Hydroxyapatite for Biomedicine and Drug Delivery

  • Behrad Ghiasi
  • Yahya SefidbakhtEmail author
  • Maryam Rezaei
Part of the Advanced Structured Materials book series (STRUCTMAT, volume 104)


Hydroxyapatite (HA) is a member of the calcium phosphates family (Table 1) and like the other ones is known as a bioceramic with specific advantages raise from chemical similarity to the mammalian inorganic structure. In comparison to other CaPs, HA has highest thermodynamic stability and solubility (after Fluorapatite) in physiological conditions.


  1. Agarwalla, A., Puzzitiello, R., Garcia, G.H., Forsythe, B.: Application of a beta-tricalcium phosphate graft to minimize bony defect in bone–patella tendon–bone anterior cruciate ligament reconstruction. Arthrosc. Techn. 7, e725 (2018)CrossRefGoogle Scholar
  2. Ahn, E.S., Gleason, N.J., Nakahira, A., Ying, J.Y.: Nanostructure processing of hydroxyapatite-based bioceramics. Nano Lett. 1(3), 149–153 (2001)CrossRefGoogle Scholar
  3. Akram, M., Ahmed, R., Shakir, I., Ibrahim, W.A.W., Hussain, R.: Extracting hydroxyapatite and its precursors from natural resources. J. Mater. Sci. 49(4), 1461–1475 (2014)CrossRefGoogle Scholar
  4. Almeida, A.L., Martins, J.B.L., Taft, C.A., Longo, E., Andres, J., Lie, S.K.: A PM3 theoretical study of the adsorption and dissociation of water on MgO surfaces. J. Mol. Struct. (Thoechem.) 426(1–3), 199–205 (1998)CrossRefGoogle Scholar
  5. Antony, G.J.M., Aruna, S., Raja, S.: Enhanced mechanical properties of acrylate based shape memory polymer using grafted hydroxyapatite. J. Polym. Res. 25(5), 120 (2018)CrossRefGoogle Scholar
  6. Awwad, N., Alshahrani, A., Saleh, K., Hamdy, M.: A novel method to improve the anticancer activity of natural-based hydroxyapatite against the liver cancer cell line HepG2 using mesoporous magnesia as a micro-carrier. Molecules 22(12), 1947 (2017)CrossRefGoogle Scholar
  7. Azarpazhooh, A., Limeback, H.: Clinical efficacy of casein derivatives: a systematic review of the literature. J. Am. Dent. Assoc. 139(7), 915–924 (2008)CrossRefGoogle Scholar
  8. Bamrungsap, S., Zhao, Z., Chen, T., Wang, L., Li, C., Fu, T., Tan, W.: Nanotechnology in therapeutics: a focus on nanoparticles as a drug delivery system. Nanomedicine 7(8), 1253–1271 (2012)CrossRefGoogle Scholar
  9. Bansal, M., Mittal, N., Yadav, S.K., Khan, G., Gupta, P., Mishra, B., Nath, G.: Periodontal thermoresponsive, mucoadhesive dual antimicrobial loaded in-situ gel for the treatment of periodontal disease: preparation, in-vitro characterization and antimicrobial study. J. Oral Biol. Craniofacial Res. 8(2), 126–133 (2018)CrossRefGoogle Scholar
  10. Barakat, N.A.M., Khil, M.S., Omran, A.M., Sheikh, F.A., Kim, H.Y.: Extraction of pure natural hydroxyapatite from the bovine bones bio waste by three different methods. J. Mater. Process. Technol. 209(7), 3408–3415 (2009)CrossRefGoogle Scholar
  11. Batchelar, D.L., Davidson, M.T.M., Dabrowski, W., Cunningham, I.A.: Bone-composition imaging using coherent-scatter computed tomography: assessing bone health beyond bone mineral density. Med. Phys. 33(4), 904–915 (2006)CrossRefGoogle Scholar
  12. Besinis, A., De Peralta, T., Tredwin, C.J., Handy, R.D.: Review of nanomaterials in dentistry: interactions with the oral microenvironment, clinical applications, hazards, and benefits. ACS Nano 9(3), 2255–2289 (2015)CrossRefGoogle Scholar
  13. Best, S., Porter, A., Thian, E., Huang, J.: Bioceramics: past, present and for the future. J. Eur. Ceram. Soc. 28(7), 1319–1327 (2008)CrossRefGoogle Scholar
  14. Bian, S.-W., Baltrusaitis, J., Galhotra, P., Grassian, V.H.: A template-free, thermal decomposition method to synthesize mesoporous MgO with a nanocrystalline framework and its application in carbon dioxide adsorption. J. Mater. Chem. 20(39), 8705 (2010)CrossRefGoogle Scholar
  15. Bianco, A., Cacciotti, I., Lombardi, M., Montanaro, L.: Si-substituted hydroxyapatite nanopowders: synthesis, thermal stability and sinterability. Mater. Res. Bull. 44(2), 345–354 (2009)CrossRefGoogle Scholar
  16. Bose, S., Banerjee, A., Dasgupta, S., Bandyopadhyay, A.: Synthesis, processing, mechanical, and biological property characterization of hydroxyapatite whisker-reinforced hydroxyapatite composites. J. Am. Ceram. Soc. 92(2), 323–330 (2009)CrossRefGoogle Scholar
  17. Bose, S., Dasgupta, S., Tarafder, S., Bandyopadhyay, A.: Microwave-processed nanocrystalline hydroxyapatite: simultaneous enhancement of mechanical and biological properties. Acta Biomater. 6(9), 3782–3790 (2010)CrossRefGoogle Scholar
  18. Cai, Y., Liu, Y., Yan, W., Hu, Q., Tao, J., Zhang, M., Shi, Z., Tang, R.: Role of hydroxyapatite nanoparticle size in bone cell proliferation. J. Mater. Chem. 17(36), 3780–3787 (2007)CrossRefGoogle Scholar
  19. Cai, J., Palamara, J., Manton, D., Burrow, M.: Status and progress of treatment methods for root caries in the last decade: a literature review. Aust. Dent. J. 63(1), 34–54 (2018)CrossRefGoogle Scholar
  20. Carrodeguas, R.G., De Aza, S.: α-Tricalcium phosphate: synthesis, properties and biomedical applications. Acta Biomater. 7(10), 3536–3546 (2011)CrossRefGoogle Scholar
  21. Chakraborty, R., Seesala, V.S., Sen, M., Sengupta, S., Dhara, S., Saha, P., Das, K., Das, S.: MWCNT reinforced bone like calcium phosphate—Hydroxyapatite composite coating developed through pulsed electrodeposition with varying amount of apatite phase and crystallinity to promote superior osteoconduction, cytocompatibility and corrosion protection performance compared to bare metallic implant surface. Surf. Coat. Technol. 325, 496–514 (2017)CrossRefGoogle Scholar
  22. Chan, W.C.W., Khademhosseini, A., Parak, W., Weiss, P.S.: Cancer: nanoscience and nanotechnology approaches. ACS Nano 11(5), 4375–4376 (2017)CrossRefGoogle Scholar
  23. Chen, Q., Cao, L., Wang, J., Jiang, L., Zhao, H., Yishake, M., Ma, Y., Zhou, H., Lin, H., Dong, J., Fan, Z.: Bioinspired modification of poly(L-lactic acid)/nano-sized beta-tricalcium phosphate composites with gelatin/hydroxyapatite coating for enhanced osteointegration and osteogenesis (2018). 1550-7033 (Print)Google Scholar
  24. Chen, D.Z., Tang, C.Y., Chan, K.C., Tsui, C.P., Yu, P.H.F., Leung, M.C.P., Uskokovic, P.S.: Dynamic mechanical properties and in vitro bioactivity of PHBHV/HA nanocomposite. Compos. Sci. Technol. 67(7), 1617–1626 (2007)CrossRefGoogle Scholar
  25. Chen, Y., Huang, Z., Li, X., Li, S., Zhou, Z., Zhang, Y., Feng, Q.L., Yu, B.: In vitro biocompatibility and osteoblast differentiation of an injectable Chitosan/Nano-Hydroxyapatite/Collagen scaffold. J. Nanomater. 2012, 6 (2012)Google Scholar
  26. Cui, H., Wu, X., Chen, Y., Boughton, R.I.: Synthesis and characterization of mesoporous MgO by template-free hydrothermal method. Mater. Res. Bull. 50, 307–311 (2014)CrossRefGoogle Scholar
  27. De Groot, K., Geesink, R., Klein, C., Serekian, P.: Plasma sprayed coatings of hydroxylapatite. J. Biomed. Mater. Res., Part A 21(12), 1375–1381 (1987)CrossRefGoogle Scholar
  28. Dhand, V., Rhee, K.Y., Park, S.-J.: The facile and low temperature synthesis of nanophase hydroxyapatite crystals using wet chemistry. Mater. Sci. Eng. C 36, 152–159 (2014)CrossRefGoogle Scholar
  29. Dong, Z., Li, Y., Zou, Q.: Degradation and biocompatibility of porous nano-hydroxyapatite/polyurethane composite scaffold for bone tissue engineering. Appl. Surf. Sci. 255(12), 6087–6091 (2009)CrossRefGoogle Scholar
  30. Dorozhkin, S.V.: Nanosized and nanocrystalline calcium orthophosphates. Acta Biomater. 6(3), 715–734 (2010)CrossRefGoogle Scholar
  31. Dorozhkin, S.V.: Calcium orthophosphate bioceramics. Ceram. Int. 41(10), 13913–13966 (2015)CrossRefGoogle Scholar
  32. Dorozhkin, S.V.: Self-setting Calcium Orthophosphate (CaPO4) Formulations. Developments and Applications of Calcium Phosphate Bone Cements, pp. 41–146. Springer, Singapore (2018)CrossRefGoogle Scholar
  33. Durgesh, B.H., Basavarajappa, S., Ramakrishnaiah, R., Al Kheraif, A.A., Divakar, D.D.: A review on microbiological cause of periodontal disease: disease and treatment. Rev. Med. Microbiol. 26(2), 53–58 (2015)CrossRefGoogle Scholar
  34. Elkassas, D., Arafa, A.: Remineralizing efficacy of different calcium-phosphate and fluoride based delivery vehicles on artificial caries like enamel lesions. J. Dent. 42(4), 466–474 (2014)CrossRefGoogle Scholar
  35. Elsabahy, M., Wooley, K.L.: Design of polymeric nanoparticles for biomedical delivery applications. Chem. Soc. Rev. 41(7), 2545 (2012)CrossRefGoogle Scholar
  36. Eriksson, M., Liu, Y., Hu, J., Gao, L., Nygren, M., Shen, Z.: Transparent hydroxyapatite ceramics with nanograin structure prepared by high pressure spark plasma sintering at the minimized sintering temperature. J. Eur. Ceram. Soc. 31(9), 1533–1540 (2011)CrossRefGoogle Scholar
  37. Etienne, D.: Locally delivered antimicrobials for the treatment of chronic periodontitis. Oral Dis. 9(s1), 45–50 (2003)CrossRefGoogle Scholar
  38. Faeda, R.S., Tavares, H.S., Sartori, R., Sartori, A.C., Marcantonio Jr., E.: Biological performance of chemical hydroxyapatite coating associated with implant surface modification by laser beam: biomechanical study in rabbit tibias (2009). 1531-5053 (Electronic)Google Scholar
  39. Fahami, A., Nasiri-Tabrizi, B., Ebrahimi-Kahrizsangi, R.: Mechanosynthesis and characterization of chlorapatite nanopowders. Mater. Lett. 110, 117–121 (2013)CrossRefGoogle Scholar
  40. Ferraz, M., Mateus, A., Sousa, J., Monteiro, F.: Nanohydroxyapatite microspheres as delivery system for antibiotics: release kinetics, antimicrobial activity, and interaction with osteoblasts. J. Biomed. Mater. Res., Part A 81(4), 994–1004 (2007)CrossRefGoogle Scholar
  41. Fu, L.-H., Chao, Q., Liu, Y.-J., Cao, W.-T., Ma, M.-G.: Sonochemical synthesis of cellulose/hydroxyapatite nanocomposites and their application in protein adsorption. Sci. Rep. 8(1) (2018)Google Scholar
  42. Furko, M., Havasi, V., Kónya, Z., Grünewald, A., Detsch, R., Boccaccini, A.R., Balázsi, C.: Development and characterization of multi-element doped hydroxyapatite bioceramic coatings on metallic implants for orthopedic applications. Boletín de la Sociedad Española de Cerámica y Vidrio 57(2), 55–65 (2018)CrossRefGoogle Scholar
  43. Furlong, R., Osborn, J.: Fixation of hip prostheses by hydroxyapatite ceramic coatings. Bone Joint J. 73(5), 741–745 (1991)Google Scholar
  44. Furukawa, T., Matsusue, Y., Yasunaga, T., Nakagawa, Y., Okada, Y., Shikinami, Y., Okuno, M., Nakamura, T.: Histomorphometric study on high-strength hydroxyapatite/poly(L-lactide) composite rods for internal fixation of bone fractures. J. Biomed. Mater. Res. 50(3), 410–419 (2000)CrossRefGoogle Scholar
  45. Gauthier, O., Bouler, J.M., Weiss, P., Bosco, J., Aguado, E., Daculsi, G.: Short-term effects of mineral particle sizes on cellular degradation activity after implantation of injectable calcium phosphate biomaterials and the consequences for bone substitution. Bone 25(2), 71S–74S (1999)CrossRefGoogle Scholar
  46. Gholizadeh, B.S., Buazar, F., Hosseini, S.M., Mousavi, S.M.: Enhanced antibacterial activity, mechanical and physical properties of alginate/hydroxyapatite bionanocomposite film (2018). 1879-0003 (Electronic)Google Scholar
  47. Giacomini, D., Torricelli, P., Gentilomi, G.A., Boanini, E., Gazzano, M., Bonvicini, F., Benetti, E., Soldati, R., Martelli, G., Rubini, K., Bigi, A.: Monocyclic β-lactams loaded on hydroxyapatite: new biomaterials with enhanced antibacterial activity against resistant strains. Sci. Rep. 7(1), 2712 (2017)CrossRefGoogle Scholar
  48. Gratton, S.E.A., Ropp, P.A., Pohlhaus, P.D., Luft, J.C., Madden, V.J., Napier, M.E., DeSimone, J.M.: The effect of particle design on cellular internalization pathways. Proc. Natl. Acad. Sci. 105(33), 11613–11618 (2008)CrossRefGoogle Scholar
  49. Gu, Y.W., Khor, K.A., Cheang, P.: Bone-like apatite layer formation on hydroxyapatite prepared by spark plasma sintering (SPS). Biomaterials 25(18), 4127–4134 (2004)CrossRefGoogle Scholar
  50. Guo, Y.-P., Yao, Y.-B., Ning, C.-Q., Guo, Y.-J., Chu, L.-F.: Fabrication of mesoporous carbonated hydroxyapatite microspheres by hydrothermal method. Mater. Lett. 65(14), 2205–2208 (2011)CrossRefGoogle Scholar
  51. Ha, S.-W., Jang, H.L., Nam, K.T., Beck, G.R.: Nano-hydroxyapatite modulates osteoblast lineage commitment by stimulation of DNA methylation and regulation of gene expression. Biomaterials 65, 32–42 (2015)CrossRefGoogle Scholar
  52. Habibovic, P., Kruyt, M.C., Juhl, M.V., Clyens, S., Martinetti, R., Dolcini, L., Theilgaard, N., van Blitterswijk, C.A.: Comparative in vivo study of six hydroxyapatite-based bone graft substitutes. J. Orthop. Res. 26(10), 1363–1370 (2008)CrossRefGoogle Scholar
  53. Hamdy, M.S., Awwad, N.S., Alshahrani, A.M.: Mesoporous magnesia: synthesis, characterization, adsorption behavior and cytotoxic activity. Mater. Des. 110, 503–509 (2016)CrossRefGoogle Scholar
  54. Hanes, P.J., Purvis, J.P.: Local anti-infective therapy: pharmacological agents. A systematic review. Ann. Periodontol. 8(1), 79–98 (2003)CrossRefGoogle Scholar
  55. Hannig, C., Basche, S., Burghardt, T., Al-Ahmad, A., Hannig, M.: Influence of a mouthwash containing hydroxyapatite microclusters on bacterial adherence in situ. Clin. Oral Invest. 17(3), 805–814 (2013)CrossRefGoogle Scholar
  56. Harja, M., Ciobanu, G.: Studies on adsorption of oxytetracycline from aqueous solutions onto hydroxyapatite (2018). 1879-1026 (Electronic)Google Scholar
  57. Hashimoto, Y., Taki, T., Sato, T.: Sorption of dissolved lead from shooting range soils using hydroxyapatite amendments synthesized from industrial byproducts as affected by varying pH conditions. J. Environ. Manage. 90(5), 1782–1789 (2009)CrossRefGoogle Scholar
  58. Hassan, M.I., Sultana, N.: Characterization, drug loading and antibacterial activity of nanohydroxyapatite/polycaprolactone (nHA/PCL) electrospun membrane. 3 Biotech 7(4), 249 (2017)Google Scholar
  59. Hiller, K.-A., Buchalla, W., Grillmeier, I., Neubauer, C., Schmalz, G.: In vitro effects of hydroxyapatite containing toothpastes on dentin permeability after multiple applications and ageing. Sci. Rep. 8(1), 4888 (2018)CrossRefGoogle Scholar
  60. Hou, C.-H., Hou, S.-M., Hsueh, Y.-S., Lin, J., Wu, H.-C., Lin, F.-H.: The in vivo performance of biomagnetic hydroxyapatite nanoparticles in cancer hyperthermia therapy. Biomaterials 30(23), 3956–3960 (2009)CrossRefGoogle Scholar
  61. Hu, J., Russell, J., Ben-Nissan, B., Vago, R.: Production and analysis of hydroxyapatite from Australian corals via hydrothermal process. J. Mater. Sci. Lett. 20(1), 85–87 (2001)CrossRefGoogle Scholar
  62. Hu, Y., Gu, X., Yang, Y., Huang, J., Hu, M., Chen, W., Tong, Z., Wang, C.: Facile fabrication of poly(L-lactic acid)-grafted hydroxyapatite/poly(lactic-co-glycolic acid) scaffolds by pickering high internal phase emulsion templates. ACS Appl. Mater. Interfaces 6(19), 17166–17175 (2014)CrossRefGoogle Scholar
  63. Huang, S., Gao, S., Cheng, L., Yu, H.: Remineralization potential of nano-hydroxyapatite on initial enamel lesions: an in vitro study. Caries Res. 45(5), 460–468 (2011)CrossRefGoogle Scholar
  64. Huang, Z.-B., Shi, X., Mao, J., Gong, S.-Q.: Design of a hydroxyapatite-binding antimicrobial peptide with improved retention and antibacterial efficacy for oral pathogen control. Sci. Rep. 6, 38410 (2016)CrossRefGoogle Scholar
  65. Itokazu, M., Sugiyama, T., Ohno, T., Wada, E., Katagiri, Y.: Development of porous apatite ceramic for local delivery of chemotherapeutic agents. J. Biomed. Mater. Res.: Off. J. Soc. Biomater., Jpn. Soc. Biomater., Aust. Soc. Biomater. 39(4), 536–538 (1998a)CrossRefGoogle Scholar
  66. Itokazu, M., Yang, W., Aoki, T., Ohara, A., Kato, N.: Synthesis of antibiotic-loaded interporous hydroxyapatite blocks by vacuum method and in vitro drug release testing. Biomaterials 19(7), 817–819 (1998b)CrossRefGoogle Scholar
  67. Jarlbring, M., Sandström, D.E., Antzutkin, O.N., Forsling, W.: Characterization of active phosphorus surface sites at synthetic carbonate-free fluorapatite using single-pulse 1H, 31P, and 31P CP MAS NMR. Langmuir 22(10), 4787–4792 (2006)CrossRefGoogle Scholar
  68. Jayasree, R., Kumar, T.S., Mahalaxmi, S., Abburi, S., Rubaiya, Y., Doble, M.: Dentin remineralizing ability and enhanced antibacterial activity of strontium and hydroxyl ion co-releasing radiopaque hydroxyapatite cement. J. Mater. Sci. Mater. Med. 28(6), 95 (2017)CrossRefGoogle Scholar
  69. Jee, S.S., Kasinath, R.K., DiMasi, E., Kim, Y.-Y., Gower, L.: Oriented hydroxyapatite in turkey tendon mineralized via the polymer-induced liquid-precursor (PILP) process. CrystEngComm 13(6), 2077–2083 (2011)CrossRefGoogle Scholar
  70. Jungbauer, A., Hahn, R., Deinhofer, K., Luo, P.: Performance and characterization of a nanophased porous hydroxyapatite for protein chromatography. Biotechnol. Bioeng. 87(3), 364–375 (2004)CrossRefGoogle Scholar
  71. Juntavee, N., Juntavee, A., Plongniras, P.: Remineralization potential of nano-hydroxyapatite on enamel and cementum surrounding margin of computer-aided design and computer-aided manufacturing ceramic restoration (2018). 1178-2013 (Electronic)CrossRefGoogle Scholar
  72. Kang, M.-H., Jung, H.-D., Kim, S.-W., Lee, S.-M., Kim, H.-E., Estrin, Y., Koh, Y.-H.: Production and bio-corrosion resistance of porous magnesium with hydroxyapatite coating for biomedical applications. Mater. Lett. 108, 122–124 (2013)CrossRefGoogle Scholar
  73. Karthik, A., Vinita, V., Gobi Saravanan, K., Viswanathan, K., Chavali, M.: Implant application of bioactive nano-hydroxyapatite powders—a comparative study. Mater. Res. Express 5(1), 015405 (2018)CrossRefGoogle Scholar
  74. Ke, D., Robertson, S.F., Dernell, W.S., Bandyopadhyay, A., Bose, S.: Effects of MgO and SiO2 on plasma-sprayed hydroxyapatite coating: an in vivo study in rat distal femoral defects. ACS Appl. Mater. Interfaces 9(31), 25731–25737 (2017)CrossRefGoogle Scholar
  75. Kensche, A., Pötschke, S., Hannig, C., Richter, G., Hoth-Hannig, W., Hannig, M.: Influence of calcium phosphate and apatite containing products on enamel erosion. Sci. World J. 2016, 12 (2016)Google Scholar
  76. Kensche, A., Holder, C., Basche, S., Tahan, N., Hannig, C., Hannig, M.: Efficacy of a mouthrinse based on hydroxyapatite to reduce initial bacterial colonisation in situ. Arch. Oral Biol. 80, 18–26 (2017)CrossRefGoogle Scholar
  77. Khajuria, D.K., Kumar, V.B., Gedanken, A., Karasik, D.: Accelerated bone regeneration by nitrogen-doped carbon dots functionalized with hydroxyapatite nanoparticles. LID (2018). 1944-8252 (Electronic)CrossRefGoogle Scholar
  78. Khanarian, N.T., Haney, N.M., Burga, R.A., Lu, H.H.: A functional agarose-hydroxyapatite scaffold for osteochondral interface regeneration. Biomaterials 33(21), 5247–5258 (2012)CrossRefGoogle Scholar
  79. Khanna, K., Jaiswal, A., Dhumal, R.V., Selkar, N., Chaudhari, P., Soni, V.P., Vanage, G.R., Bellare, J.: Comparative bone regeneration study of hardystonite and hydroxyapatite as filler in critical-sized defect of rat calvaria. RSC Adv. 7(60), 37522–37533 (2017)CrossRefGoogle Scholar
  80. Kim, T.N., Feng, Q.L., Kim, J.O., Wu, J., Wang, H., Chen, G.C., Cui, F.Z.: Antimicrobial effects of metal ions (Ag+,  Cu2+, Zn2+) in hydroxyapatite. J. Mater. Sci. Mater. Med. 9(3), 129–134 (1998)CrossRefGoogle Scholar
  81. Kim, H.-W., Kim, H.-E., Knowles, J.C.: Fluor-hydroxyapatite sol-gel coating on titanium substrate for hard tissue implants. Biomaterials 25(17), 3351–3358 (2004a)CrossRefGoogle Scholar
  82. Kim, H.W., Koh, Y.H., Li, L.H., Lee, S., Kim, H.E.: Hydroxyapatite coating on titanium substrate with titania buffer layer processed by sol-gel method. Biomaterials 25(13), 2533–2538 (2004b)CrossRefGoogle Scholar
  83. Kim, J.S., Kuk, E., Yu, K.N., Kim, J.-H., Park, S.J., Lee, H.J., Kim, S.H., Park, Y.K., Park, Y.H., Hwang, C.-Y.: Antimicrobial effects of silver nanoparticles. Nanomedicine: Nanotechnol., Biol. Med. 3(1), 95–101 (2007)Google Scholar
  84. Klesing, J., Chernousova, S., Epple, M.: Freeze-dried cationic calcium phosphatenanorods as versatile carriers of nucleic acids (DNA, siRNA). J. Mater. Chem. 22(1), 199–204 (2012)CrossRefGoogle Scholar
  85. Kokubo, T., Takadama, H.: How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 27(15), 2907–2915 (2006)CrossRefGoogle Scholar
  86. Kolanthai, E., Ganesan, K., Epple, M., Kalkura, S.N.: Synthesis of nanosized hydroxyapatite/agarose powders for bone filler and drug delivery application. Mater. Today Commun. 8, 31–40 (2016)CrossRefGoogle Scholar
  87. Kong, L., Gao, Y., Cao, W., Gong, Y., Zhao, N., Zhang, X.: Preparation and characterization of nano-hydroxyapatite/chitosan composite scaffolds. J. Biomed. Mater. Res., Part A 75A(2), 275–282 (2005)CrossRefGoogle Scholar
  88. Kong, L., Mu, Z., Yu, Y., Zhang, L., Hu, J.: Polyethyleneimine-stabilized hydroxyapatite nanoparticles modified with hyaluronic acid for targeted drug delivery. RSC Adv. 6(104), 101790–101799 (2016)CrossRefGoogle Scholar
  89. Krishnan, A.G., Jayaram, L., Biswas, R., Nair, M.: Evaluation of antibacterial activity and cytocompatibility of ciprofloxacin loaded Gelatin–Hydroxyapatite scaffolds as a local drug delivery system for osteomyelitis treatment. Tissue Eng., Part A 21(7–8), 1422–1431 (2015)CrossRefGoogle Scholar
  90. Kundu, B., Ghosh, D., Sinha, M.K., Sen, P.S., Balla, V.K., Das, N., Basu, D.: Doxorubicin-intercalated nano-hydroxyapatite drug-delivery system for liver cancer: an animal model. Ceram. Int. 39(8), 9557–9566 (2013)CrossRefGoogle Scholar
  91. Kurtjak, M., Vukomanović, M., Kramer, L., Suvorov, D.: Biocompatible nano-gallium/hydroxyapatite nanocomposite with antimicrobial activity. J. Mater. Sci. Mater. Med. 27(11), 170 (2016)CrossRefGoogle Scholar
  92. Kwak, D.H., Lee, E.J., Kim, D.J.: Bioactivity of cellulose acetate/hydroxyapatite nanoparticle composite fiber by an electro-spinning process. J. Nanosci. Nanotechnol. 14(11), 8464–8471 (2014)CrossRefGoogle Scholar
  93. Larsen, M.J., Fejerkov, O.: Chemical and structural challenges in remineralization of dental enamel lesions. Eur. J. Oral Sci. 97(4), 285–296 (1989)CrossRefGoogle Scholar
  94. Li, M., Xiong, P., Yan, F., Li, S., Ren, C., Yin, Z, Li, A., Li, H., Ji, X., Zheng, Y., Cheng, Y.: An overview of graphene-based hydroxyapatite composites for orthopedic applications (2018). 2452-199X (Electronic)Google Scholar
  95. Li, S.H., De Wijn, J.R., Layrolle, P., de Groot, K.: Synthesis of macroporous hydroxyapatite scaffolds for bone tissue engineering. J. Biomed. Mater. Res. 61(1), 109–120 (2002)CrossRefGoogle Scholar
  96. Li, B., Guo, B., Fan, H., Zhang, X.: Preparation of nano-hydroxyapatite particles with different morphology and their response to highly malignant melanoma cells in vitro. Appl. Surf. Sci. 255(2), 357–360 (2008a)CrossRefGoogle Scholar
  97. Li, J., Yin, Y., Yao, F., Zhang, L., Yao, K.: Effect of nano- and micro-hydroxyapatite/chitosan-gelatin network film on human gastric cancer cells. Mater. Lett. 62(17), 3220–3223 (2008b)CrossRefGoogle Scholar
  98. Li, L., Liu, Y., Tao, J., Zhang, M., Pan, H., Xu, X., Tang, R.: Surface modification of hydroxyapatite nanocrystallite by a small amount of terbium provides a biocompatible fluorescent probe. J. Phys. Chem. C 112(32), 12219–12224 (2008c)CrossRefGoogle Scholar
  99. Liang, C., Joseph, M.M., James, C.M.L., Hao, L.: The role of surface charge on the uptake and biocompatibility of hydroxyapatite nanoparticles with osteoblast cells. Nanotechnology 22(10), 105708 (2011)CrossRefGoogle Scholar
  100. Lin, K., Pan, J., Chen, Y., Cheng, R., Xu, X.: Study the adsorption of phenol from aqueous solution on hydroxyapatite nanopowders. J. Hazard. Mater. 161(1), 231–240 (2009)CrossRefGoogle Scholar
  101. Liu, D.-M.: Fabrication and characterization of porous hydroxyapatite granules. Biomaterials 17(20), 1955–1957 (1996)CrossRefGoogle Scholar
  102. Lukasheva, N.V., Tolmachev, D.A.: Cellulose nanofibrils and mechanism of their mineralization in biomimetic synthesis of hydroxyapatite/native bacterial cellulose nanocomposites: molecular dynamics simulations. Langmuir 32(1), 125–134 (2015)CrossRefGoogle Scholar
  103. Lv, Q., Nair, L., Laurencin, C.T.: Fabrication, characterization, and in vitro evaluation of poly(lactic acid glycolic acid)/nano-hydroxyapatite composite microsphere-based scaffolds for bone tissue engineering in rotating bioreactors. J. Biomed. Mater. Res. A 91(3), 679–691 (2009)CrossRefGoogle Scholar
  104. Ma, Q.Y., Traina, S.J., Logan, T.J., Ryan, J.A.: Effects of Aqueous Al, Cd, Cu, Fe(II), Ni, and Zn on Pb immobilization by hydroxyapatite. Environ. Sci. Technol. 28(7), 1219–1228 (1994)CrossRefGoogle Scholar
  105. Madhumathi, K., Rubaiya, Y., Doble, M., Venkateswari, R., Sampath Kumar, T.S.: Antibacterial, anti-inflammatory, and bone-regenerative dual-drug-loaded calcium phosphate nanocarriers-in vitro and in vivo studies. LID (2018). 2190-3948 (Electronic)CrossRefGoogle Scholar
  106. Mahdi, S., Ramin, R., Fabio, S., Maliheh, G., Michael, S.: Synthesis of stabilized hydroxyapatite nanosuspensions for enamel caries remineralization. Aust. Dent. J. 63, 356–364 (2018). Scholar
  107. Mahabole, M.P., Aiyer, R.C., Ramakrishna, C.V., Sreedhar, B., Khairnar, R.S.: Synthesis, characterization and gas sensing property of hydroxyapatite ceramic. Bull. Mater. Sci. 28(6), 535–545 (2005)CrossRefGoogle Scholar
  108. Maia, A.L., Cavalcante, C.H., Souza, M.G., Ferreira Cde, A., Rubello, D., Chondrogiannis, S., Cardoso, V.N., Ramaldes, G.A., Barros, A.L., Soares, D.C.: Hydroxyapatite nanoparticles. Nucl. Med. Commun. 37(7), 775–782 (2016)CrossRefGoogle Scholar
  109. Maia, A. L. C.: Vincristine-loaded hydroxyapatite nanoparticles as a potential delivery system for bone cancer therapy. (2018). CrossRefGoogle Scholar
  110. Malmberg, P., Nygren, H.: Methods for the analysis of the composition of bone tissue, with a focus on imaging mass spectrometry (TOF-SIMS). Proteomics 8(18), 3755–3762 (2008)CrossRefGoogle Scholar
  111. Marini, E., Ballanti, P., Silvestrini, G., Valdinucci, F., Bonucci, E.: The presence of different growth factors does not influence bone response to hydroxyapatite: preliminary results. J. Orthop. Andtraumatology 5(1), 34–43 (2004)CrossRefGoogle Scholar
  112. Meagher, M.J., Weiss-Bilka, H.E., Best, M.E., Boerckel, J.D., Wagner, D.R., Roeder, R.K.: Acellular hydroxyapatite-collagen scaffolds support angiogenesis and osteogenic gene expression in an ectopic murine model: effects of hydroxyapatite volume fraction. J. Biomed. Mater. Res., Part A 104(9), 2178–2188 (2016)CrossRefGoogle Scholar
  113. Mombelli, A.: Periodontitis as an infectious disease: specific features and their implications. Oral Dis. 9(s1), 6–10 (2003)CrossRefGoogle Scholar
  114. Munir, M.U., Ihsan, A., Sarwar, Y., Bajwa, S.Z., Bano, K., Tehseen, B., Zeb, N., Hussain, I., Ansari, M.T., Saeed, M., Li, J., Iqbal, M.Z., Wu, A., Khan, W.S.: Hollow mesoporous hydroxyapatite nanostructures; smart nanocarriers with high drug loading and controlled releasing features. Int. J. Pharm. 544(1), 112–120 (2018)CrossRefGoogle Scholar
  115. Nancy, D., Rajendran, N.: Vancomycin incorporated chitosan/gelatin coatings coupled with TiO2–SrHAP surface modified cp-titanium for osteomyelitis treatment. Int. J. Biol. Macromol. 110, 197–205 (2018)CrossRefGoogle Scholar
  116. Nasiri-Tabrizi, B., Fahami, A.: Synthesis and characterization of chlorapatite–ZnO composite nanopowders. Ceram. Int. 40(2), 2697–2706 (2014)CrossRefGoogle Scholar
  117. Nasri, K., El Feki, H., Sharrock, P., Fiallo, M., Nzihou, A.: Spray-dried monocalcium phosphate monohydrate for soluble phosphate fertilizer. Ind. Eng. Chem. Res. 54(33), 8043–8047 (2015)CrossRefGoogle Scholar
  118. Netz, D.J.A., Sepulveda, P., Pandolfelli, V.C., Spadaro, A.C.C., Alencastre, J.B., Bentley, M.V.L.B., Marchetti, J.M.: Potential use of gelcasting hydroxyapatite porous ceramic as an implantable drug delivery system. Int. J. Pharm. 213(1–2), 117–125 (2001)CrossRefGoogle Scholar
  119. Nozari, A., Ajami, S., Rafiei, A., Niazi, E.: Impact of nano hydroxyapatite, nano silver fluoride and sodium fluoride varnish on primary teeth enamel remineralization: an in vitro study (2017). 2249-782X (Print)Google Scholar
  120. O’Hare, P., Meenan, B.J., Burke, G.A., Byrne, G., Dowling, D., Hunt, J.A.: Biological responses to hydroxyapatite surfaces deposited via a co-incident microblasting technique. Biomaterials 31(3), 515–522 (2010)CrossRefGoogle Scholar
  121. Olsson, C., Emilson, C., Birkhed, D.: An in vitro study of fluoride release from a resin-modified glass ionomer cement after exposure to toothpaste slurries of different pH. Clin. Oral Invest. 4(4), 233–237 (2000)CrossRefGoogle Scholar
  122. Ong, J.L., Chan, D.C.: Hydroxyapatite and their use as coatings in dental implants: a review (2000). 0278-940X (Print)Google Scholar
  123. Oonishi, H., Hench, L., Wilson, J., Sugihara, F., Tsuji, E., Kushitani, S., Iwaki, H.: Comparative bone growth behavior in granules of bioceramic materials of various sizes. J. Biomed. Mater. Res.: Off. J. Soc. Biomater., Jpn. Soc. Biomater., Aust. Soc. Biomater. 44(1), 31–43 (1999)CrossRefGoogle Scholar
  124. Otsuka, M., Matsuda, Y., Suwa, Y., Fox, J.L., Higuchi, W.I.: A novel skeletal drug-delivery system using self-setting calcium phosphate cement. 4. Effects of the mixing solution volume on the drug-release rate of heterogeneous aspirin-loaded cement. J. Pharm. Sci. 83(2), 259–263 (1994)CrossRefGoogle Scholar
  125. Palazzo, B., Iafisco, M., Laforgia, M., Margiotta, N., Natile, G., Bianchi, C.L., Walsh, D., Mann, S., Roveri, N.: Biomimetic hydroxyapatite-drug nanocrystals as potential bone substitutes with antitumour drug delivery properties. Adv. Func. Mater. 17(13), 2180–2188 (2007)CrossRefGoogle Scholar
  126. Pandey, A., Midha, S., Sharma, R.K., Maurya, R., Nigam, V.K., Ghosh, S., Balani, K.: Antioxidant and antibacteria hydroxyapatite-based biocomposite for orthopedic applications (2018). 1873-0191 (Electronic)Google Scholar
  127. Park, H.-K., Lee, S.J., Oh, J.-S., Lee, S.-G., Jeong, Y.-I.L., Lee, H.C.: Smart nanoparticles based on hyaluronic acid for redox-responsive and CD44 receptor-mediated targeting of tumour. Nanoscale Res. Lett. 10(1), 981 (2015)Google Scholar
  128. Pelin, I.M., Maier, S.S., Chitanu, G.C., Bulacovschi, V.: Preparation and characterization of a hydroxyapatite–collagen composite as component for injectable bone substitute. Mater. Sci. Eng., C 29(7), 2188–2194 (2009)CrossRefGoogle Scholar
  129. Piccirillo, C., L Castro, P.M.: Calcium hydroxyapatite-based photocatalysts for environment remediation: characteristics, performances and future perspectives (2017). 1095-8630 (Electronic)Google Scholar
  130. Predoi, D., Popa, C.L., Chapon, P., Groza, A., Iconaru, S.L.: Evaluation of the antimicrobial activity of different antibiotics enhanced with silver-doped hydroxyapatite thin films. LID E778 [pii] (2016). 1996-1944 (Print)CrossRefGoogle Scholar
  131. Rabiei, A., Blalock, T., Thomas, B., Cuomo, J., Yang, Y., Ong, J.: Microstructure, mechanical properties, and biological response to functionally graded HA coatings. Mater. Sci. Eng., C 27(3), 529–533 (2007)CrossRefGoogle Scholar
  132. Rabinovich-Guilatt, L., Couvreur, P., Lambert, G., Dubernet, C.: Cationic vectors in ocular drug delivery. J. Drug Target. 12(9–10), 623–633 (2004)CrossRefGoogle Scholar
  133. Raucci, M.G., Demitri, C., Soriente, A., Fasolino, I., Sannino, A., Ambrosio, L.: Gelatin/nano‐hydroxyapatite hydrogel scaffold prepared by sol‐gel technology as filler to repair bone defects. J. Biomed. Mater. Res. 106(7), 2007–2019 Part A (2018). Wiley. ISSN: 1549-3296. Scholar
  134. Riaz, M., Zia, R., Ijaz, A., Hussain, T., Mohsin, M., Malik, A.: Synthesis of monophasic Ag doped hydroxyapatite and evaluation of antibacterial activity (2018). 1873-0191 (Electronic)Google Scholar
  135. Roveri, N., Battistella, E., Foltran, I., Foresti, E., Iafisco, M., Lelli, M., Palazzo, B., Rimondini, L.: Synthetic biomimetic carbonate-hydroxyapatite nanocrystals for enamel remineralization. Adv. Mater. Res. 47–50, 821–824 (2008)CrossRefGoogle Scholar
  136. Sadat-Shojai, M., Atai, M., Nodehi, A., Khanlar, L.N.: Hydroxyapatite nanorods as novel fillers for improving the properties of dental adhesives: synthesis and application. Dent. Mater. 26(5), 471–482 (2010)CrossRefGoogle Scholar
  137. Sadat-Shojai, M., Khorasani, M.-T., Dinpanah-Khoshdargi, E., Jamshidi, A.: Synthesis methods for nanosized hydroxyapatite with diverse structures. Acta Biomater. 9(8), 7591–7621 (2013)CrossRefGoogle Scholar
  138. Sakamoto, A., Okamoto, T., Matsuda, S.: Unsintered hydroxyapatite and poly-l-lactide composite screws/plates for stabilizing beta-tricalcium phosphate bone implants (2018). 2005-4408 (Electronic)Google Scholar
  139. Sampath Kumar, T.S., Madhumathi, K., Rubaiya, Y., Doble, M.: Dual mode antibacterial activity of ion substituted calcium phosphate nanocarriers for bone infections (2015). 2296-4185 (Print)Google Scholar
  140. Sanjay, M., Madhu, P., Jawaid, M., Senthamaraikannan, P., Senthil, S., Pradeep, S.: Characterization and properties of natural fiber polymer composites: comprehensive review. J. Clean. Prod. 172, 566–581 (2018)CrossRefGoogle Scholar
  141. Sato, K.: Mechanism of hydroxyapatite mineralization in biological systems (review). J. Ceram. Soc. Jpn. 115(1338), 124–130 (2007)CrossRefGoogle Scholar
  142. Sato, T., Kikuchi, M., Aizawa, M.: Preparation of hydroxyapatite/collagen injectable bone paste with an anti-washout property utilizing sodium alginate. Part 1: influences of excess supplementation of calcium compounds. J. Mater. Sci. Mater. Med. 28(3), 49 (2017)CrossRefGoogle Scholar
  143. Schreurs, W., Rosenberg, H.: Effect of silver ions on transport and retention of phosphate by Escherichia coli. J. Bacteriol. 152(1), 7–13 (1982)Google Scholar
  144. Seol, Y.-J., Kim, J.Y., Park, E.K., Kim, S.-Y., Cho, D.-W.: Fabrication of a hydroxyapatite scaffold for bone tissue regeneration using microstereolithography and molding technology. Microelectron. Eng. 86(4), 1443–1446 (2009)CrossRefGoogle Scholar
  145. Shahmoradi, M., Rohanizadeh, R., Sonvico, F., Ghadiri, M., Swain, M.: Synthesis of stabilized hydroxyapatite nanosuspensions for enamel caries remineralization. LID (2018). 1834-7819 (Electronic)CrossRefGoogle Scholar
  146. Shanmugam, S., Gopal, B.: Copper substituted hydroxyapatite and fluorapatite: synthesis, characterization and antimicrobial properties. Ceram. Int. 40(10, Part A), 15655–15662 (2014)CrossRefGoogle Scholar
  147. Slots, J., Ting, M.: Systemic antibiotics in the treatment of periodontal disease. Periodontology 2000 28(1), 106–176 (2002)CrossRefGoogle Scholar
  148. Son, J.S., Appleford, M., Ong, J.L., Wenke, J.C., Kim, J.M., Choi, S.H., Oh, D.S.: Porous hydroxyapatite scaffold with three-dimensional localized drug delivery system using biodegradable microspheres. J. Control. Release 153(2), 133–140 (2011)CrossRefGoogle Scholar
  149. Stamm, W.E.: Infections related to medical devices. Ann. Intern. Med. 89(5, Part_2), 764–769 (1978)CrossRefGoogle Scholar
  150. Stanić, V., Dimitrijević, S., Antić-Stanković, J., Mitrić, M., Jokić, B., Plećaš, I.B., Raičević, S.: Synthesis, characterization and antimicrobial activity of copper and zinc-doped hydroxyapatite nanopowders. Appl. Surf. Sci. 256(20), 6083–6089 (2010)CrossRefGoogle Scholar
  151. Strietzel, F.P., Reichart, P.A., Graf, H.L.: Lateral alveolar ridge augmentation using a synthetic nano-crystalline hydroxyapatite bone substitution material (Ostim): preliminary clinical and histological results. Clin. Oral Implant. Res. 18(6), 743–751 (2007)CrossRefGoogle Scholar
  152. Suchanek, W., Yoshimura, M.: Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants. J. Mater. Res. 13(01), 94–117 (1998)CrossRefGoogle Scholar
  153. Sugiyama, S., Minami, T., Hayashi, H., Tanaka, M., Shigemoto, N., Moffat, J.B.: Partial oxidation of methane to carbon oxides and hydrogen on hydroxyapatite: enhanced selectivity to carbon monoxide with tetrachloromethane. Energy Fuels 10(3), 828–830 (1996)CrossRefGoogle Scholar
  154. Sumer, B., Gao, J.: Theranostic nanomedicine for cancer. Nanomedicine 3(2), 137–140 (2008)CrossRefGoogle Scholar
  155. Sun, W., Fan, J., Wang, S., Kang, Y., Du, J., Peng, X.: Biodegradable drug-loaded hydroxyapatite nanotherapeutic agent for targeted drug release in tumours. ACS Appl. Mater. Interfaces. 10(9), 7832–7840 (2018)CrossRefGoogle Scholar
  156. Sundararaj, S.C., Thomas, M.V., Peyyala, R., Dziubla, T.D., Puleo, D.A.: Design of a multiple drug delivery system directed at periodontitis. Biomaterials 34(34), 8835–8842 (2013)CrossRefGoogle Scholar
  157. Tadashi, K., Seishi, E., Keiko, M., Yuji, T., Tetsu, T., Osamu, S., Shinji, K.: First clinical application of octacalcium phosphate collagen composite in human bone defect. Tissue Eng., Part A 20(7–8), 1336–1341 (2014)Google Scholar
  158. Tao, Z.S., Zhou, W.S., Qiang, Z., Tu, K.K., Huang, Z.L., Xu, H.M., Sun, T., Lv, Y.X., Cui, W., Yang, L.: Intermittent administration of human parathyroid hormone (1–34) increases fixation of strontium-doped hydroxyapatite coating titanium implants via electrochemical deposition in ovariectomized rat femur (2016). 1530-8022 (Electronic)Google Scholar
  159. Tao, Z.S., Bai, B.L., He, X.W., Liu, W., Li, H., Zhou, Q., Sun, T., Huang, Z.L., Tu, K.K., Lv, Y.X., Cui, W., Yang, L.: A comparative study of strontium-substituted hydroxyapatite coating on implant’s osseointegration for osteopenic rats (2016). 1741-0444 (Electronic)Google Scholar
  160. Tao, Z.-S., Zhou, W.-S., He, X.-W., Liu, W., Bai, B.-L., Zhou, Q., Huang, Z.-L., Tu, K.-K., Li, H., Sun, T., Lv, Y.-X., Cui, W., Yang, L.: A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats. Mater. Sci. Eng. C 62, 226–232 (2016)CrossRefGoogle Scholar
  161. Torres, J., Tamimi, I., Cabrejos-Azama, J., Tresguerres, I., Alkhraisat, M., López-Cabarcos, E., Hernández, G., Tamimi, F.: Monetite granules versus particulate autologous bone in bone regeneration. Ann. Anat. Anatomischer Anzeiger 200, 126–133 (2015)CrossRefGoogle Scholar
  162. Tripathi, G., Basu, B.: A porous hydroxyapatite scaffold for bone tissue engineering: physico-mechanical and biological evaluations. Ceram. Int. 38(1), 341–349 (2012)CrossRefGoogle Scholar
  163. Trombelli, L., Simonelli, A., Pramstraller, M., Wikesjö, U.M.E., Farina, R.: Single flap approach with and without guided tissue regeneration and a hydroxyapatite biomaterial in the management of intraosseous periodontal defects. J. Periodontol. 81(9), 1256–1263 (2010)CrossRefGoogle Scholar
  164. Tschoppe, P., Zandim, D.L., Martus, P., Kielbassa, A.M.: Enamel and dentine remineralization by nano-hydroxyapatite toothpastes. J. Dent. 39(6), 430–437 (2011)CrossRefGoogle Scholar
  165. Uchida, A., Shinto, Y., Araki, N., Ono, K.: Slow release of anticancer drugs from porous calcium hydroxyapatite ceramic. J. Orthop. Res. 10(3), 440–445 (1992)CrossRefGoogle Scholar
  166. Uskoković, V., Desai, T.A.: In vitro analysis of nanoparticulate hydroxyapatite/chitosan composites as potential drug delivery platforms for the sustained release of antibiotics in the treatment of osteomyelitis. J. Pharm. Sci. 103(2), 567–579 (2014)CrossRefGoogle Scholar
  167. Uskokovic, V., Ghosh, S., Wu, V.M.: Antimicrobial hydroxyapatite-gelatin-silica composite pastes with tunable setting properties (2017). 2050-750X (Print)Google Scholar
  168. Vahabzadeh, S., Roy, M., Bandyopadhyay, A., Bose, S.: Phase stability and biological property evaluation of plasma sprayed hydroxyapatite coatings for orthopedic and dental applications. Acta Biomater. 17, 47–55 (2015)CrossRefGoogle Scholar
  169. Vallet-Regí, M., González-Calbet, J.M.: Calcium phosphates as substitution of bone tissues. Prog. Solid State Chem. 32(1), 1–31 (2004)CrossRefGoogle Scholar
  170. Vano, M., Derchi, G., Barone, A., Pinna, R., Usai, P., Covani, U.: Reducing dentine hypersensitivity with nano-hydroxyapatite toothpaste: a double-blind randomized controlled trial. Clin. Oral Invest. 22(1), 313–320 (2018)CrossRefGoogle Scholar
  171. Vasir, J.K., Labhasetwar, V.: Quantification of the force of nanoparticle-cell membrane interactions and its influence on intracellular trafficking of nanoparticles. Biomaterials 29(31), 4244–4252 (2008)CrossRefGoogle Scholar
  172. Venkatasubbu, G.D., Ramasamy, S., Avadhani, G.S., Ramakrishnan, V., Kumar, J.: Surface modification and paclitaxel drug delivery of folic acid modified polyethylene glycol functionalized hydroxyapatite nanoparticles. Powder Technol. 235, 437–442 (2013)CrossRefGoogle Scholar
  173. Vyavhare, S., Sharma, D.S., Kulkarni,V.K.: Effect of three different pastes on remineralization of initial enamel lesion: an in vitro study (2015). 1053-4628 (Print)Google Scholar
  174. Wahl, D.A., Czernuszka, J.T.: Collagen-hydroxyapatite composites for hard tissue repair. Eur. Cells Mater. 11, 43–56 (2006)CrossRefGoogle Scholar
  175. Wang, L., Nancollas, G.H.: Pathways to biomineralization and biodemineralization of calcium phosphates: the thermodynamic and kinetic controls. Dalton Trans. (15), 2665–2672 (2009)Google Scholar
  176. Wang, Y., Liu, L., Guo, S.: Characterization of biodegradable and cytocompatible nano-hydroxyapatite/polycaprolactone porous scaffolds in degradation in vitro. Polym. Degrad. Stab. 95(2), 207–213 (2010)CrossRefGoogle Scholar
  177. Wang, G.-H., Zhao, Y.-Z., Tan, J., Zhu, S.-H., Zhou, K.-C.: Arginine functionalized hydroxyapatite nanoparticles and its bioactivity for gene delivery. Trans. Nonferrous Metals Soc. China 25(2), 490–496 (2015)CrossRefGoogle Scholar
  178. Wei, G., Ma, P.X.: Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering. Biomaterials 25(19), 4749–4757 (2004)CrossRefGoogle Scholar
  179. Wei, M., Evans, J.H., Bostrom, T., Grøndahl, L.: Synthesis and characterization of hydroxyapatite, fluoride-substituted hydroxyapatite and fluorapatite. J. Mater. Sci.0020Mater. Med. 14(4), 311–320 (2003)CrossRefGoogle Scholar
  180. Wei, T., Liu, J., Ma, H., Cheng, Q., Huang, Y., Zhao, J., Huo, S., Xue, X., Liang, Z., Liang, X.-J.: Functionalized nanoscale micelles improve drug delivery for cancer therapy in vitro and in vivo. Nano Lett. 13(6), 2528–2534 (2013)CrossRefGoogle Scholar
  181. Wei, T., Chen, C., Liu, J., Liu, C., Posocco, P., Liu, X., Cheng, Q., Huo, S., Liang, Z., Fermeglia, M., Pricl, S., Liang, X.-J., Rocchi, P., Peng, L.: Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance. Proc. Natl. Acad. Sci. 112(10), 2978–2983 (2015)CrossRefGoogle Scholar
  182. Wu, Y., Xia, L., Zhou, Y., Ma, W., Zhang, N., Chang, J., Lin, K., Xu, Y., Jiang, X.: Evaluation of osteogenesis and angiogenesis of icariin loaded on micro/nano hybrid structured hydroxyapatite granules as a local drug delivery system for femoral defect repair. J. Mater. Chem. B 3(24), 4871–4883 (2015)CrossRefGoogle Scholar
  183. Xie, C.-M., Lu, X., Wang, K.-F., Meng, F.-Z., Jiang, O., Zhang, H.-P., Zhi, W., Fang, L.-M.: Silver nanoparticles and growth factors incorporated hydroxyapatite coatings on metallic implant surfaces for enhancement of osteoinductivity and antibacterial properties. ACS Appl. Mater. Interfaces 6(11), 8580–8589 (2014)CrossRefGoogle Scholar
  184. Xie, C., Lu, X., Wang, K., Yuan, H., Fang, L., Zheng, X., Chan, C., Ren, F., Zhao, C.: Pulse electrochemical driven rapid layer-by-layer assembly of polydopamine and hydroxyapatite nanofilms via alternative redox in situ synthesis for bone regeneration. ACS Biomater. Sci. Eng. 2(6), 920–928 (2016)CrossRefGoogle Scholar
  185. Xiong, H., Du, S., Ni, J., Zhou, J., Yao, J.: Mitochondria and nuclei dual-targeted heterogeneous hydroxyapatite nanoparticles for enhancing therapeutic efficacy of doxorubicin. Biomaterials 94, 70–83 (2016)CrossRefGoogle Scholar
  186. Xiong, Z.-C., Yang, Z.-Y., Zhu, Y.-J., Chen, F.-F., Zhang, Y.-G., Yang, R.L.: Ultralong hydroxyapatite nanowires-based paper co-loaded with silver nanoparticles and antibiotic for long-term antibacterial benefit (2017). 1944–8252 (Electronic)Google Scholar
  187. Yan, L., Xiang, Y., Yu, J., Wang, Y., Cui, W.: Fabrication of antibacterial and antiwear hydroxyapatite coatings via in situ chitosan-mediated pulse electrochemical deposition. ACS Appl. Mater. Interfaces 9(5), 5023–5030 (2017)CrossRefGoogle Scholar
  188. Yang, W., Shen, C., Ji, Q., An, H., Wang, J., Liu, Q., Zhang, Z.: Food storage material silver nanoparticles interfere with DNA replication fidelity and bind with DNA. Nanotechnology 20(8), 085102 (2009)CrossRefGoogle Scholar
  189. Ye, Q., Ohsaki, K., Li, K., Li, D.-J., Zhu, C.-S., Ogawa, T., Tenshin, S., Takano-Yamamoto, T.: Histological reaction to hydroxyapatite in the middle ear of rats. Auris Nasus Larynx 28(2), 131–136 (2001)CrossRefGoogle Scholar
  190. Yih, T.C., Al-Fandi, M.: Engineered nanoparticles as precise drug delivery systems. J. Cell. Biochem. 97(6), 1184–1190 (2006)CrossRefGoogle Scholar
  191. Yoo, H.S., Park, T.G.: Folate-receptor-targeted delivery of doxorubicin nano-aggregates stabilized by doxorubicin–PEG–folate conjugate. J. Control. Release 100(2), 247–256 (2004)CrossRefGoogle Scholar
  192. Yunoki, S., Sugiura, H., Ikoma, T., Kondo, E., Yasuda, K., Tanaka, J.: Effects of increased collagen-matrix density on the mechanical properties andin vivoabsorbability of hydroxyapatite–collagen composites as artificial bone materials. Biomed. Mater. 6(1), 015012 (2011)CrossRefGoogle Scholar
  193. Zhang, H.-B., Zhou, K.-C., Li, Z.-Y., Huang, S.-P.: Plate-like hydroxyapatite nanoparticles synthesized by the hydrothermal method. J. Phys. Chem. Solids 70(1), 243–248 (2009a)CrossRefGoogle Scholar
  194. Zhang, P., Hong, Z., Yu, T., Chen, X., Jing, X.: In vivo mineralization and osteogenesis of nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with poly(l-lactide). Biomaterials 30(1), 58–70 (2009b)CrossRefGoogle Scholar
  195. Zhang, L., Pei, J., Wang, H., Shi, Y., Niu, J., Yuan, F., Huang, H., Zhang, H., Yuan, G.: Facile preparation of poly(lactic acid)/brushite bilayer coating on biodegradable magnesium alloys with multiple functionalities for orthopedic application. ACS Appl. Mater. Interfaces. 9(11), 9437–9448 (2017)CrossRefGoogle Scholar
  196. Zhang, Y., Liu, X., Li, Z., Zhu, S., Yuan, X., Cui, Z., Yang, X., Chu, P.K., Wu, S.: Nano Ag/ZnO-incorporated hydroxyapatite composite coatings: highly effective infection prevention and excellent osteointegration. ACS Appl. Mater. Interfaces 10(1), 1266–1277 (2018)CrossRefGoogle Scholar
  197. Zhao, F., Yin, Y., Lu, W.W., Leong, J.C., Zhang, W., Zhang, J., Zhang, M., Yao, K.: Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds. Biomaterials 23(15), 3227–3234 (2002)CrossRefGoogle Scholar
  198. Zhao, J., Liu, Y., Sun, W.-B., Zhang, H.: Amorphous calcium phosphate and its application in dentistry. Chem. Cent. J. 5(1), 40 (2011)CrossRefGoogle Scholar
  199. Zhao, L., Zhao, W., Liu, Y., Chen, X., Wang, Y.: Nano-hydroxyapatite-derived drug and gene co-delivery system for anti-angiogenesis therapy of breast cancer. Med. Sci. Monit.: Int. Med. J. Exp. Clin. Res. 23, 4723–4732 (2017)CrossRefGoogle Scholar
  200. Zimmerli, W., Lew, P., Waldvogel, F.A.: Pathogenesis of foreign body infection. Evidence for a local granulocyte defect. J. Clin. Investig. 73(4), 1191–1200 (1984)CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Behrad Ghiasi
    • 1
  • Yahya Sefidbakht
    • 1
    • 2
    Email author
  • Maryam Rezaei
    • 3
  1. 1.Protein Research CenterShahid Beheshti University, G.CTehranIran
  2. 2.Nanobiotechnology Laboratory, The Faculty of New Technologies Engineering (NTE)Shahid Beheshti University, G.CTehranIran
  3. 3.Institute of Biochemistry and Biophysics (IBB)Tehran UniversityTehranIran

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