Skip to main content
SpringerLink
Log in

Essential Requirements for Resorbable Bioceramic Development: Research, Manufacturing, and Preclinical Studies

  • Reference work entry
  • First Online:
Handbook of Bioceramics and Biocomposites

  • 3044 Accesses

Abstract

There is a large variety of commercial bioceramic bone substitutes; however, the prerequisites for bone reconstruction and tissue engineering are often absent in research and clinical applications. The main criteria for the use of bioceramics are easily handled biomaterials that are solid, injectable, and/or shapeable. Furthermore, the material must have the appropriate osteoconductive and osteoinductive properties. New bone regeneration technologies, such as “smart matrices,” must be developed and optimized to increase their suitability for bone defects and to support suitable Ortho Biology. This contribution presents the basic smart bone substitutes used for bone regeneration, which will support the twenty-first-century challenge in osteoarticular pathology to replace autografts with more efficient synthetic materials. The paper is focused on the specifications required for the smart matrix (or osteo instructive matrix), the needs of the surgeon, the clinical indications, the regulatory constraints, and product development and marketing. Finally, an example was presented of a smart matrix medical device developed and used in bone regeneration and details the cascade of steps necessary to put it on the market: research and development, meeting the regulatory criteria, preclinical and clinical data, CE mark approval, and FDA (United States Federal Drug Administration).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 699.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 699.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Planell JA et al (2009) Bone repair biomaterials. Elsevier, CRC Press, Boca Raton, Woohead Pub Limited Oxford

    Google Scholar 

  2. Williams D (2014) Essential biomaterials science. Cambridge University Press, Cambridge/New York

    Google Scholar 

  3. Daculsi G, Baroth S, Sensebe L, Rosset P, Durand M, Boisteau O, Layrolle P (2013) Association of cells and biomaterials for bone reconstruction. IRBM 32:76–79

    Article  Google Scholar 

  4. Rosset P, Deschaseaux F, Layrolle P (2014) Cell therapy for bone repair. Orthop Traumatol Surg Res 100:S107–S112

    Article  Google Scholar 

  5. Daculsi G et al (2013) Osteoconduction, osteogenicity, osteoinduction, what are the fundamental properties for a smart bone substitutes. IRBM 34:346–348

    Article  Google Scholar 

  6. Wilson-Hench J (1987) Osteoinduction. Prog Biomed Eng 4:29

    Google Scholar 

  7. Giannoudis PV, Einhorn TA, Marsh D (2007) Fracture healing: the diamond concept. Injury 38:S3–S6

    Article  Google Scholar 

  8. Fellah BH et al (2008) Osteogenicity of biphasic calcium phosphate ceramics and bone autograft in a goat model. Biomaterials 29:1177–1188

    Article  Google Scholar 

  9. Yuan H et al (2006) Cross-species comparison of ectopic bone formation in biphasic calcium phosphate (BCP) and hydroxyapatite (HA) scaffolds. Tissue Eng 12:1607–1615

    Article  Google Scholar 

  10. Habibovic P, de Groot K (2007) Osteoinductive biomaterials – properties and relevance in bone repair. J Tissue Eng Regen Med 1:25–32

    Article  Google Scholar 

  11. Daculsi G, Layrolle P (2004) Osteoinductive properties of micro macroporous biphasic calcium phosphate bioceramics. Key Eng Mater 254:1005–1008

    Article  Google Scholar 

  12. Le Nihouannen D et al (2005) Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles. Bone 36:1086–1093

    Article  Google Scholar 

  13. Daculsi G et al (1990) Formation of carbonate-apatite crystals after implantation of calcium phosphate ceramics. Calcif Tissue Int 46:20–27

    Article  Google Scholar 

  14. Danet S, Haury B (2011) L’état de santé de la population en France. In: Suivi des objectifs annexés à la loi de santé publique. Dress, Paris

    Google Scholar 

  15. Stevens B et al (2008) A review of materials, fabrication methods, and strategies used to enhance bone regeneration in engineered bone tissues. J Biomed Mater Res B Appl Biomater 85:573–582

    Article  Google Scholar 

  16. Laurie SW et al (1984) Donor-site morbidity after harvesting rib and iliac bone. Plast Reconstr Surg 73:933–938

    Article  Google Scholar 

  17. Burwell R (1985) The function of bone marrow in the incorporation of a bone graft. Clin Orthop Relat Res 200:125–141

    Google Scholar 

  18. Petit-Zeman S (2001) Regenerative medicine. Nat Biotechnol 19:201–206

    Article  Google Scholar 

  19. Lam CXF et al (2002) Scaffold development using 3D printing with a starch-based polymer. Mater Sci Eng C 20:49–56

    Article  Google Scholar 

  20. Pilliar R et al (2001) Porous calcium polyphosphate scaffolds for bone substitute applications – in vitro characterization. Biomaterials 22:963–972

    Article  Google Scholar 

  21. Furth ME, Atala A, Van Dyke ME (2007) Smart biomaterials design for tissue engineering and regenerative medicine. Biomaterials 28:5068–5073

    Article  Google Scholar 

  22. Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920–6

    Article  Google Scholar 

  23. Cancedda R et al (2003) Tissue engineering and cell therapy of cartilage and bone. Matrix Biol 22:81–91

    Article  Google Scholar 

  24. Stevens L (1966) The biology of teratomas. Adv Morphog 6:1–31

    Article  Google Scholar 

  25. Pierce GB (1967) Teratocarcinoma: model for a developmental concept of cancer. Curr Top Dev Biol 2:223–246

    Article  Google Scholar 

  26. Thomas ED (2000) Landmarks in the development of hematopoietic cell transplantation. World J Surg 24:815–818

    Article  Google Scholar 

  27. Pittenger MF et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  Google Scholar 

  28. Halme DG, Kessler DA (2006) FDA regulation of stem-cell–based therapies. N Engl J Med 355:1730–1735

    Article  Google Scholar 

  29. Harrison W (1962) The total cellularity of the bone marrow in man. J Clin Pathol 15:254–259

    Article  Google Scholar 

  30. Whitfield JF (2003) How to grow bone to treat osteoporosis and mend fractures. Curr Rheumatol Rep 5:45–56

    Article  Google Scholar 

  31. Mohan S, Baylink DJ (1991) Bone growth factors. Clin Orthop Relat Res 263:30–48

    Google Scholar 

  32. Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9:641–650

    Article  Google Scholar 

  33. Augello A et al (2007) Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Arthritis Rheum 56:1175–1186

    Article  Google Scholar 

  34. Maitra B et al (2004) Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation. Bone Marrow Transplant 33:597–604

    Article  Google Scholar 

  35. Burg KJ, Porter S, Kellam JF (2000) Biomaterial developments for bone tissue engineering. Biomaterials 21:2347–2359

    Article  Google Scholar 

  36. Arpornmaeklong P et al (2004) Influence of platelet-rich plasma (PRP) on osteogenic differentiation of rat bone marrow stromal cells. An in vitro study. Int J Oral Maxillofac Surg 33:60–70

    Article  Google Scholar 

  37. Ripamonti U, Roden L (2010) Biomimetics for the induction of bone formation. Expert Rev Med Devices 7:469–479

    Article  Google Scholar 

  38. Miramond T et al (2014) Osteoinduction of biphasic calcium phosphate scaffolds in a nude mouse model. J Biomater Appl 29:595–604

    Article  Google Scholar 

  39. Habibovic P et al (2005) 3D microenvironment as essential element for osteoinduction by biomaterials. Biomaterials 26:3565–3575

    Article  Google Scholar 

  40. Assouline-Dayan Y et al (2002) Pathogenesis and natural history of osteonecrosis. In: Seminars in arthritis and rheumatism. Elsevier 32:94–124

    Google Scholar 

  41. Miramond T (2012) Développement de matrices céramiques et composites pour l’ingénierie tissulaire osseuse. In: Nantes University PhD thesis

    Google Scholar 

  42. Daculsi G, Baroth S, Sensebé L, Rosset P, Durand M, Boisteau O, Layrolle P (2011) Association cellules-matériaux pour Thérapies cellulaires Osseuses. IRBM 32:76–79

    Google Scholar 

  43. Kubo H et al (2013) Development of automated 3-dimensional tissue fabrication system tissue factory-automated cell isolation from tissue for regenerative medicine. In: Engineering in Medicine and Biology Society (EMBC), 2013 35th annual international conference of the IEEE, Osaka

    Google Scholar 

  44. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  Google Scholar 

  45. Ginn SL et al (2013) Gene therapy clinical trials worldwide to 2012–an update. J Gene Med 15:65–77

    Article  Google Scholar 

  46. Tolstoshey P (1993) Gene therapy, concepts, current trials and future directions. Annu Rev Pharmacol Toxicol 33:573–596

    Article  Google Scholar 

  47. St George J (2003) Gene therapy progress and prospects: adenoviral vectors. Gene Ther 10:1135–1141

    Article  Google Scholar 

  48. Lasic D, Templeton N (1996) Liposomes in gene therapy. Adv Drug Deliv Rev 20:221–266

    Article  Google Scholar 

  49. Niidome T, Huang L (2002) Gene therapy progress and prospects: nonviral vectors. Gene Ther 9:1647–1652

    Article  Google Scholar 

  50. Daculsi G et al (2013) Smart calcium phosphate bioceramic scaffold for bone tissue engineering. Key Eng Mater 529:19–23

    Google Scholar 

  51. Zhang Y et al (2013) Dissolution properties of different compositions of biphasic calcium phosphate bimodal porous ceramics following immersion in simulated body fluid solution. Ceram Int 39:6751–6762

    Article  Google Scholar 

  52. Daculsi G et al (2010) Developments in injectable multiphasic biomaterials. The performance of microporous biphasic calcium phosphate granules and hydrogels. J Mater Sci Mater Med 21:855–861

    Article  Google Scholar 

  53. Lan Levengood SK et al (2010) Multiscale osteointegration as a new paradigm for the design of calcium phosphate scaffolds for bone regeneration. Biomaterials 31:3552–3563

    Article  Google Scholar 

  54. Yamada S et al (1997) Osteoclastic resorption of calcium phosphate ceramics with different hydroxyapatite/β-tricalcium phosphate ratios. Biomaterials 18:1037–1041

    Article  Google Scholar 

  55. Jensen SS et al (2014) Osteoclast-like cells on deproteinized bovine bone mineral and biphasic calcium phosphate: light and transmission electron microscopical observations. Clin Oral Implants Res 26(8):859–64

    Google Scholar 

  56. Coathup MJ et al (2012) Effect of increased strut porosity of calcium phosphate bone graft substitute biomaterials on osteoinduction. J Biomed Mater Res A 100:1550–1555

    Article  Google Scholar 

  57. Chan O et al (2012) The effects of microporosity on osteoinduction of calcium phosphate bone graft substitute biomaterials. Acta Biomater 8:2788–2794

    Article  Google Scholar 

  58. Li X et al (2008) The effect of calcium phosphate microstructure on bone-related cells in vitro. Biomaterials 29:3306–3316

    Article  Google Scholar 

  59. Hollister SJ (2005) Porous scaffold design for tissue engineering. Nat Mater 4:518–524

    Article  Google Scholar 

  60. Sánchez-Salcedo S et al (2009) In vitro structural changes in porous HA/β-TCP scaffolds in simulated body fluid. Acta Biomater 5:2738–2751

    Article  Google Scholar 

  61. LeGeros RZ, Ben-Nissan B (2014) Introduction to synthetic and biologic apatites. In: Advances in calcium phosphate biomaterials. Springer, Springer Verlag Berlin Heidelberg, pp 1–17

    Google Scholar 

  62. Campion CR et al (2013) Microstructure and chemistry affects apatite nucleation on calcium phosphate bone graft substitutes. J Mater Sci Mater Med 24:597–610

    Article  Google Scholar 

  63. Cao W, Hench LL (1996) Bioactive materials. Ceram Int 22:493–507

    Article  Google Scholar 

  64. Vasilescu E et al (2011) Interactions of some new scaffolds with simulated body fluids. Rev Chim 62:212–215

    Google Scholar 

  65. Chai YC et al (2012) Current views on calcium phosphate osteogenicity and the translation into effective bone regeneration strategies. Acta Biomater 8:3876–3887

    Article  Google Scholar 

  66. LeGeros RZ (2002) Properties of osteoconductive biomaterials: calcium phosphates. Clin Orthop Relat Res 395:81–98

    Article  Google Scholar 

  67. Legeros RZ (1993) Biodegradation and bioresorption of calcium phosphate ceramics. Clin Mater 14:65–88

    Article  Google Scholar 

  68. Lu J et al (1998) Comparative study of tissue reactions to calcium phosphate ceramics among cancellous, cortical, and medullar bone sites in rabbits. J Biomed Mater Res 42:357–367

    Article  Google Scholar 

  69. Russell WMS, Burch RL (1959) The principles of humane experimental technique. Methuen, London, p 238

    Google Scholar 

  70. Castelhano-Carlos MJ, Baumans V (2009) The impact of light, noise, cage cleaning and in-house transport on welfare and stress of laboratory rats. Lab Anim 43:311–327

    Article  Google Scholar 

  71. Peric M et al (2014) The rational use of animal models in the evaluation of novel bone regenerative therapies. Bone 70:73–86

    Google Scholar 

  72. Hazzard DG et al (1992) Selection of an appropriate animal model to study aging processes with special emphasis on the use of rat strains. J Gerontol 47:B63–B64

    Article  Google Scholar 

  73. Auer JA et al (2007) Refining animal models in fracture research: seeking consensus in optimising both animal welfare and scientific validity for appropriate biomedical use. BMC Musculoskelet Disord 8:72

    Article  Google Scholar 

  74. Laroche MJ, Rousselet F (1997) Les animaux de laboratoires – Ethique et bonnes pratiques. Masson, Paris, p 393

    Google Scholar 

  75. Pearce AI et al (2007) Animal models for implant biomaterial research in bone: a review. Eur Cell Mater 13:1–10

    Google Scholar 

  76. Schimandle JH, Boden SD (1994) Spine update. The use of animal models to study spinal fusion. Spine 19:1998–2006

    Article  Google Scholar 

  77. Laporte S, Mottier D (2007) Le nombre de sujets nécessaire. Méd Thér 13:262–69

    Google Scholar 

  78. Reichert JC et al (2009) The challenge of establishing preclinical models for segmental bone defect research. Biomaterials 30:2149–2163

    Article  Google Scholar 

  79. Bonucci E, Ballanti P (2014) Osteoporosis – bone remodeling and animal models. Toxicol Pathol 42:957–969

    Google Scholar 

  80. Chappard D et al (2001) Texture analysis of X-ray radiographs is a more reliable descriptor of bone loss than mineral content in a rat model of localized disuse induced by the Clostridium botulinum toxin. Bone 28:72–79

    Article  Google Scholar 

  81. Jee WS, Yao W (2001) Overview: animal models of osteopenia and osteoporosis. J Musculoskelet Neuronal Interact 1:193–207

    Google Scholar 

  82. Hollinger JO, Kleinschmidt JC (1990) The critical size defect as an experimental model to test bone repair methods. J Craniofac Surg 1:60–68

    Article  Google Scholar 

  83. Schmitz JP, Hollinger JO (1986) The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res 205:299–308

    Google Scholar 

  84. Le Guehennec L et al (2005) Small-animal models for testing macroporous ceramic bone substitutes. J Biomed Mater Res B Appl Biomater 72:69–78

    Article  Google Scholar 

  85. Daculsi G et al (2003) Current state of the art of biphasic calcium phosphate bioceramics. J Mater Sci Mater Med 14:195–200

    Article  Google Scholar 

  86. Cunningham BW et al (2009) Ceramic granules enhanced with B2A peptide for lumbar interbody spine fusion: an experimental study using an instrumented model in sheep: laboratory investigation. J Neurosurg Spine 10:300–307

    Article  Google Scholar 

  87. Smucker JD et al (2008) B2A peptide on ceramic granules enhance posterolateral spinal fusion in rabbits compared with autograft. Spine 33:1324–1329

    Article  Google Scholar 

  88. Arinzeh TL et al (2005) A comparative study of biphasic calcium phosphate ceramics for human mesenchymal stem-cell-induced bone formation. Biomaterials 26:3631–3638

    Article  Google Scholar 

  89. Yuan H et al (2001) Bone formation induced by calcium phosphate ceramics in soft tissue of dogs: a comparative study between porous α-TCP and β-TCP. J Mater Sci Mater Med 12:7–13

    Article  Google Scholar 

  90. Yuan H et al (2002) A comparison of the osteoinductive potential of two calcium phosphate ceramics implanted intramuscularly in goats. J Mater Sci Mater Med 13:1271–1275

    Article  Google Scholar 

  91. Miramond T et al (2013) Osteopromotion of biphasic calcium phosphate granules in critical size defects after osteonecrosis induced by focal heating insults. IRBM 34:337–341

    Article  Google Scholar 

  92. Fan M et al (2011) Emu model of full-range femoral head osteonecrosis induced focally by an alternating freezing and heating insult. J Int Med Res 39:187–198

    Article  Google Scholar 

  93. Kim HK, Morgan-Bagley S, Kostenuik P (2006) RANKL inhibition: a novel strategy to decrease femoral head deformity after ischemic osteonecrosis. J Bone Miner Res 21:1946–1954

    Article  Google Scholar 

  94. Yamamoto T et al (1995) Corticosteroid enhances the experimental induction of osteonecrosis in rabbits with Shwartzman reaction. Clin Orthop Relat Res 316:235–243

    Google Scholar 

  95. Jegoux F et al (2009) Reconstruction of irradiated bone segmental defects with a biomaterial associating MBCP+®, microstructured collagen membrane and total bone marrow grafting: an experimental study in rabbits. J Biomed Mater Res A 91:1160–1169

    Article  Google Scholar 

  96. Nakamura T (1996) Bioceramics in orthopaedic surgery. Bioceramics 9:31

    Google Scholar 

  97. LeGeros RZ (2008) Calcium phosphate-based osteoinductive materials. Chem Rev 108:4742–4753

    Article  Google Scholar 

  98. Rodríguez C et al (2008) Five years clinical follow up bone regeneration with CaP bioceramics. Key Eng Mater 361:1339–1342

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dental Faculty, Laboratory for Osteoarticular and Dental Tissue Engineering, INSERM U791, Nantes University, Nantes, France

    Guy Daculsi

  2. ONIRIS, National Veterinary School of Nantes, route de Gachet, 44307, cedex 03, Nantes, France

    Eric Aguado

  3. Laboratory for Osteoarticular and Dental Tissue Engineering, INSERM U791, Nantes University, Nantes, France

    Thomas Miramond

Authors
  1. Guy Daculsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric Aguado
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Miramond
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guy Daculsi .

Editor information

Editors and Affiliations

  1. University Politehnica of Bucharest, Bucharest, Romania

    Iulian Vasile Antoniac

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this entry

Cite this entry

Daculsi, G., Aguado, E., Miramond, T. (2016). Essential Requirements for Resorbable Bioceramic Development: Research, Manufacturing, and Preclinical Studies. In: Antoniac, I. (eds) Handbook of Bioceramics and Biocomposites. Springer, Cham. https://doi.org/10.1007/978-3-319-12460-5_40

Download citation

Publish with us

Policies and ethics

Search

Navigation