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Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part A: Current challenges in BMP delivery

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Abstract

Recombinant human bone morphogenetic proteins (rhBMPs) have been extensively investigated for developing therapeutic strategies aimed at the restoration and treatment of orthopaedic as well as craniofacial conditions. In this first part of the review, we discuss the rationale for the necessary use of carrier systems to deliver rhBMP-2 and rhBMP-7 to sites of bone tissue regeneration and repair. General requirements for growth factor delivery systems emphasizing the distinction between localized and release-controlled delivery strategies are presented highlighting the current limitations in the development of an effective rhBMP delivery system applicable in clinical bone tissue engineering.

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References

  • Bessa PC, Casal M, Reis RL (2008) Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts). J Tissue Eng Regen Med 2:1–13

    Article  PubMed  CAS  Google Scholar 

  • Bishop GB, Einhorn TA (2007) Current and future clinical applications of bone morphogenetic proteins in orthopaedic trauma surgery. Int Orthop 31(6):721–727

    Article  PubMed  Google Scholar 

  • Boden SD, Kang J, Sandhu HS, Heller JG (2002) Use of rhBMP2 to achieve posterolateral lumbar spine fusion in humans: a prospective randomized clinical trial. Spine 27:2662–2673

    Article  PubMed  Google Scholar 

  • Chen RR, Mooney DJ (2002) Polymeric growth factor delivery strategies for tissue engineering. Pharm Res 20:1103–1112

    Article  Google Scholar 

  • Cho CH, Nuttall ME (2002) Emerging techniques for the discovery and validation of therapeutic targets for skeletal diseases. Expert Opin Ther Targets 6:679–689

    Article  PubMed  CAS  Google Scholar 

  • Dard M, Sewing A, Meyer J, Verrier S, Roessler S, Scharnweber D (2000) Tools for tissue engineering of mineralized oral structures. Clin Oral Invest 4:126–129

    Article  CAS  Google Scholar 

  • Demers CN, Tabrizian M, Petit A, Hamdy RC, Yahia L (2002) Effect of experimental parameters on the in vitro release kinetics of transforming growth factor beta1 from coral particles. J Biomed Mater Res 59:403–410

    Article  PubMed  CAS  Google Scholar 

  • Einhorn TA (2003) Clinical applications of recombinant human BMPs: early experience and future development. J Bone Joint Surg Am 85-A:82–88

    PubMed  Google Scholar 

  • Einhorn TA, Majeska RJ, Mohaideen A, Bouxsein ML, Turek TJ, Wozney JM (2003) A single percutaneous injection of rhBMP-2 accelerates fracture repair. J Bone Joint Surg Am 85-A:1425–1435

    PubMed  Google Scholar 

  • Engstrand T, Veltheim R, Arnander C, Docherty-Skogh AC, Westermark A, Ohlsson C, Adolfsson L, Larm O (2008) A novel biodegradable delivery system for bone morphogenetic protein-2. Plast Reconstr Surg 121:1920–1928

    Article  PubMed  CAS  Google Scholar 

  • Friedlaender GE, Perry CR, Cole JD, Cook SD, Cierny G, Muschler GF et al (2001) Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 83-A:151–158

    Google Scholar 

  • Gautschi OP, Frey SP, Zellweger R (2003) Bone morphogenetic proteins in clinical applications. ANZ J Surg 77:626–631

    Article  Google Scholar 

  • Geiger M, Li RH et al (2003) Collagen sponges for bone regeneration with rhBMP-2. Adv Drug Deliv Rev 55:1613–1629

    Article  PubMed  CAS  Google Scholar 

  • Giannoudis PV, Einhorn TA, Marsh D (2007) Fracture healing: the diamond concept. Injury 38(S4):3–6

    Article  Google Scholar 

  • Haidar ZS, Hamdy RC, Tabrizian M (2008a) Protein release kinetics for core-shell hybrid nanoparticles based on the layer-by-layer assembly of alginate and chitosan on liposomes. Biomaterials 29:1207–1215

    Article  PubMed  CAS  Google Scholar 

  • Haidar ZS, Azari F, Hamdy RC, Tabrizian M (2008b) Modulated release of OP-1 and enhanced pre-osteoblast differentiation using a core-shell nanoparticulate system. J Biomed Mater Res A (in press)

  • Haidar ZS, Tabrizian M, Hamdy RC (2009) A hybrid OP-1 delivery system enhances new bone regeneration and consolidation in a rabbit model of distraction osteogenesis. Growth Factors (in press)

  • Hamdy RC, Amako M, Beckman L, Kawaguchi M, Rauch F, Lauzier D, Steffen T (2003) Effects of osteogenic protein-1 on distraction osteogenesis in rabbits. Bone 33:248–255

    Article  PubMed  CAS  Google Scholar 

  • Hollinger JO, Schmitt JM, Buck DC, Shannon R, Joh SP, Zegzula HD, Wozney J (1998) Recombinant human bone morphogenetic protein-2 and collagen for bone regeneration. J Biomed Mater Res 43:356–364

    Article  PubMed  CAS  Google Scholar 

  • Hosseinkhani H, Hosseinkhani M, Tian F, Kobayashi H, Tabata Y (2007) Bone regeneration on a collagen sponge self-assembled peptide-amphiphile nanofiber hybrid scaffold. Tissue Eng 13:11–19

    Article  PubMed  CAS  Google Scholar 

  • Hou Q, De Bank PA, Shakesheff KM (2004) Injectable scaffolds for tissue regeneration. J Mater Chem 14:1915–1923

    Article  CAS  Google Scholar 

  • Issa JP, Bentley MV, Iyomasa MM, Sebald W, De Albuquerque RF (2008) Sustained release carriers used to delivery bone morphogenetic proteins in the bone healing process. Anat Histol Embryol 37:181–187

    Article  PubMed  CAS  Google Scholar 

  • Jeon O, Song SJ, Yang HS, Bhang SH, Kang SW et al (2008) Long-term delivery enhances in vivo osteogenic efficacy of BMP-2 compared to short-term delivery. Biochem Biophys Res Commun 369:774–780

    Article  PubMed  CAS  Google Scholar 

  • Kimelman N, Pelled G, Helm GA, Huard J, Schwarz EM, Gazit D (2007) Review: gene- and stem cell-based therapeutics for bone regeneration and repair. Tissue Eng 13:1135–1150

    Article  PubMed  CAS  Google Scholar 

  • Kirker-Head CA (2000) Potential applications and delivery strategies for bone morphogenetic proteins. Adv Drug Deliv Rev 43:65–92

    Article  PubMed  CAS  Google Scholar 

  • Lee SH, Shin H (2007) Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. Adv Drug Deliv Rev 59(4–5):339–359

    Article  PubMed  CAS  Google Scholar 

  • Li RH, Wozney JM (2001) Delivering on the promise of bone morphogenetic proteins. Trend Biotechnol 19:255–265

    Article  CAS  Google Scholar 

  • Luginbuehl V, Meinel L et al (2004) Localized delivery of growth factors for bone repair. Eur J Pharm Biopharm 58:197–208

    Article  PubMed  CAS  Google Scholar 

  • Mandu-Hrit M, Haque T, Lauzier D, Kotsiopriftis M, Rauch F, Tabrizian M, Henderson JE, Hamdy RC (2006) Early injection of OP-1 during distraction osteogenesis accelerates new bone formation in rabbits. Growth Factors 24:172–183

    Article  PubMed  CAS  Google Scholar 

  • Mont MA, Ragland PS, Biggins B, Friedlaender G et al (2004) Use of bone morphogenetic proteins for musculoskeletal applications. An overview. J Bone Joint Surg 86:41–55

    PubMed  Google Scholar 

  • Paramore CG, Lauryssen C, Rauzzino MJ, Wadlington VR et al (1999) The safety of OP-1 for lumbar fusion with decompression: a canine study. Neurosurgery 44:1151–1156

    Article  PubMed  CAS  Google Scholar 

  • Prabaharan M (2008) Chitosan derivatives as promising materials for controlled drug delivery. J Biomater Appl 23:5–36

    Article  PubMed  CAS  Google Scholar 

  • Raiche T, Puleo A (2004) In vitro effects of combined and sequential delivery of two bone growth factors. Biomaterials 25:677–685

    Article  PubMed  CAS  Google Scholar 

  • Reddi AH (2005) BMPs: from bone morphogenetic proteins to body morphogenetic proteins. Cytokine Growth Fact Rev 16:249–250

    Article  CAS  Google Scholar 

  • Ripamonti U, Van Den Heever B, Crooks J, Tucker MM, Sampath TK, Rueger DC, Reddi AH (2000) Long-term evaluation of bone formation by osteogenic protein 1 in the baboon and the relative efficacy of bone-derived bone morphogenetic proteins delivered by irradiated xenogenic collagenous matrices. J Bone Min Res 15:1798–1809

    Article  CAS  Google Scholar 

  • Rose FR, Hou Q, Oreffo RO (2004) Delivery systems for bone growth factors—the new players in skeletal regeneration. J Pharm Pharmacol 56:415–427

    Article  PubMed  CAS  Google Scholar 

  • Saito K, Konishi I, Nishiguchi M, Hoshino T, Fujiwara T (2008) Amelogenin binds to both heparan sulfate and bone morphogenetic protein 2 and pharmacologically suppresses the effect of noggin. Bone 43:371–376

    Article  PubMed  CAS  Google Scholar 

  • Seeherman H, Wozney JM (2005) Delivery of bone morphogenetic proteins for orthopedic tissue regeneration. Cytokine Growth Factor Rev 16:329–345

    Article  PubMed  CAS  Google Scholar 

  • Talwar R, Di Silvio L, Hughes FJ, King GN (2001) Effects of carrier release kinetics on bone morphogenetic protein-2-induced periodontal regeneration in vivo. J Clin Periodontol 28:340–347

    Article  PubMed  CAS  Google Scholar 

  • Termaat MF, Den Boer FC, Bakker FC, Patka P, Haarman HJ (2005) Bone morphogenetic proteins. Development and clinical efficacy in the treatment of fractures and bone defects. J Bone Joint Surg Am 87:1367–1378

    Article  PubMed  CAS  Google Scholar 

  • Ueda H, Hong L, Yamamoto M, Shigeno K, Inoue M et al (2002) Use of collagen sponge incorporating transforming growth factor-beta1 to promote bone repair in skull defects in rabbits. Biomaterials 23:1003–1010

    Article  PubMed  CAS  Google Scholar 

  • Uludag H, Gao T, Porter TJ, Friess W, Wozney JM (2001) Delivery systems for BMPs: factors contributing to protein retention at an application site. J Bone Joint Surg Am 83-A:128–135

    Google Scholar 

  • Vaccaro AR, Whang PG, Patel T, Phillips FM et al (2008) The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study. Spine J 8:457–465

    Article  PubMed  Google Scholar 

  • Vonau RL, Bostrom MP, Aspenberg P, Sams AE (2001) Combination of growth factors inhibits bone ingrowth in the bone harvest chamber. Clin Orthop Relat Res 386:243–251

    Article  PubMed  Google Scholar 

  • Weinstein SL (2000) 2000–2010: the bone and joint decade. J Bone Joint Surg Am 82:1–3

    Article  PubMed  CAS  Google Scholar 

  • Westerhuis RJ, van Bezooijen RL et al (2005) Use of bone morphogenetic proteins in traumatology. Injury 36:1405–1412

    Article  PubMed  CAS  Google Scholar 

  • Whang K, Tsai DC, Nam EK, Aitken M, Sprague SM, Patel PK, Healy KE (2000) Ectopic bone formation via rhBMP-2 delivery from porous bioabsorbable polymer scaffolds. J Biomed Mater Res 42:491–499

    Article  Google Scholar 

Download references

Acknowledgments

The authors wish to thank grants from the Shriners of North America, Fonds de la Recherche en Santé du Québec, the National Science and Engineering Research Council, the Canadian Institutes of Health Research (CIHR)—Regenerative Medicine/Nanomedicine and the Center for Biorecognition and Biosensors (CBB), McGill University, Montréal, Québec, Canada. Dr. Haidar acknowledges scholarships from the Center for Bone and Periodontal Diseases Research and the Shriners Hospital, Montréal, Québec, Canada.

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Authors and Affiliations

  1. Faculty of Dentistry, McGill University, 740 Rue Dr. Penfield Suite # 4300, Montréal, QC, H3A 1A4, Canada

    Ziyad S. Haidar & Maryam Tabrizian

  2. Department of Biomedical Engineering, Faculty of Medicine, McGill University, Montréal, QC, Canada

    Ziyad S. Haidar & Maryam Tabrizian

  3. Center for Biorecognition and Biosensors, McGill University, 3775 University Street, Montréal, QC, H3A 2B4, Canada

    Ziyad S. Haidar, Reggie C. Hamdy & Maryam Tabrizian

  4. Shriners Hospital for Children and Division of Orthopaedics, Montreal Children’s Hospital, McGill University, 1529 Cedar Avenue, Montréal, QC, H3A 1A6, Canada

    Ziyad S. Haidar & Reggie C. Hamdy

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  1. Ziyad S. Haidar
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  2. Reggie C. Hamdy
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  3. Maryam Tabrizian
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Correspondence to Maryam Tabrizian.

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Haidar, Z.S., Hamdy, R.C. & Tabrizian, M. Delivery of recombinant bone morphogenetic proteins for bone regeneration and repair. Part A: Current challenges in BMP delivery. Biotechnol Lett 31, 1817–1824 (2009). https://doi.org/10.1007/s10529-009-0099-x

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  • DOI: https://doi.org/10.1007/s10529-009-0099-x

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