Skip to main content
SpringerLink
Log in

Calcium Phosphate Biomaterials for Bone Tissue Engineering: Properties and Relevance in Bone Repair

  • Chapter
  • First Online:
Racing for the Surface

Abstract

Bone defects are common and are associated with a significant burden of disease threatening the health of many people around the globe. Since the last decade, data obtained from case studies have demonstrated that 20% of patients who experience an osteoporotic hip break are unable to endure the primary year after medical treatment. Many similar cases suggest that there is a huge requirement for better treatment of unhealthy and broken bones. Human bone comprises of about 70% of calcium phosphate (CaP) mineral, therefore CaPs are possible alternative materials to fix a broken bone. CaP is broadly utilized for bone fixation because of its bioactive properties like osteoinductivity, osteoconductivity, and biodegradability. Therefore, examination of these properties and the impact of their different affecting factors are crucial for balancing CaP during the fabrication procedure to maximally fulfill required clinical prerequisites. The aim of this chapter is to highlight the systems behind the CaP-assisted bone development in the initial phase, specifically as a biocompatible bone graft substitute. In this study, the latest developments in the biological properties of CaP biomaterials, including hydroxyapatite (HA), tricalcium phosphate (TCP), and biphasic CaP (BCP), have been summarized. Moreover, recent advances on how their properties are altered by different factors are reviewed. Finally, perspectives regarding future developments of CaP materials are provided.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

References

  1. Woolf AD, Pfleger B (2003) Burden of major musculoskeletal conditions. Bull World Health Organ 81:646–656

    PubMed  PubMed Central  Google Scholar 

  2. Brooks PM (2002) Impact of osteoarthritis on individuals and society: how much disability? Social consequences and health economic implications. Curr Opin Rheumatol 14(5):573–577

    Article  PubMed  Google Scholar 

  3. Mistry AS, Mikos AG (2005) Tissue engineering strategies for bone regeneration. In: Regenerative medicine II. Springer, Berlin, pp 1–22

    Google Scholar 

  4. Burt DW, Law AS (1994) Evolution of the transforming growth factor-beta superfamily. Prog Growth Factor Res 5(1):99–118

    Article  CAS  PubMed  Google Scholar 

  5. Ross R, Raines EW, Bowen-Pope DF (1986) The biology of platelet-derived growth factor. Cell 46(2):155–169

    Article  CAS  PubMed  Google Scholar 

  6. Humbel RE (1990) Insulin-like growth factors I and II. Eur J Biochem 190(3):445–462

    Article  CAS  PubMed  Google Scholar 

  7. Opal SM, Depalo VA (2000) Anti-inflammatory cytokines. Chest 117(4):1162–1172

    Article  CAS  PubMed  Google Scholar 

  8. Springer IN et al (2004) Particulated bone grafts–effectiveness of bone cell supply. Clin Oral Implants Res 15(2):205–212

    Article  PubMed  Google Scholar 

  9. Naran S, Menard RM (2015) Bone grafting: physiology and techniques. In: Ferraro’s fundamentals of maxillofacial surgery. Springer, Berlin, pp 115–133

    Chapter  Google Scholar 

  10. Giannoudis PV, Dinopoulos H, Tsiridis E (2005) Bone substitutes: an update. Injury 36(3):S20–S27

    PubMed  Google Scholar 

  11. Radin S, Ducheyne P (1993) The effect of calcium phosphate ceramic composition and structure on in vitro behavior. II. Precipitation. J Biomed Mater Res 27(1):35–45

    Article  CAS  PubMed  Google Scholar 

  12. Nandi S et al (2010) Orthopaedic applications of bone graft & graft substitutes: a review. Indian J Med Res 132(1):15–30

    CAS  PubMed  Google Scholar 

  13. Ferna E et al (1999) Calcium phosphate bone cements for clinical applications. Part I: solution chemistry. J Mater Sci Mater Med 10(3):169–176

    Article  Google Scholar 

  14. Zeng H, Chittur KK, Lacefield WR (1999) Analysis of bovine serum albumin adsorption on calcium phosphate and titanium surfaces. Biomaterials 20(4):377–384

    Article  CAS  PubMed  Google Scholar 

  15. Zhu X et al (2010) Effect of phase composition and microstructure of calcium phosphate ceramic particles on protein adsorption. Acta Biomater 6(4):1536–1541

    Article  CAS  PubMed  Google Scholar 

  16. Boyan BD et al (1996) Role of material surfaces in regulating bone and cartilage cell response. Biomaterials 17(2):137–146

    Article  CAS  PubMed  Google Scholar 

  17. Wang C et al (2004) Phenotypic expression of bone-related genes in osteoblasts grown on calcium phosphate ceramics with different phase compositions. Biomaterials 25(13):2507–2514

    Article  CAS  PubMed  Google Scholar 

  18. Rho J-Y, Kuhn-Spearing L, Zioupos P (1998) Mechanical properties and the hierarchical structure of bone. Med Eng Phys 20(2):92–102

    Article  CAS  PubMed  Google Scholar 

  19. Gao H (2006) Application of fracture mechanics concepts to hierarchical biomechanics of bone and bone-like materials. Int J Fract 138(1-4):101

    Article  Google Scholar 

  20. Huang S et al (2014) A novel model for porous scaffold to match the mechanical anisotropy and the hierarchical structure of bone. Mater Lett 122:315–319

    Article  CAS  Google Scholar 

  21. Reznikov N, Shahar R, Weiner S (2014) Bone hierarchical structure in three dimensions. Acta Biomater 10(9):3815–3826

    Article  PubMed  Google Scholar 

  22. Lemons J (1993) Inorganic and organic composition for treatment of bone lesions. Google Patents

    Google Scholar 

  23. Szabo CM, Martin MB, Oldfield E (2002) An investigation of bone resorption and Dictyostelium discoideum growth inhibition by bisphosphonate drugs. J Med Chem 45(14):2894–2903

    Article  CAS  PubMed  Google Scholar 

  24. Inanç B, Elcin AE, Elcin YM (2007) Effect of osteogenic induction on the in vitro differentiation of human embryonic stem cells cocultured with periodontal ligament fibroblasts. Artif Organs 31(11):792–800

    Article  PubMed  CAS  Google Scholar 

  25. Xia Z et al (2006) In vitro biodegradation of three brushite calcium phosphate cements by a macrophage cell-line. Biomaterials 27(26):4557–4565

    Article  CAS  PubMed  Google Scholar 

  26. Choi K et al (1990) The elastic moduli of human subchondral, trabecular, and cortical bone tissue and the size-dependency of cortical bone modulus. J Biomech 23(11):1103–1113

    Article  CAS  PubMed  Google Scholar 

  27. Boivin G, Meunier PJ (2003) Methodological considerations in measurement of bone mineral content. Osteoporos Int 14(5):22–28

    Article  Google Scholar 

  28. Fennis J, Stoelinga P, Jansen J (2004) Mandibular reconstruction: a histological and histomorphometric study on the use of autogenous scaffolds, particulate cortico-cancellous bone grafts and platelet rich plasma in goats. Int J Oral Maxillofac Surg 33(1):48–55

    Article  CAS  PubMed  Google Scholar 

  29. Silva R et al (2005) The use of hydroxyapatite and autogenous cancellous bone grafts to repair bone defects in rats. Int J Oral Maxillofac Surg 34(2):178–184

    Article  CAS  PubMed  Google Scholar 

  30. Moore WR, Graves SE, Bain GI (2001) Synthetic bone graft substitutes. ANZ J Surg 71(6):354–361

    Article  CAS  PubMed  Google Scholar 

  31. Finkemeier CG (2002) Bone-grafting and bone-graft substitutes. JBJS 84(3):454–464

    Article  Google Scholar 

  32. Weiner S, Wagner HD (1998) The material bone: structure-mechanical function relations. Annu Rev Mater Sci 28(1):271–298

    Article  CAS  Google Scholar 

  33. Nakase T et al (1994) Alterations in the expression of osteonectin, osteopontin and osteocalcin mRNAs during the development of skeletal tissues in vivo. Bone Miner 26(2):109–122

    Article  CAS  PubMed  Google Scholar 

  34. Florencio-Silva R et al (2015) Biology of bone tissue: structure, function, and factors that influence bone cells. Biomed Res Int 2015:421746

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Ferro F et al (2010) Biochemical and biophysical analyses of tissue-engineered bone obtained from three-dimensional culture of a subset of bone marrow mesenchymal stem cells. Tissue Eng Part A 16(12):3657–3667

    Article  CAS  PubMed  Google Scholar 

  36. Klein M et al (2009) Pore characteristics of bone substitute materials assessed by microcomputed tomography. Clin Oral Implants Res 20(1):67–74

    Article  CAS  PubMed  Google Scholar 

  37. Karageorgiou V, Kaplan D (2005) Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 26(27):5474–5491

    Article  CAS  PubMed  Google Scholar 

  38. Hannink G, Arts JC (2011) Bioresorbability, porosity and mechanical strength of bone substitutes: what is optimal for bone regeneration? Injury 42:S22–S25

    Article  PubMed  Google Scholar 

  39. Vallet-Regi M, González-Calbet JM (2004) Calcium phosphates as substitution of bone tissues. Prog Solid State Chem 32(1-2):1–31

    Article  CAS  Google Scholar 

  40. Wopenka B, Pasteris JD (2005) A mineralogical perspective on the apatite in bone. Mater Sci Eng C 25(2):131–143

    Article  CAS  Google Scholar 

  41. Legeros RZ (1981) Apatites in biological systems. Progr Crystal Growth Character 4(1-2):1–45

    Article  CAS  Google Scholar 

  42. Dorozhkin SV, Epple M (2002) Biological and medical significance of calcium phosphates. Angew Chem Int Ed 41(17):3130–3146

    Article  CAS  Google Scholar 

  43. Sun F, Zhou H, Lee J (2011) Various preparation methods of highly porous hydroxyapatite/polymer nanoscale biocomposites for bone regeneration. Acta Biomater 7(11):3813–3828

    Article  CAS  PubMed  Google Scholar 

  44. Ferreira A, Oliveira C, Rocha F (2003) The different phases in the precipitation of dicalcium phosphate dihydrate. J Cryst Growth 252(4):599–611

    Article  CAS  Google Scholar 

  45. Tang R et al (2003) Constant composition dissolution of mixed phases: II. Selective dissolution of calcium phosphates. J Colloid Interface Sci 260(2):379–384

    Article  CAS  PubMed  Google Scholar 

  46. Nancollas G, Tomazic B (1974) Growth of calcium phosphate on hydroxyapatite crystals. Effect of supersaturation and ionic medium. J Phys Chem 78(22):2218–2225

    Article  CAS  Google Scholar 

  47. Zhao J et al (2014) Rietveld refinement of hydroxyapatite, tricalcium phosphate and biphasic materials prepared by solution combustion method. Ceram Int 40(2):3379–3388

    Article  CAS  Google Scholar 

  48. Carrodeguas RG, De Aza S (2011) α-Tricalcium phosphate: synthesis, properties and biomedical applications. Acta Biomater 7(10):3536–3546

    Article  CAS  PubMed  Google Scholar 

  49. Kamitakahara M, Ohtsuki C, Miyazaki T (2008) Behavior of ceramic biomaterials derived from tricalcium phosphate in physiological condition. J Biomater Appl 23(3):197–212

    Article  CAS  PubMed  Google Scholar 

  50. Cicek G et al (2011) Alpha-tricalcium phosphate (α-TCP): solid state synthesis from different calcium precursors and the hydraulic reactivity. J Mater Sci Mater Med 22(4):809–817

    Article  CAS  PubMed  Google Scholar 

  51. Nilsson M et al (2002) Characterization of a novel calcium phosphate/sulphate bone cement. J Biomed Mater Res 61(4):600–607

    Article  CAS  PubMed  Google Scholar 

  52. LeGeros RZ (2008) Calcium phosphate-based osteoinductive materials. Chem Rev 108(11):4742–4753

    Article  PubMed  CAS  Google Scholar 

  53. Yamada S et al (1997) Osteoclastic resorption of biphasic calcium phosphate ceramic in vitro. J Biomed Mater Res 37(3):346–352

    Article  CAS  PubMed  Google Scholar 

  54. Berry E (1967) The structure and composition of some calcium-deficient apatites. J Inorg Nucl Chem 29(2):317–327

    Article  CAS  Google Scholar 

  55. Hutchens SA et al (2006) Biomimetic synthesis of calcium-deficient hydroxyapatite in a natural hydrogel. Biomaterials 27(26):4661–4670

    Article  CAS  PubMed  Google Scholar 

  56. Ravi ND, Balu R, Sampath Kumar T (2012) Strontium-substituted calcium deficient hydroxyapatite nanoparticles: synthesis, characterization, and antibacterial properties. J Am Ceram Soc 95(9):2700–2708

    Article  CAS  Google Scholar 

  57. Klein CP et al (1990) Studies of the solubility of different calcium phosphate ceramic particles in vitro. Biomaterials 11(7):509–512

    Article  CAS  PubMed  Google Scholar 

  58. Yamada S et al (1997) Osteoclastic resorption of calcium phosphate ceramics with different hydroxyapatite/β-tricalcium phosphate ratios. Biomaterials 18(15):1037–1041

    Article  CAS  PubMed  Google Scholar 

  59. Klein C et al (1983) Biodegradation behavior of various calcium phosphate materials in bone tissue. J Biomed Mater Res 17(5):769–784

    Article  CAS  PubMed  Google Scholar 

  60. Groot KD (1988) Effect of porosity and physicochemical properties on the stability, resorption, and strength of calcium phosphate ceramics. Ann N Y Acad Sci 523(1):227–233

    Article  PubMed  Google Scholar 

  61. de Groot K (2018) Ceramics of calcium phosphates: preparation and properties. In: Bioceramics calcium phosphate. CRC, Boca Raton, FL, pp 99–114

    Chapter  Google Scholar 

  62. Sun L et al (2010) Preparation and properties of nanoparticles of calcium phosphates with various Ca/P ratios. J Res Natl Inst Standards Technol 115(4):243

    Article  CAS  Google Scholar 

  63. ŚAlósarczyk A et al (1996) Calcium phosphate materials prepared from precipitates with various calcium: phosphorus molar ratios. J Am Ceram Soc 79(10):2539–2544

    Article  Google Scholar 

  64. Eyckmans J et al (2010) A clinically relevant model of osteoinduction: a process requiring calcium phosphate and BMP/Wnt signalling. J Cell Mol Med 14(6b):1845–1856

    Article  CAS  PubMed  Google Scholar 

  65. Samavedi S, Whittington AR, Goldstein AS (2013) Calcium phosphate ceramics in bone tissue engineering: a review of properties and their influence on cell behavior. Acta Biomater 9(9):8037–8045

    Article  CAS  PubMed  Google Scholar 

  66. Zayzafoon M (2006) Calcium/calmodulin signalling controls osteoblast growth and differentiation. J Cell Biochem 97(1):56–70

    Article  CAS  PubMed  Google Scholar 

  67. Barradas AM et al (2012) A calcium-induced signalling cascade leading to osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells. Biomaterials 33(11):3205–3215

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  69. Lu J, Yu H, Chen C (2018) Biological properties of calcium phosphate biomaterials for bone repair: a review. RSC Adv 8(4):2015–2033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Li S et al (2003) Macroporous biphasic calcium phosphate scaffold with high permeability/porosity ratio. Tissue Eng 9(3):535–548

    Article  CAS  PubMed  Google Scholar 

  71. Kitsugi T et al (1993) Four calcium phosphate ceramics as bone substitutes for non-weight-bearing. Biomaterials 14(3):216–224

    Article  CAS  PubMed  Google Scholar 

  72. Ambard AJ, Mueninghoff L (2006) Calcium phosphate cement: review of mechanical and biological properties. J Prosthodont 15(5):321–328

    Article  PubMed  Google Scholar 

  73. Sheikh Z et al (2015) Mechanisms of in vivo degradation and resorption of calcium phosphate based biomaterials. Materials 8(11):7913–7925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Benahmed M et al (1996) Biodegradation of synthetic biphasic calcium phosphate by human monocytes in vitro: a morphological study. Biomaterials 17(22):2173–2178

    Article  CAS  PubMed  Google Scholar 

  75. Aparicio JL et al (2016) Effect of physicochemical properties of a cement based on silicocarnotite/calcium silicate on in vitro cell adhesion and in vivo cement degradation. Biomed Mater 11(4):045005

    Article  PubMed  CAS  Google Scholar 

  76. Heymann D, Pradal G, Benahmed M (1999) Cellular mechanisms of calcium phosphate ceramic degradation. Histol Histopathol 14(3):871–877

    CAS  PubMed  Google Scholar 

  77. Sun H et al (2006) Proliferation and osteoblastic differentiation of human bone marrow-derived stromal cells on akermanite-bioactive ceramics. Biomaterials 27(33):5651–5657

    Article  CAS  PubMed  Google Scholar 

  78. Wang J et al (1998) Biological evaluation of biphasic calcium phosphate ceramic vertebral laminae. Biomaterials 19(15):1387–1392

    Article  CAS  PubMed  Google Scholar 

  79. Yang X (2017) Hydroxyapatite: design with nature. In: Orthopedic biomaterials. Springer, Berlin, pp 141–165

    Chapter  Google Scholar 

  80. Venkatesan J et al (2015) Alginate composites for bone tissue engineering: a review. Int J Biol Macromol 72:269–281

    Article  CAS  PubMed  Google Scholar 

  81. Du C et al (2000) Formation of calcium phosphate/collagen composites through mineralization of collagen matrix. J Biomed Mater Res 50(4):518–527

    Article  CAS  PubMed  Google Scholar 

  82. Mendonça G et al (2008) Advancing dental implant surface technology–from micron-to nanotopography. Biomaterials 29(28):3822–3835

    Article  PubMed  CAS  Google Scholar 

  83. Hu Q et al (2007) Effect of crystallinity of calcium phosphate nanoparticles on adhesion, proliferation, and differentiation of bone marrow mesenchymal stem cells. J Mater Chem 17(44):4690–4698

    Article  CAS  Google Scholar 

  84. Dulgar-Tulloch A, Bizios R, Siegel R (2009) Human mesenchymal stem cell adhesion and proliferation in response to ceramic chemistry and nanoscale topography. J Biomed Mater Res A 90(2):586–594

    Article  CAS  PubMed  Google Scholar 

  85. Xu B et al (2012) RhoA/ROCK, cytoskeletal dynamics, and focal adhesion kinase are required for mechanical stretch-induced tenogenic differentiation of human mesenchymal stem cells. J Cell Physiol 227(6):2722–2729

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank the Department of Ceramic Engineering and Biotechnology and Medical Engineering (NIT Rourkela, India), Dr. Sudip Dasgupta (Department of Ceramic Engineering, NIT Rourkela) for a critical review of the manuscript and for providing valuable suggestions.

Author information

Authors and Affiliations

  1. Department of Ceramic Engineering, NIT Rourkela, Rourkela, Odisha, India

    Kanchan Maji & Soumini Mondal

Authors
  1. Kanchan Maji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Soumini Mondal
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Orthopaedics School of Medicine, West Virginia University, Morgantown, WV, USA

    Bingyun Li

  2. AO Research Institute Davos, Davos Platz, Graubünden, Switzerland

    Thomas Fintan Moriarty

  3. Department of Chemical Engineering, Northeastern University, Boston, MA, USA

    Thomas Webster

  4. Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB, Canada

    Malcolm Xing

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Maji, K., Mondal, S. (2020). Calcium Phosphate Biomaterials for Bone Tissue Engineering: Properties and Relevance in Bone Repair. In: Li, B., Moriarty, T., Webster, T., Xing, M. (eds) Racing for the Surface. Springer, Cham. https://doi.org/10.1007/978-3-030-34471-9_20

Download citation

Publish with us

Policies and ethics

Search

Navigation