Irish Journal of Medical Science (1971 -)

, Volume 184, Issue 1, pp 125–133 | Cite as

On the fate of particles liberated from hydroxyapatite coatings in vivo

  • C. F. Dunne
  • J. Gibbons
  • D. P. FitzPatrick
  • K. J. Mulhall
  • K. T. Stanton
Review Article



Hydroxyapatite (HA) has been used as a coating for orthopaedic implants for over 30 years to help promote the fixation of orthopaedic implants into the surrounding bone. However, concerns exist about the fate of the hydroxyapatite coating and hydroxyapatite particles in vivo, especially in the wake of recent concerns about particulates from metal-on-metal bearings.


Here, we assess the mechanisms of particle detachment from coated orthopaedic devices as well as the safety and performance concerns and biomedical implications arising from the liberation of the particles by review of the literature.


The mechanisms that can result in the detachment of the HA coating from the implant can be mechanical or biochemical, or both. Mechanical mechanisms include implant insertion, abrasion, fatigue and micro-motion. Biochemical mechanisms that contribute to the liberation of HA particles include dissolution into extra-cellular fluid, cell-mediated processes and crystallisation of amorphous phases. The form the particles take once liberated is influenced by a number of factors such as coating method, the raw powder morphology, processing parameters, coating thickness and coating structure.


This review summarises and discusses each of these factors and concludes that HA is a safe biomimetic material to use as a coating and does not cause any problems in particulate form if liberated as debris from an orthopaedic implant.


Hydroxyapatite Total joint replacement Coatings Plasma 



The authors wish to thank the Programme for Research in Third Level Institutions (PRTLI) for part funding of the work and Dr. Kevin Roche for providing images of the nanoparticles of HA.

Conflict of interest



  1. 1.
    Park JB, Lakes RS (2007) Biomaterials: an introduction. Springer, New YorkGoogle Scholar
  2. 2.
    Hench L, Ethridge E (1982) Biomaterials: an interfacial approachGoogle Scholar
  3. 3.
    Frosch KH, Sondergeld I, Dresing K et al (2003) Autologous osteoblasts enhance osseointegration of porous titanium implants. J Orthop Res 21:213–223CrossRefPubMedGoogle Scholar
  4. 4.
    Albrektsson T, Johansson C (2001) Osteoinduction, osteoconduction and osseointegration. Eur Spine J 10:96–101CrossRefGoogle Scholar
  5. 5.
    Blokhuis TJ, Arts JJ (2011) Bioactive and osteoinductive bone graft substitutes: definitions, facts and myths. Injury 42:26–29CrossRefGoogle Scholar
  6. 6.
    Branemark PI (1959) Vital microscopy of bone marrow in rabbit. Scand J Clin Lab Investig 11:1–82CrossRefGoogle Scholar
  7. 7.
    Branemark PI (1983) Osseointegration and its experimental studies. J Prosthet Dent 50:399–410CrossRefPubMedGoogle Scholar
  8. 8.
    Le Guehennec L, Soueidan A, Layrolle P, Amouriq Y (2007) Surface treatments of titanium dental implants for rapid osseointegration. Dent Mater 23:844–854CrossRefPubMedGoogle Scholar
  9. 9.
    Narayan R (2009) Biomedical MaterialsGoogle Scholar
  10. 10.
    Tofail SAM, Haverty D, Stanton KT, McMonagle JB (2005) Structural order and dielectric behaviour of hydroxyapatite. Ferroelectrics 319:117–123CrossRefGoogle Scholar
  11. 11.
    Haverty D, Tofail S, Stanton K, McMonagle J (2005) Structure and stability of hydroxyapatite: density functional calculation and Rietveld analysis. Phys Rev B 71:311–318CrossRefGoogle Scholar
  12. 12.
    Jinno T, Davy DT, Goldberg VM (2002) Comparison of hydroxyapatite and hydroxyapatite tricalcium-phosphate coatings. J Arthroplasty 17:902–909CrossRefPubMedGoogle Scholar
  13. 13.
    Martini FH (1998) Fundamental Anatomy and Physiology. Pearson Benjamin Cummings, San FranciscoGoogle Scholar
  14. 14.
    Ogose A, Hotta T, Kawashima H et al (2005) Comparison of hydroxyapatite and beta tricalcium phosphate as bone substitutes after excision of bone tumors. J Biomed Mater Res Part B Appl Biomater 72:94–101CrossRefPubMedGoogle Scholar
  15. 15.
    Arts JJC, Schreurs BW, Buma P, Verdonschot N (2005) Cemented cup stability during lever-out testing after acetabular bone impaction grafting with bone graft substitutes mixes containing morselized cancellous bone and tricalcium phosphate-hydroxyapatite granules. Proc Inst Mech Eng Part H J Eng Med 219:257–263CrossRefGoogle Scholar
  16. 16.
    Phipps K, Pegrum J, Smith N, Blunn G (2006) Mechanical testing of apapore as a bone graft extender. J Bone Joint Surg Br 88:373Google Scholar
  17. 17.
    Cunniffe GM, O’Brien FJ, Partap S et al (2010) The synthesis and characterization of nanophase hydroxyapatite using a novel dispersant-aided precipitation method. J Biomed Mater Res Part 95:1142–1149CrossRefGoogle Scholar
  18. 18.
    Cunniffe GM, Dickson GR, Partap S et al (2010) Development and characterisation of a collagen nano-hydroxyapatite composite scaffold for bone tissue engineering. J Mater Sci Mater Med 21:2293–2298CrossRefPubMedGoogle Scholar
  19. 19.
    Zhu SH, Huang BY, Zhou KC et al (2004) Hydroxyapatite nanoparticles as a novel gene carrier. J Nanoparticle Res 6:307–311CrossRefGoogle Scholar
  20. 20.
    Dasgupta S, Bandyopadhyay A, Bose S (2009) Reverse micelle-mediated synthesis of calcium phosphate nanocarriers for controlled release of bovine serum albumin. Acta Biomater 5:3112–3121CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Palazzo B, Iafisco M, Laforgia M et al (2007) Biomimetic hydroxyapatite–drug nanocrystals as potential bone substitutes with antitumor drug delivery properties. Adv Funct Mater 17:2180–2188CrossRefGoogle Scholar
  22. 22.
    Epinette J-A, Manley MT (eds) (2003) Fifteen years of clinical experience with hydroxyapatite coatings in joint arthroplasty. Springer, ParisGoogle Scholar
  23. 23.
    Dowson D, Taylor CM, Godet M (eds) (1990) Mechanics of coatings: Proceedings of the 16th Leeds-Lyon symposium on tribology, Lyon, France, 5–8 September 1989. North-Holland Publishing Company, AmsterdamGoogle Scholar
  24. 24.
    Bauer TW, Takikawa S (2004) Histology and Fate of Bioactive Coatings. In: Epinette J-A, Manley MT (eds) Fifteen years of clinical experience with hydoxyapatite coatings in joint arthroplasty. Springer, Paris, pp 67–74CrossRefGoogle Scholar
  25. 25.
    Overgaard S, Soballe K, Lind M, Bunger C (1997) Resorption of hydroxyapatite and fluorapatite coatings in man: an experimental study in trabecular bone. J Bone Joint Surg Br 79:654–659CrossRefPubMedGoogle Scholar
  26. 26.
    Tomino A, Oosterblos K, Rahmy A, Therin M (2004) What is the function and fate of HA coating in cementless HA-coated hip prostheses? In: Epinette J-A, Manley MT (eds) Fifteen years of clinical experience with hydoxyapatite coatings in joint arthroplasty. Springer, Paris, pp 75–86CrossRefGoogle Scholar
  27. 27.
    Bauer TW, Geesink RCT, Zimmerman R, MJ T (1991) Hydroxyapatite-coated femoral stems. Histological analysis of components retrieved at autopsy. J Bone Joint Surg 73:1439–1452PubMedGoogle Scholar
  28. 28.
    Ogiso M, Yamashita Y, Matsumoto T (1998) Microstructural changes in bone of HA-coated implants. J Biomed Mater Res 39:23–31CrossRefPubMedGoogle Scholar
  29. 29.
    Dunne CF, Twomey B, O’Neill L, Stanton KT (2014) Co-blasting of titanium surfaces with an abrasive and hydroxyapatite to produce bioactive coatings: substrate and coating characterisation. J Biomater Appl 28:767–778CrossRefPubMedGoogle Scholar
  30. 30.
    Serekian P (2004) 1: Hydroxyapatite: from plasma spray to electrical deposition. In: Epinette J-A, Manley MT (eds) Fifteen years of clinical experience with hydoxyapatite coatings in joint arthroplasty. Springer, Paris, pp 29–33CrossRefGoogle Scholar
  31. 31.
    Overgaard S, Soballe K, Josephsen K et al (1996) Role of different loading conditions on resorption of hydroxyapatite coating evaluated by histomorphometric and stereological methods. J Orthop Res 14:888–894CrossRefPubMedGoogle Scholar
  32. 32.
    Trisi P, Perfetti G, Baldoni E et al (2009) Implant micromotion is related to peak insertion torque and bone density. Clin Oral Implant Res 20:467–471CrossRefGoogle Scholar
  33. 33.
    Goltzman D (2002) Discoveries, drugs and skeletal disorders. Nat Rev Drug Discov 1:784–796CrossRefPubMedGoogle Scholar
  34. 34.
    Boyce BF, Rosenberg E, de Papp AE, Duong LT (2012) The osteoclast, bone remodelling and treatment of metabolic bone disease. Eur J Clin Investig 42:1332–1341CrossRefGoogle Scholar
  35. 35.
    Martin TJ, Sims NA (2005) Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med 11:76–81CrossRefPubMedGoogle Scholar
  36. 36.
    Rahbek O, Overgaard S, Lind M et al (2001) Sealing effect of hydroxyapatite coating on peri-implant migration of particles. An experimental study in dogs. J Bone Joint Surg Br 83:441–447CrossRefPubMedGoogle Scholar
  37. 37.
    Tsui YC, Doyle C, Clyne TW (1998) Plasma sprayed hydroxyapatite coatings on titanium substrates Part 2: optimisation of coating properties. Biomaterials 19:2031–2044CrossRefPubMedGoogle Scholar
  38. 38.
    Li H, Khor KA, Cheang P (2002) Titanium dioxide reinforced hydroxyapatite coatings deposited by high velocity oxy-fuel (HVOF) spray. Biomaterials 23:85–91CrossRefPubMedGoogle Scholar
  39. 39.
    Zhitomirsky I, Gal-Or L (1997) Electrophoretic deposition of hydroxyapatite. J Mater Sci Mater Med 8:213–219CrossRefPubMedGoogle Scholar
  40. 40.
    Garcia-Sanz FJ, Mayor MB, Arias JL et al (1997) Hydroxyapatite coatings: a comparative study between plasma-spray and pulsed laser deposition techniques. J Mater Sci Mater Med 8:861–865CrossRefPubMedGoogle Scholar
  41. 41.
    Kweh SWK, Khor KA, Cheang P (2000) Plasma-sprayed hydroxyapatite (HA) coatings with flame-spheroidized feedstock: microstructure and mechanical properties. Biomaterials 21:1223–1234CrossRefPubMedGoogle Scholar
  42. 42.
    Gross KA, Ray N, Rokkum M (2002) The contribution of coating microstructure to degradation and particle release in hydroxyapatite coated prostheses. J Biomed Mater Res 63:106–114CrossRefPubMedGoogle Scholar
  43. 43.
    Klinkov SV, Kosarev VF, Rein M (2005) Cold spray deposition: significance of particle impact phenomena. Aerosp Sci Technol 9:582–591CrossRefGoogle Scholar
  44. 44.
    Bloebaum RD, Beeks D, Dorr LD et al (1994) Complications with hydroxyapatite particulate separation in total hip arthroplasty. Clin Orthop Relat Res 298:19–26PubMedGoogle Scholar
  45. 45.
    Bloebaum RD, Lundeen GA, Bachus KN et al (1998) Dissolution of particulate hydroxyapatite in a macrophage organelle model. J Biomed Mater Res 40:104–114CrossRefPubMedGoogle Scholar
  46. 46.
    Ratner BD, Hoffman AS, Schoen FJ, Lemons JE (2004) Biomaterial science: an introduction to materials in medicine. Elsevier, AmsterdamGoogle Scholar
  47. 47.
    Bragdon CR, O’Connor DO, Lowenstein JD et al (1996) The importance of multidirectional motion on the wear of polyethylene. Proc Inst Mech Eng Part H J Eng Med 210:157–165CrossRefGoogle Scholar
  48. 48.
    Mirghany M, Jin ZM (2004) Prediction of scratch resistance of cobalt chromium alloy bearing surface, articulating against ultra-high molecular weight polyethylene, due to third-body wear particles. Proc Inst Mech Eng Part H J Eng Med 218:41–50CrossRefGoogle Scholar
  49. 49.
    Morscher EW, Hefti A, Aebi U (1998) Severe osteolysis after third-body wear due to hydroxyapatite particles from acetabular cup coating. J Bone Joint Surg Br 80:267–272CrossRefPubMedGoogle Scholar
  50. 50.
    Shanbhag AS, Jacobs JJ, Glant TT et al (1994) Composition and morphology of wear debris in failed uncemented total hip replacement. J Bone Joint Surg Br 76:60–67PubMedGoogle Scholar
  51. 51.
    Bauer TW, Taylor SK, Jiang M, Medendorp SV (1994) An indirect comparison of third-body wear in retrieved hydroxyapatite-coated, porous, and cemented femoral components. Clin Orthop Relat Res 298:11–18PubMedGoogle Scholar
  52. 52.
    Vidalain JP (2004) Corail Stem long term results based upon the 15-year arto-group experience. In: Epinette J-A, Manley MT (eds) Fifteen years of clinical experience with hydoxyapatite coatings in joint arthroplasty. Springer, Paris, pp 217–224CrossRefGoogle Scholar
  53. 53.
    Sun J-S, Liu H-C, Hong-Shong Chang W et al (1998) Influence of hydroxyapatite particle size on bone cell activities: an in vitro study. J Biomed Mater Res 39:390–397CrossRefPubMedGoogle Scholar
  54. 54.
    Evans EJ (1991) Toxicity of hydroxyapatite in vitro: the effect of particle size. Biomaterials 12:574–576CrossRefPubMedGoogle Scholar
  55. 55.
    Evans EJ, Clarke-Smith EMH (1991) Studies on the mechanism of cell damage by finely ground hydroxyapatite particles in vitro. Clin Mater 7:241–245CrossRefGoogle Scholar
  56. 56.
    Evans EJ (1994) Cell damage in vitro following direct contact with fine particles of titanium, titanium alloy and cobalt-chrome-molybdenum alloy. Biomaterials 15:713–717CrossRefPubMedGoogle Scholar
  57. 57.
    Sun J-S, Tsuang Y-H, Chang WH-S et al (1997) Effect of hydroxyapatite particle size on myoblasts and fibroblasts. Biomaterials 18:683–690CrossRefPubMedGoogle Scholar
  58. 58.
    Nordsletten L, Høgåsen AKM, Konttinen Y et al (1996) Human monocytes stimulation by particles of hydroxyapatite, silicon carbide and diamond: in vitro studies of new prosthesis coatings. Biomaterials 17:1521–1527CrossRefPubMedGoogle Scholar
  59. 59.
    Sun J-S, Lin F-H, Hung T-Y et al (1999) The influence of hydroxyapatite particles on osteoclast cell activities. J Biomed Mater Res 45:311–321CrossRefPubMedGoogle Scholar
  60. 60.
    Ninomiya JT, Struve JA, Stelloh CT et al (2001) Effects of hydroxyapatite participate debris on the production of cytokines and proteases in human fibroblasts. J Orthop Res 19:621–628CrossRefPubMedGoogle Scholar
  61. 61.
    Wang J-S, Goodman S, Aspenberg P (1994) Bone formation in the presence of phagocytosable hydroxyapatite particles. Clin Orthop Relat Res 304:272–279PubMedGoogle Scholar
  62. 62.
    Rahbek O, Kold S, Bendix K et al (2005) No effect of hydroxyapatite particles in phagocytosable sizes on implant fixation: an experimental study in dogs. J Biomed Mater Res Part 73:150–157CrossRefGoogle Scholar
  63. 63.
    Urban RM, Jacobs JJ, Tomlinson MJ et al (2000) Dissemination of Wear Particles to the liver, spleen, and abdominal lymph nodes of patients with hip or knee replacement. J Bone Joint Surg 82:457–476CrossRefPubMedGoogle Scholar
  64. 64.
    Gill HS, Grammatopoulos G, Adshead S et al (2012) Molecular and immune toxicity of CoCr nanoparticles in MoM hip arthroplasty. Trends Mol Med 18:145–155CrossRefPubMedGoogle Scholar
  65. 65.
    Hatton A, Nevelos JE, Nevelos AA et al (2002) Alumina–alumina artificial hip joints. Part I: a histological analysis and characterisation of wear debris by laser capture microdissection of tissues retrieved at revision. Biomaterials 23:3429–3440CrossRefPubMedGoogle Scholar
  66. 66.
    Germain MA, Hatton A, Williams S et al (2003) Comparison of the cytotoxicity of clinically relevant cobalt–chromium and alumina ceramic wear particles in vitro. Biomaterials 24:469–479CrossRefPubMedGoogle Scholar
  67. 67.
    Tipper JL, Firkins PJ, Besong AA et al (2001) Characterisation of wear debris from UHMWPE on zirconia ceramic, metal-on-metal and alumina ceramic-on-ceramic hip prostheses generated in a physiological anatomical hip joint simulator. Wear 250:120–128CrossRefGoogle Scholar
  68. 68.
    Jin ZM, Stone M, Ingham E, Fisher J (2006) (v) Biotribology. Curr Orthop 20:32–40CrossRefGoogle Scholar
  69. 69.
    Roche KJ, Stanton KT (2014) Measurement of fluoride substitution in precipitated fluorhydroxyapatite nanoparticles. J Fluor Chem 161:102–109CrossRefGoogle Scholar
  70. 70.
    Graves S, Davidson D, de Steiger R, Tomkins A (2011) Austrailian Orthopaedic Association National Joint Replacement Registry-Annual Report 2011Google Scholar
  71. 71.
    Hamadouche M, Witvoet J, Porcher R et al (2001) Hydroxyapatite-coated versus grit-blasted femoral stems A Prospective randomised study using EBRA-FCA. J Bone Joint Surg Br 83:979–987CrossRefPubMedGoogle Scholar
  72. 72.
    McNally SA, Shepperd JA, Mann CV, Walczak JP (2000) The results at nine to twelve years of the use of a hydroxyapatite-coated femoral stem. J Bone Joint Surg Br 82:378–382CrossRefPubMedGoogle Scholar

Copyright information

© Royal Academy of Medicine in Ireland 2015

Authors and Affiliations

  • C. F. Dunne
    • 1
  • J. Gibbons
    • 2
  • D. P. FitzPatrick
    • 1
  • K. J. Mulhall
    • 3
  • K. T. Stanton
    • 1
  1. 1.UCD School of Mechanical and Materials EngineeringUniversity College DublinDublin 4Ireland
  2. 2.Department of TraumaAdelaide and Meath Hospital, Incorporating the National Children’s HospitalDublin 24Ireland
  3. 3.Department of Orthopaedic SurgeryMater Misericordiae University HospitalDublin 7Ireland

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