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Clinical Applications of Biomaterials pp 383–410Cite as

Development of URIST™ a Multiphasic rhBMP-2 Bone Graft Substitute

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Abstract

Recombinant human bone morphogenetic protein (BMP) containing implants can be as effective as autogenous bone grafts and have been approved clinically to stimulate spine fusion, repair of long bone non-unions and bone augmentation in the jaw.

BMP implants are expensive and are associated with complications including ectopic bone formation, inflammation and cancer due to the very high doses of BMP used. These high doses are required due to the inefficient burst release from the collagen carriers used. However, the use of traditional sustained release carriers to deliver BMP have not been successful.

We have developed a novel BMP carrier URIST which releases the BMP with an initial burst to promote mesenchymal cell recruitment followed by a sustained release. We have demonstrated in a series of non-clinical studies that URIST can produce more bone with less BMP than the currently approved collagen carrier. Further in a large animal model we demonstrate that URIST is safe and effective for alveolar ridge augmentation.

To be published in “Clinical Applications of Biomaterials: State-of-the-art progress, trends and novel approaches” Gurbinder Kaur (ed) Springer-Nature.

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References

  1. Dimitriou R, et al. Complications following autologous bone graft harvesting from the iliac crest and using the RIA: a systematic review. Injury. 2011;42(Suppl 2):S3–15.

    Article  Google Scholar 

  2. Seiler 3rd JG, Johnson J. Iliac crest autogenous bone grafting: donor site complications. J South Orthop Assoc. 2000;9(2):91–7.

    Google Scholar 

  3. Sammarco VJ, Chang L. Modern issues in bone graft substitutes and advances in bone tissue technology. Foot Ankle Clin. 2002;7(1):19–41.

    Article  Google Scholar 

  4. Szpalski M, Gunzburg R. Applications of calcium phosphate-based cancellous bone void fillers in trauma surgery. Orthopedics. 2002;25(5 Suppl):s601–9.

    Google Scholar 

  5. Rosen V. BMP-2 signalling in bone development and repair. Cytokine Growth Factor Rev. 2009;20:475–80.

    Article  Google Scholar 

  6. Yu Y, et al. TGF-beta, BMPS, and their signal transducing mediators, Smads, in rat fracture healing. J Biomed Mater Res. 2002;60(3):392–7.

    Article  Google Scholar 

  7. Li G, et al. rhBMP-2, rhVEGF(165), rhPTN and thrombin-related peptide, TP508 induce chemotaxis of human osteoblasts and microvascular endothelial cells. J Orthop Res. 2005;23(3):680–5.

    Article  Google Scholar 

  8. Lee DH, et al. Chemotactic migration of human mesenchymal stem cells and MC3T3-E1 osteoblast-like cells induced by COS-7 cell line expressing rhBMP-7. Tissue Eng. 2006;12(6):1577–86.

    Article  Google Scholar 

  9. Lane JM. Bone morphogenic protein science and studies. J Orthop Trauma. 2005;19(10 Suppl):S17–22.

    Article  Google Scholar 

  10. Khan SN, Lane JM. The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in orthopaedic applications. Expert Opin Biol Ther. 2004;4(5):741–8.

    Article  Google Scholar 

  11. Giannoudis PV, Tzioupis C. Clinical applications of BMP-7: the UK perspective. Injury. 2005;36(Suppl 3):S47–50.

    Article  Google Scholar 

  12. Cahill KS, et al. Prevalence, complications, and hospital charges associated with use of bone-morphogenetic proteins in spinal fusion procedures. JAMA. 2009;302(1):58–66.

    Article  Google Scholar 

  13. Tannoury CA, An HS. Complications with the use of bone morphogenetic protein 2 (BMP-2) in spine surgery. Spine J. 2014;14(3):552–9.

    Article  Google Scholar 

  14. Woo EJ. Recombinant human bone morphogenetic protein-2: adverse events reported to the manufacturer and user facility device experience database. Spine J. 2012;12(10):894–9.

    Article  Google Scholar 

  15. Devine JG, et al. The use of rhBMP in spine surgery: is there a cancer risk? Evid Based Spine Care J. 2012;3(2):35–41.

    Article  Google Scholar 

  16. Fu R, et al. Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion: a systematic review and meta-analysis. Ann Intern Med. 2013;158(12):890–902.

    Article  Google Scholar 

  17. Cooper GS, Kou TD. Risk of cancer after lumbar fusion surgery with recombinant human bone morphogenic protein-2 (rh-BMP-2). Spine (Phila Pa 1976). 2013;38(21):1862–8.

    Article  Google Scholar 

  18. Garrison K, et al. Clinical effectiveness and cost-effectiveness of bone morphogenetic proteins in the non-healing of fractures and spinal fusion: a systematic review. Health Technol Assess. 2007;11(30):1.

    Article  Google Scholar 

  19. Olympus Corporation. Olympus corporation announces plans to discontinue operations for its Biotechnology Division in the U.S. 2014: PR Newswire.

    Google Scholar 

  20. Barr T, et al. Comparison of the osteoinductivity of bioimplants containing recombinant human bone morphogenetic proteins 2 (Infuse) and 7 (OP-1). Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(4):531–40.

    Article  Google Scholar 

  21. De Groot K. Carriers that concentrate native bone morphogentic protein in vivo. Tissue Eng. 1998;4(4):337–41.

    Article  Google Scholar 

  22. Seeherman H, Wozney JM. Delivery of bone morphogenetic proteins for orthopedic tissue regeneration. Cytokine Growth Factor Rev. 2005;16(3):329–45.

    Article  Google Scholar 

  23. Friess W, et al. Characterization of absorbable collagen sponges as rhBMP-2 carriers. Int J Pharm. 1999;187(1):91–9.

    Article  Google Scholar 

  24. Xu SW, et al. Early period of fracture healing in ovariectomized rats. Chin J Traumatol. 2003;6(3):160–6.

    Google Scholar 

  25. Morone MA, et al. The Marshall R. Urist young investigator award. Gene expression during autograft lumbar spine fusion and the effect of bone morphogenetic protein 2. Clin Orthop Relat Res. 1998;351:252–65.

    Article  Google Scholar 

  26. Ivaska KK, et al. Effect of fracture on bone turnover markers: a longitudinal study comparing marker levels before and after injury in 113 elderly women. J Bone Miner Res. 2007;22(8):1155–64.

    Article  Google Scholar 

  27. Karladani AH, et al. The influence of fracture etiology and type on fracture healing: a review of 104 consecutive tibial shaft fractures. Arch Orthop Trauma Surg. 2001;121(6):325–8.

    Article  Google Scholar 

  28. Nakamura Y, et al. Temporal and spatial expression profiles of BMP receptors and noggin during BMP-2-induced ectopic bone formation. J Bone Miner Res. 2003;18(10):1854–62.

    Article  Google Scholar 

  29. Nakamura Y, et al. Expression profiles of BMP-related molecules induced by BMP-2 or -4 in muscle-derived primary culture cells. J Bone Miner Metab. 2005;23(6):426–34.

    Article  Google Scholar 

  30. Takayama K, et al. RNA interference for noggin enhances the biological activity of bone morphogenetic proteins in vivo and in vitro. J Bone Miner Metab. 2009;27(4):402–11.

    Article  Google Scholar 

  31. Humber CC, et al. Bone healing with an in situ-formed bioresorbable polyethylene glycol hydrogel membrane in rabbit calvarial defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(3):372–84.

    Article  Google Scholar 

  32. US Food and Drug Administration. Inactive ingredient database. 2016 [cited 2017 14 Jan]; Available from: http://www.accessdata.fda.gov/scripts/cder/iig/index.Cfm.

  33. Dumortier G, et al. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res. 2006;23:2709–28.

    Article  Google Scholar 

  34. Zhou AJ, Clokie CM, Peel SA. Bone formation in algae-derived and synthetic calcium phosphates with or without poloxamer. J Craniofac Surg. 2013;24(2):354–9.

    Article  Google Scholar 

  35. Issa JPM, et al. Bone healing process in critical-sized defects by rhBMP-2 using poloxamer gel and collagen sponge as carriers. Micron. 2008;39(1):17–24.

    Article  Google Scholar 

  36. Clokie CML, Urist MR. Bone morphogenetic protein excipients: comparative observations on poloxamer. Plast Reconstr Surg. 2000;105:628–37.

    Article  Google Scholar 

  37. Clokie CM, Bell RC. Recombinant human transforming growth factor beta-1 and its effects on osseointegration. J Craniofac Surg. 2003;14(3):268–77.

    Article  Google Scholar 

  38. Thomas MV, Puleo DA. Calcium sulfate: properties and clinical applications. J Biomed Mater Res B Appl Biomater. 2009;88(2):597–610.

    Article  Google Scholar 

  39. Lu J, et al. The biodegradation mechanism of calcium phosphate biomaterials in bone. J Biomed Mater Res. 2002;63(4):408–12.

    Article  Google Scholar 

  40. Nery EB, et al. Tissue response to biphasic calcium phosphate ceramic with different ratios of HA/beta TCP in periodontal osseous defects. J Periodontol. 1992;63(9):729–35.

    Article  Google Scholar 

  41. LeGeros RZ, et al. Biphasic calcium phosphate bioceramics: preparation, properties and applications. J Mater Sci Mater Med. 2003;14(3):201–9.

    Article  Google Scholar 

  42. Li RH, Wozney JM. Delivering on the promise of bone morphogenetic proteins. Trends Biotechnol. 2001;19(7):255–65.

    Article  Google Scholar 

  43. Sigurdsson TJ, et al. Bone morphogenetic protein-2 for peri-implant bone regeneration and osseointegration. Clin Oral Implants Res. 1997;8(5):367–74.

    Article  Google Scholar 

  44. Fiorellini JP, et al. Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation. J Periodontol. 2005;76(4):605–13.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Induce Biologics Inc., Toronto, ON, Canada

    Sean A. F. Peel Ph.D., Aileen J. J. Zhou Ph.D., Hanje Chen M.Sc. & Cameron M. L. Clokie DDS; Ph.D.

Authors
  1. Sean A. F. Peel Ph.D.
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  2. Aileen J. J. Zhou Ph.D.
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  3. Hanje Chen M.Sc.
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  4. Cameron M. L. Clokie DDS; Ph.D.
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Corresponding author

Correspondence to Sean A. F. Peel Ph.D. .

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Editors and Affiliations

  1. School of Physics and Materials Science, Thapar University, Patiala, India

    Gurbinder Kaur

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Peel, S.A.F., Zhou, A.J.J., Chen, H., Clokie, C.M.L. (2017). Development of URIST™ a Multiphasic rhBMP-2 Bone Graft Substitute. In: Kaur, G. (eds) Clinical Applications of Biomaterials. Springer, Cham. https://doi.org/10.1007/978-3-319-56059-5_12

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