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Clinical Oral Investigations

, Volume 20, Issue 8, pp 2259–2265 | Cite as

Osteoinductive potential of 4 commonly employed bone grafts

  • Richard J. MironEmail author
  • Qiao Zhang
  • Anton Sculean
  • Daniel Buser
  • Benjamin E. Pippenger
  • Michel Dard
  • Yoshinori Shirakata
  • Fatiha Chandad
  • Yufeng ZhangEmail author
Original Article

Abstract

Objectives

Guided bone regeneration (GBR) aims to predictably restore missing bone that has been lost due to trauma, periodontal disease or a variety of systemic conditions. Critical to this procedure is the ability of a bone grafting material to predictably serve as a 3-dimensional scaffold capable of inducing cell and bone tissue in-growth at the material surface. Although all bone grafts are osteoconductive to bone-forming osteoblasts, only a small number of commercially available bone grafts with FDA approval are osteoinductive including demineralized freeze-dried bone allographs (DFDBA) and scaffolds containing bone morphogenetic proteins (BMPs). Recently, a class of synthetic bone grafts fabricated from biphasic calcium phosphate (BCP) sintered at a low temperature have been shown to form ectopic bone formation in non-skeletal sites without the use of growth factors. Therefore, the present study aimed to compare the osteoinductive potential of this group of synthetic BCP alloplasts with autografts, allografts and xenografts.

Materials and methods

In the present study, 4 types of bone grafting materials including autogenous bone harvested with a bone mill, DFDBA (LifeNet, USA), a xenograft derived from bovine bone mineral (NBM, BioOss, Geistlich, Switzerland) and a novel synthetic biphasic calcium phosphate (BCP, Straumman, Switzerland) were implanted into intramuscular pouches of 24 rats and analysed histologically for their ability to form ectopic bone formation around grafting particles. A semi-quantitative osteoinductive score was used to quantify the osteoinductive ability of each bone graft.

Results

The results from the present study reveal that (1) autogenous bone resorbed rapidly in vivo, (2) the xenograft showed no potential to form ectopic bone formation and (3) both DFDBA and BCP were able to stimulate ectopic bone formation.

Conclusion

These studies demonstrate that these newly developed synthetic bone grafts have potential for inducing ectopic bone formation similar to DFDBA. Future clinical testing is necessary to reveal their bone-inducing properties in clinical scenarios including GBR procedures and in combination with implant dentistry.

Clinical relevance

Novel BCP scaffolds are able to induce ectopic bone formation without the use of osteoinductive growth factors such as BMP2 and thus demonstrate a large clinical possibility to further enhance bone formation for a variety of clinical procedures.

Keywords

Osteoinduction Osteoinductive potential Bone grafts Natural bone mineral 

Notes

Compliance with ethical standards

Conflict of interest

BCP grafts were kindly provided by Straumann AG, Switzerland. Benjamin Pippenger and Michel Dard are both employees of Straumann AG who contributed to the experimental design and provided the bone grafting materials. All other authors declare no conflict of interest.

Funding

This study was supported by a grant from the American Academy of Implant Dentistry to Richard J. Miron (2013).

Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed by the University of Wuhan, Department of Oral Implantology, China.

Informed consent

No informed patient consent was necessary.

References

  1. 1.
    Jensen SS, Bornstein MM, Dard M, Bosshardt DD, Buser D (2009) Comparative study of biphasic calcium phosphates with different HA/TCP ratios in mandibular bone defects. A long-term histomorphometric study in minipigs. J Biomed Mater Res B Appl Biomater 90:171–181. doi: 10.1002/jbm.b.31271 PubMedGoogle Scholar
  2. 2.
    Mazock JB, Schow SR, Triplett RG (2004) Proximal tibia bone harvest: review of technique, complications, and use in maxillofacial surgery. Int J Oral Maxillofac Implants 19:586–593PubMedGoogle Scholar
  3. 3.
    Jakse N, Seibert FJ, Lorenzoni M, Eskici A, Pertl C (2001) A modified technique of harvesting tibial cancellous bone and its use for sinus grafting. Clin Oral Implants Res 12:488–494CrossRefPubMedGoogle Scholar
  4. 4.
    Giannoudis PV, Dinopoulos H, Tsiridis E (2005) Bone substitutes: an update. Injury 36(Suppl 3):S20–S27. doi: 10.1016/j.injury.2005.07.029 CrossRefPubMedGoogle Scholar
  5. 5.
    Miron RJ, Zhang YF (2012) Osteoinduction: a review of old concepts with new standards. J Dent Res 91:736–744. doi: 10.1177/0022034511435260 CrossRefPubMedGoogle Scholar
  6. 6.
    Urist MR, Silverman BF, Buring K, Dubuc FL, Rosenberg JM (1967) The bone induction principle. Clin Orthop Relat Res 53:243–283CrossRefPubMedGoogle Scholar
  7. 7.
    Urist MR (1965) Bone: formation by autoinduction. Sci (New York, NY) 150:893–899CrossRefGoogle Scholar
  8. 8.
    Urist MR, Strates BS (1971) Bone morphogenetic protein. J Dent Res 50:1392–1406CrossRefPubMedGoogle Scholar
  9. 9.
    Yuan H, Fernandes H, Habibovic P, de Boer J, Barradas AM, de Ruiter A, Walsh WR, van Blitterswijk CA, de Bruijn JD (2010) Osteoinductive ceramics as a synthetic alternative to autologous bone grafting. Proc Natl Acad Sci U S A 107:13614–13619. doi: 10.1073/pnas.1003600107 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Miron RJ, Gruber R, Hedbom E, Saulacic N, Zhang Y, Sculean A, Bosshardt DD, Buser D (2012) Impact of bone harvesting techniques on cell viability and the release of growth factors of autografts. Clin Implant Dent Relat Res. doi: 10.1111/j.1708-8208.2012.00440.x PubMedGoogle Scholar
  11. 11.
    Miron RJ, Hedbom E, Saulacic N, Zhang Y, Sculean A, Bosshardt DD, Buser D (2011) Osteogenic potential of autogenous bone grafts harvested with four different surgical techniques. J Dent Res 90:1428–1433. doi: 10.1177/0022034511422718 CrossRefPubMedGoogle Scholar
  12. 12.
    Miron RJ, Bosshardt DD, Laugisch O, Dard M, Gemperli AC, Buser D, Gruber R, Sculean A (2013) In vitro evaluation of demineralized freeze-dried bone allograft in combination with enamel matrix derivative. J Periodontol 84:1646–1654. doi: 10.1902/jop.2013.120574 PubMedGoogle Scholar
  13. 13.
    Wei L, Miron RJ, Shi B, Zhang Y (2013) Osteoinductive and osteopromotive variability among different demineralized bone allografts. Clin Implant Dent Relat Res. doi: 10.1111/cid.12118 Google Scholar
  14. 14.
    Miron RJ, Bosshardt DD, Laugisch O, Katsaros C, Buser D, Sculean A (2012) Enamel matrix protein adsorption to root surfaces in the presence or absence of human blood. J Periodontol 83:885–892. doi: 10.1902/jop.2011.110404 CrossRefPubMedGoogle Scholar
  15. 15.
    Miron RJ, Bosshardt DD, Zhang Y, Buser D, Sculean A (2012) Gene array of primary human osteoblasts exposed to enamel matrix derivative in combination with a natural bone mineral. Clin Oral Investig. doi: 10.1007/s00784-012-0742-0 Google Scholar
  16. 16.
    Miron RJ, Wei L, Bosshardt DD, Buser D, Sculean A, Zhang Y (2014) Effects of enamel matrix proteins in combination with a bovine-derived natural bone mineral for the repair of bone defects. Clin Oral Investig 18:471–478. doi: 10.1007/s00784-013-0992-5 CrossRefPubMedGoogle Scholar
  17. 17.
    Miron RJ, Bosshardt DD, Gemperli AC, Dard M, Buser D, Gruber R, Sculean A (2014) In vitro characterization of a synthetic calcium phosphate bone graft on periodontal ligament cell and osteoblast behavior and its combination with an enamel matrix derivative. Clin Oral Investig 18:443–451. doi: 10.1007/s00784-013-0977-4 CrossRefPubMedGoogle Scholar
  18. 18.
    Zhang Y, Wei L, Miron RJ, Shi B, Bian Z (2015) Anabolic bone formation via a site-specific bone-targeting delivery system by interfering with semaphorin 4d expression. J Bone Miner Res Off J Am Soc Bone Miner Res 30:286–296. doi: 10.1002/jbmr.2322 CrossRefGoogle Scholar
  19. 19.
    Zhang Y, Wu C, Luo T, Li S, Cheng X, Miron RJ (2012) Synthesis and inflammatory response of a novel silk fibroin scaffold containing BMP7 adenovirus for bone regeneration. Bone 51:704–713. doi: 10.1016/j.bone.2012.06.029 CrossRefPubMedGoogle Scholar
  20. 20.
    Ranly DM, Lohmann CH, Andreacchio D, Boyan BD, Schwartz Z (2007) Platelet-rich plasma inhibits demineralized bone matrix-induced bone formation in nude mice. J Bone Joint Surg Am 89:139–147. doi: 10.2106/jbjs.f.00388 CrossRefPubMedGoogle Scholar
  21. 21.
    Schwartz Z, Mellonig JT, Carnes Jr DL, de la Fontaine J, Cochran DL, Dean DD, Boyan BD (1996) Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation. J Periodontol 67:918–926. doi: 10.1902/jop.1996.67.9.918
  22. 22.
    Schwartz Z, Weesner T, van Dijk S, Cochran DL, Mellonig JT, Lohmann CH, Carnes DL, Goldstein M, Dean DD, Boyan BD (2000) Ability of deproteinized cancellous bovine bone to induce new bone formation. J Periodontol 71:1258–1269. doi: 10.1902/jop.2000.71.8.1258 CrossRefPubMedGoogle Scholar
  23. 23.
    Miron RJ, Sculean A, Shuang Y, Bosshardt DD, Gruber R, Buser D, Chandad F, Zhang Y (2015) Osteoinductive potential of a novel biphasic calcium phosphate bone graft in comparison with autographs, xenografts, and DFDBA. Clin Oral Implants Res. doi: 10.1111/clr.12647 Google Scholar
  24. 24.
    Wei L, Miron RJ, Shi B, Zhang Y (2015) Osteoinductive and osteopromotive variability among different demineralized bone allografts. Clin Implant Dent Relat Res 17:533–542. doi: 10.1111/cid.12118 CrossRefPubMedGoogle Scholar
  25. 25.
    Chan O, Coathup MJ, Nesbitt A, Ho CY, Hing KA, Buckland T, Campion C, Blunn GW (2012) The effects of microporosity on osteoinduction of calcium phosphate bone graft substitute biomaterials. Acta Biomater 8:2788–2794. doi: 10.1016/j.actbio.2012.03.038 CrossRefPubMedGoogle Scholar
  26. 26.
    Coathup MJ, Hing KA, Samizadeh S, Chan O, Fang YS, Campion C, Buckland T, Blunn GW (2012) Effect of increased strut porosity of calcium phosphate bone graft substitute biomaterials on osteoinduction. J Biomed Mater Res A 100:1550–1555. doi: 10.1002/jbm.a.34094 CrossRefPubMedGoogle Scholar
  27. 27.
    Habibovic P, Gbureck U, Doillon CJ, Bassett DC, van Blitterswijk CA, Barralet JE (2008) Osteoconduction and osteoinduction of low-temperature 3D printed bioceramic implants. Biomaterials 29:944–953. doi: 10.1016/j.biomaterials.2007.10.023 CrossRefPubMedGoogle Scholar
  28. 28.
    Dahlin C, Obrecht M, Dard M, Donos N (2015) Bone tissue modelling and remodelling following guided bone regeneration in combination with biphasic calcium phosphate materials presenting different microporosity. Clin Oral Implants Res 26:814–822. doi: 10.1111/clr.12361 CrossRefPubMedGoogle Scholar
  29. 29.
    Bornstein MM, Chappuis V, von Arx T, Buser D (2008) Performance of dental implants after staged sinus floor elevation procedures: 5-year results of a prospective study in partially edentulous patients. Clin Oral Implants Res 19:1034–1043. doi: 10.1111/j.1600-0501.2008.01573.x CrossRefPubMedGoogle Scholar
  30. 30.
    Jensen SS, Aaboe M, Janner SF, Saulacic N, Bornstein MM, Bosshardt DD, Buser D (2013) Influence of particle size of deproteinized bovine bone mineral on new bone formation and implant stability after simultaneous sinus floor elevation: a histomorphometric study in minipigs. Clin Oral Implants Res. doi: 10.1111/cid.12101 PubMedGoogle Scholar
  31. 31.
    Jensen SS, Bosshardt DD, Gruber R and Buser D (2014) Long-term stability of contour augmentation in the esthetic zone. Histologic and histomorphometric evaluation of 12 human biopsies 14 to 80 months after augmentation. J Periodontol:1–15. doi: 10.1902/jop.2014.140182
  32. 32.
    Donos N, Kostopoulos L, Tonetti M, Karring T, Lang NP (2006) The effect of enamel matrix proteins and deproteinized bovine bone mineral on heterotopic bone formation. Clin Oral Implants Res 17:434–438. doi: 10.1111/j.1600-0501.2006.01260.x CrossRefPubMedGoogle Scholar
  33. 33.
    Schwartz Z, Somers A, Mellonig JT, Carnes Jr DL, Dean DD, Cochran DL, Boyan BD (1998) Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation is dependent on donor age but not gender. J Periodontol 69:470–478. doi: 10.1902/jop.1998.69.4.470
  34. 34.
    Davison NL, Gamblin AL, Layrolle P, Yuan H, de Bruijn JD, Barrere-de Groot F (2014) Liposomal clodronate inhibition of osteoclastogenesis and osteoinduction by submicrostructured beta-tricalcium phosphate. Biomaterials 35:5088–5097. doi: 10.1016/j.biomaterials.2014.03.013 CrossRefPubMedGoogle Scholar
  35. 35.
    Davison NL, Su J, Yuan H, van den Beucken JJ, de Bruijn JD, Barrere-de Groot F (2015) Influence of surface microstructure and chemistry on osteoinduction and osteoclastogenesis by biphasic calcium phosphate discs. Eur Cell Mater 29:314–329PubMedGoogle Scholar
  36. 36.
    Davison NL, ten Harkel B, Schoenmaker T, Luo X, Yuan H, Everts V, Barrere-de Groot F, de Bruijn JD (2014) Osteoclast resorption of beta-tricalcium phosphate controlled by surface architecture. Biomaterials 35:7441–7451. doi: 10.1016/j.biomaterials.2014.05.048 CrossRefPubMedGoogle Scholar
  37. 37.
    Miron RJ, Bosshardt DD (2016) OsteoMacs: key players around bone biomaterials. Biomaterials 82:1–19. doi: 10.1016/j.biomaterials.2015.12.017 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Richard J. Miron
    • 1
    • 2
    • 3
    • 4
    Email author
  • Qiao Zhang
    • 1
  • Anton Sculean
    • 3
  • Daniel Buser
    • 4
  • Benjamin E. Pippenger
    • 5
  • Michel Dard
    • 6
  • Yoshinori Shirakata
    • 7
  • Fatiha Chandad
    • 2
  • Yufeng Zhang
    • 1
    Email author
  1. 1.The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of StomatologyWuhan UniversityWuhanPeople’s Republic of China
  2. 2.Faculté de Medecine Dentaire, Pavillon de Médecine DentaireUniversité de LavalQuébecCanada
  3. 3.Department of PeriodontologyUniversity of Bern, School of Dental MedicineBernSwitzerland
  4. 4.Department of Oral Surgery and Stomatology, School of Dental MedicineUniversity of BernBernSwitzerland
  5. 5.Institut Straumann AGBaselSwitzerland
  6. 6.Department of Periodontology and Implant DentistryNew York UniversityNew YorkUSA
  7. 7.Department of PeriodontologyKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan

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