefPubMedGoogle Scholar
  39. 39.
    Kim YK, Kim SG, Yun PY, Yeo IS, Jin SC, Oh JS, Kim HJ, Yu SK, Lee SY, Kim JS, Um IW, Jeong MA, Kim GW (2014) Autogenous teeth used for bone grafting: a comparison with traditional grafting materials. Oral Surg Oral Med Oral Pathol Oral Radiol 117(1):e39–e45.  https://doi.org/10.1016/j.oooo.2012.04.018. Epub 2012 Aug 30CrossRefGoogle Scholar
  40. 40.
    Kim YK, Um IW, An HJ, Kim KW, Hong KS, Murata M (2014) Effects of demineralized dentin matrix used as an rhBMP-2 carrier for bone regeneration. J Hard Tissue Biol 23(4):415–422CrossRefGoogle Scholar
  41. 41.
    Kim YK, Um IW, Murata M (2014) Tooth bank system for bone regeneration -safety report. J Hard Tissue Biol 23:371–376CrossRefGoogle Scholar
  42. 42.
    Kim YK, Kim SG, Oh JS, Jin SC, Son JS, Kim SY, Lim SY (2011) Analysis of the inorganic component of autogenous tooth bone graft material. J Nanosci Nanotechnol 11(8):7442–7445CrossRefGoogle Scholar
  43. 43.
    Huggins CB, Urist MR (1970) Dentin matrix transformation: rapid induction of alkaline phosphatase and cartilage. Science 167(3919):896–898CrossRefGoogle Scholar
  44. 44.
    Huggins C, Wiseman S, Reddi AH (1970) Transformation of fibroblasts by allogeneic and xenogeneic transplants of demineralized tooth and bone. J Exp Med 132(6):1250–1258CrossRefGoogle Scholar
  45. 45.
    Murata M, Akazawa T, Takahata M, Ito M, Tazaki J, Hino J, Nakamura K, Iwasaki N, Shibata T, Arisue M (2010) Bone induction of human tooth and bone crushed by newly developed automatic mill. J Ceram Soc Jpn 118(6):434CrossRefGoogle Scholar
  46. 46.
    Kim YK, Jang HJ, Um IW (2016) A case report of allogenic demineralized dentin matrix loaded with recombinant human bone morphogenetic proteins for alveolar bone repair. J Dent Oral Health 2(6):45Google Scholar
  47. 47.
    Kim YK, Lee JH, Um IW, Cho WJ (2016) Guided bone regeneration using demineralized dentin matrix: long-term follow-up. J Oral Maxillofac Surg 74(3):515.e1–515.e9.  https://doi.org/10.1016/j.joms.2015.10.030. Epub 2015 Nov 10CrossRefGoogle Scholar
  48. 48.
    Pang KM, Um IW, Kim YK, Woo JM, Kim SM, Lee JH (2017) Autogenous demineralized dentin matrix from extracted tooth for the augmentation of alveolar bone defect: a prospective randomized clinical trial in comparison with anorganic bovine bone. Clin Oral Implants Res 28(7):809–815.  https://doi.org/10.1111/clr.12885. Epub 2016 Jun 8CrossRefGoogle Scholar
  49. 49.
    Kim YK, Pang KM, Yun PY, Leem DH, Um IW (2017) Long-term follow-up of autogenous tooth bone graft blocks with dental implants. Clin Case Rep 5(2):108–118.  https://doi.org/10.1002/ccr3.754. eCollection 2017 FebCrossRefGoogle Scholar
  50. 50.
    Ike M, Urist MR (1998) Recycled dentin root matrix for a carrier of recombinant human bone morphogenetic protein. J Oral Implantol 24(3):124–132CrossRefGoogle Scholar
  51. 51.
    Murata M (2005) Bone engineering using human demineralized dentin matrix and recombinant human BMP-2. J Hard Tissue Biol 14(2):80–81CrossRefGoogle Scholar
  52. 52.
    Um IW, Jun SH, Yun PY, Kim YK (2017) Histological comparison of autogenous and allogenic demineralized dentin matrix loaded with recombinant human bone morphogenetic Protein-2 for alveolar bone repair: a preliminary report. J Hard Tissue Biol 26(4):417–424CrossRefGoogle Scholar
  53. 53.
    Um IW, Kim YK, Mitsugi M (2017) Demineralized dentin matrix scaffolds for alveolar bone engineering. J Indian Prosthodont Soc 17(2):120–127.  https://doi.org/10.4103/jips.jips_62_17 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Kim SY, Kim YK, Park YH, Park JC, Ku JK, Um IW, Kim JY (2017) Evaluation of the healing potential of demineralized dentin matrix fixed with recombinant human bone morphogenetic Protein-2 in bone grafts. Materials (Basel) 10(9):E1049.  https://doi.org/10.3390/ma10091049 CrossRefGoogle Scholar
  55. 55.
    Lee HJ, Hong JS, Kim YK, Um IW, Lee JI (2017) Osteogenic potential of demineralized dentin matrix as bone graft material. J Hard Tissue Biol 26(2):223–230CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.R&D Institute of Korea Tooth BankSeoulSouth Korea

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