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Review Article

Hydroxyapatite as a biomaterial – a gift that keeps on giving

ORCID Icon, , , , , ORCID Icon, , & ORCID Icon show all
Pages 1035-1062 | Received 04 Jan 2020, Accepted 25 May 2020, Published online: 16 Jun 2020

References

  • Uskoković V. The role of hydroxyl channel in defining selected physicochemical peculiarities exhibited by hydroxyapatite. RSC Adv. 2015;5(46):36614–36633.
  • Uskoković V, Uskoković DP. Nanosized hydroxyapatite and other calcium phosphates: chemistry of formation and application as drug and gene delivery agents. J Biomed Mater Res. 2011;96B(1):152–191.
  • Goto T, Kojima T, Iijima T, et al. Resorption of synthetic porous hydroxyapatite and replacement by newly formed bone. J Orthop Sci. 2001;6(5):444–447.
  • Proussaefs P, Lozada J, Valencia G, et al. Histologic evaluation of a hydroxyapatite onlay bone graft retrieved after 9 years: a clinical report. J Prosthet Dent. 2002;87(5):481–484.
  • Uskoković V. When 1 + 1>2: nanostructured composites for hard tissue engineering applications. Mater Sci Eng C Mater Biol Appl. 2015;57:434–451.
  • Ghiasi B, Sefidbakht Y, Rezaei M. Hydroxyapatite for biomedicine and drug delivery. In: Rahmandoust M, Ayatollahi MR, editors. Nanomaterials for advanced biological applications. Cham: Springer International Publishing; 2019. p 85–120.
  • Ohta K, Tada M, Ninomiya Y, et al. Application of interconnected porous hydroxyapatite ceramic block for onlay block bone grafting in implant treatment: a case report. Exp Ther Med. 2017;14(6):5564–5568.
  • Uskoković V, Desai TA. Phase composition control of calcium phosphate nanoparticles for tunable drug delivery kinetics and treatment of osteomyelitis. I. Preparation and drug release. J Biomed Mater Res A. 2013;101(5):1416–1426.
  • Lelli M, Roveri N, Marzano C, et al. Hydroxyapatite nanocrystals as a smart, pH sensitive, delivery system for kiteplatin. Dalton Trans. 2016;45(33):13187–13195.
  • Uskoković V. Ion-doped hydroxyapatite: an impasse or the road to follow? Ceram Int. 2020;46(8):11443–11465.
  • Zeng S, Zhou R, Zheng X, et al. Mono-dispersed Ba2+-doped Nano-hydroxyapatite conjugated with near-infrared Cu-doped CdS quantum dots for CT/fluorescence bimodal targeting cell imaging. Microchem J. 2017;134:41–48.
  • Li H, Mei L, Liu H, et al. Growth mechanism of surfactant-free size-controlled luminescent hydroxyapatite nanocrystallites. Crystal Growth Design. 2017;17(5):2809–2815.
  • Tian D, Sun J, Zhang L, et al. Selective turn-on detection of low levels of cysteine and homocysteine based on fluorescent hydroxyapatite nanoparticles. Anal Methods. 2018;10(38):4644–4647.
  • Machado TR, Sczancoski JC, Beltrán-Mir H, et al. Structural properties and self-activated photoluminescence emissions in hydroxyapatite with distinct particle shapes. Ceram Int. 2018;44(1):236–245.
  • Ignjatović NL, Mančić L, Vuković M, et al. Rare-earth (Gd3+,Yb3+/Tm3+, Eu3+) co-doped hydroxyapatite as magnetic, up-conversion and down-conversion materials for multimodal imaging. Sci Rep. 2019;9(1):16305
  • Zhao X, Ng S, Heng BC, et al. Cytotoxicity of hydroxyapatite nanoparticles is shape and cell dependent. Arch Toxicol. 2013;87(6):1037–1052.
  • Liu X, Zhao M, Lu J, et al. Cell responses to two kinds of nanohydroxyapatite with different sizes and crystallinities. Int J Nanomedicine. 2012;7:1239–1250.
  • Yuan Y, Liu C, Qian J, et al. Size-mediated cytotoxicity and apoptosis of hydroxyapatite nanoparticles in human hepatoma HepG2 cells. Biomaterials. 2010;31(4):730–740.
  • Ignjatović N, Ajduković Z, Savić V, et al. Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones. J Mater Sci Mater Med. 2013;24(2):343–354.
  • Ignjatović N, Uskoković V, Ajduković Z, et al. Multifunctional hydroxyapatite and poly(D,L-lactide-co-glycolide) nanoparticles for the local delivery of cholecalciferol . Mater Sci Eng C Mater Biol Appl. 2013;33(2):943–950.
  • Molino G, Palmieri MC, Montalbano G, et al. Biomimetic and mesoporous nano-hydroxyapatite for bone tissue application: a short review. Biomed Mater. 2020;15(2):022001
  • Lowe B, Hardy JG, Walsh LJ. Optimizing nanohydroxyapatite nanocomposites for bone tissue engineering. ACS Omega. 2020;5(1):1–9.
  • Levingstone TJ, Herbaj S, Dunne NJ. Calcium phosphate nanoparticles for therapeutic applications in bone regeneration. Nanomaterials. 2019;9(11):1570.
  • Singh G, Singh RP, Jolly SS. Customized hydroxyapatites for bone-tissue engineering and drug delivery applications: a review. J Sol-Gel Sci Technol. 2020;94(3):505–530.
  • Levingstone TJ, Herbaj S, Redmond J, et al. Calcium phosphate nanoparticles-based systems for RNAi delivery: applications in bone tissue regeneration. Nanomaterials. 2020;10(1):146.
  • Albulescu R, Popa A-C, Enciu A-M, et al. Comprehensive in vitro testing of calcium phosphate-based bioceramics with orthopedic and dentistry applications. Materials. 2019;12(22):3704.
  • Arcos D, Vallet-Regí M. Substituted hydroxyapatite coatings of bone implants. J Mater Chem B. 2020;8(9):1781–1800.
  • Su Y, Cockerill I, Zheng Y, et al. Biofunctionalization of metallic implants by calcium phosphate coatings. Bioact Mater. 2019;4:196–206.
  • Priyadarshini B, Rama M, Vijayalakshmi C, et al. Bioactive coating as a surface modification technique for biocompatible metallic implants: a review. J Asian Ceram Soc. 2019;7(4):397–406.
  • Choi G, Choi AH, Evans LA, et al. A review: recent advances in sol-gel-derived hydroxyapatite nanocoatings for clinical applications. J Amer Ceram Soc. 2020;0:1–12.
  • Li T-T, Ling L, Lin M-C, et al. Recent advances in multifunctional hydroxyapatite coating by electrochemical deposition. J Mater Sci. 2020;55(15):6352–6374.
  • Ain Q, Zeeshan M, Khan S, et al. Biomimetic hydroxyapatite as potential polymeric nanocarrier for the treatment of rheumatoid arthritis. J Biomed Mater Res A. 2019;107(12):2595–2600.
  • Pajor K, Pajchel L, Kolmas J. Hydroxyapatite and fluorapatite in conservative dentistry and oral implantology—a review. Materials. 2019;12(17):2683.
  • Jaiswal S, Dubey A, Lahiri D. In Vitro biodegradation and biocompatibility of Mg–HA-based composites for orthopaedic applications: a review. J Indian Inst Sci. 2019;99(3):303–327.
  • Dorozhkin SV. Functionalized calcium orthophosphates (CaPO4) and their biomedical applications. J Mater Chem B. 2019;7(47):7471–7489.
  • Wei G, Gong C, Hu K, et al. Biomimetic hydroxyapatite on graphene supports for biomedical applications: a review. Nanomaterials. 2019;9(10):1435.
  • Zhu Y-J, Lu B-Q. Deformable biomaterials based on ultralong hydroxyapatite nanowires. ACS Biomater Sci Eng. 2019;5(10):4951–4961.
  • Kumar A, Kargozar S, Baino F, et al. Additive manufacturing methods for producing hydroxyapatite and hydroxyapatite-based composite scaffolds: a review. Front Mater. 2019;6(313)
  • Mondal S, Pal U. 3D hydroxyapatite scaffold for bone regeneration and local drug delivery applications. J Drug Delivery Sci Technol. 2019;53:101131.
  • Yokoi T. The development of novel calcium phosphate–polymer composite biomaterials with macro- to nano-level controlled hierarchical structures. J Ceram Soc Japan. 2019;127(10):715–721.
  • Christy PN, Basha SK, Kumari VS, et al. Biopolymeric nanocomposite scaffolds for bone tissue engineering applications–A review. J Drug Delivery Sci Technol. 2020;55:101452.
  • Nonoyama T. Robust hydrogel–bioceramics composite and its osteoconductive properties. Polym J. 2020;86:1–8.
  • Xu X, Chen X, Li J. Natural protein bioinspired materials for regeneration of hard tissues. J Mater Chem B. 2020;8(11):2199–2215.
  • Rasheed T, Nabeel F, Raza A, et al. Biomimetic nanostructures/cues as drug delivery systems: a review. Mater Today Chem. 2019;13:147–157.
  • Ahirwar H, Zhou Y, Mahapatra C, et al. Materials for orthopedic bioimplants: modulating degradation and surface modification using integrated nanomaterials. Coatings. 2020;10(3):264.
  • Šupová M. The significance and utilisation of biomimetic and bioinspired strategies in the field of biomedical material engineering: the case of calcium phosphat—protein template constructs. Materials. 2020;13(2):327.
  • Velu R, Calais T, Jayakumar A, et al. A comprehensive review on bio-nanomaterials for medical implants and feasibility studies on fabrication of such implants by additive manufacturing technique. Materials. 2019;13(1):92.
  • Beheshtizadeh N, Lotfibakhshaiesh N, Pazhouhnia Z, et al. A review of 3D bio-printing for bone and skin tissue engineering: a commercial approach. J Mater Sci. 2020;55(9):3729–3749.
  • Zafar MJ, Zhu D, Zhang Z. 3D printing of bioceramics for bone tissue engineering. Materials. 2019;12(20):3361.
  • Masaeli R, Zandsalimi K, Rasoulianboroujeni M, et al. Challenges in three-dimensional printing of bone substitutes. Tissue Eng Part B Rev. 2019;25(5):387–397.
  • Wang S-Y, Hu H-Z, Qing X-C, et al. Recent advances of drug delivery nanocarriers in osteosarcoma treatment. J Cancer. 2020;11(1):69–82.
  • D’Souza M, Macdonald NA, Gendreau JL, et al. Graft materials and biologics for spinal interbody fusion. Biomedicines. 2019;7(4):75.
  • Manatunga DC, Godakanda VU, de Silva RM, et al. Recent developments in the use of organic-inorganic nanohybrids for drug delivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2020;12(3):e1605.
  • Sanz-Herrera JA, Reina-Romo E. Continuum modeling and simulation in bone tissue engineering. Appl Sci. 2019;9(18):3674.
  • Kelly DC, Raftery RM, Curtin CM, et al. Scaffold-based delivery of nucleic acid therapeutics for enhanced bone and cartilage repair. J Orthop Res. 2019;37(8):1671–1680.
  • UNOS. Data.
  • Liu Y, Thantrakul C, Kan S, et al. Feasibility of using high-contrast grating as a point-of-care sensor for therapeutic drug monitoring of immunosuppressants. IEEE J Transl Eng Health Med. 2020;8:1–6.
  • Fernandez de Grado G, Keller L, Idoux-Gillet Y, et al. Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management. J Tissue Eng. 2018;9:2041731418776819.
  • Winkler T, Sass FA, Duda GN, et al. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: the unsolved challenge. Bone Joint Res. 2018;7(3):232–243.
  • Gattuso J-P, Frankignoulle M, Bourge I, et al. Effect of calcium carbonate saturation of seawater on coral calcification. Global Planet Change. 1998;18(1–2):37–46.
  • Ozin GA. Nanochemistry: synthesis in diminishing dimensions. Adv Mater. 1992;4(10):612–649.
  • Dorozhkin SV. Nanodimensional and nanocrystalline apatites and other calcium orthophosphates in biomedical engineering, biology and medicine. Materials. 2009;2(4):1975–2045.
  • Dorozhkin SV. A detailed history of calcium orthophosphates from 1770s till 1950. Mater Sci Eng C Mater Biol Appl. 2013;33(6):3085–3110.
  • Wu V, Uskoković V. Waiting for Aπαταω: 250 years later. Found Sci. 2019;24(4):617–640.
  • Kattimani VS, Kondaka S, Lingamaneni KP. Hydroxyapatite–past, present, and future in bone regeneration. Bone Tissue Regen Insights. 2016;7:BTRI.S36138.
  • Sultan M. Hydroxyapatite/polyurethane composites as promising biomaterials. Chem Pap. 2018;72(10):2375–2395.
  • Piskin E. Biodegradable polymers as biomaterials. J Biomater Sci Polym Ed. 1995;6(9):775–795.
  • Ji Y, Ghosh K, Shu XZ, et al. Electrospun three-dimensional hyaluronic acid nanofibrous scaffolds. Biomaterials. 2006;27(20):3782–3792.
  • Farokhi M, Mottaghitalab F, Samani S, et al. Silk fibroin/hydroxyapatite composites for bone tissue engineering. Biotechnol Adv. 2018;36(1):68–91.
  • Park J-Y, Yang C, Jung I-H, et al. Regeneration of rabbit calvarial defects using cells-implanted nano-hydroxyapatite coated silk scaffolds. Biomater Res. 2015;19(1):7
  • Yu P, Bao R-Y, Shi X-J, et al. Self-assembled high-strength hydroxyapatite/graphene oxide/chitosan composite hydrogel for bone tissue engineering. Carbohydr Polym. 2017;155:507–515.
  • Sharma C, Dinda AK, Potdar PD, et al. Fabrication and characterization of novel nano-biocomposite scaffold of chitosan-gelatin-alginate-hydroxyapatite for bone tissue engineering. Mater Sci Eng C Mater Biol Appl. 2016;64:416–427.
  • Heidari F, Bahrololoom ME, Vashaee D, et al. In situ preparation of iron oxide nanoparticles in natural hydroxyapatite/chitosan matrix for bone tissue engineering application. Ceram Int. 2015;41(2):3094–3100.
  • Kulanthaivel S, Roy B, Agarwal T, et al. Cobalt doped proangiogenic hydroxyapatite for bone tissue engineering application. Mater Sci Eng C Mater Biol Appl. 2016;58:648–658.
  • Peng S, Feng P, Wu P, et al. Graphene oxide as an interface phase between polyetheretherketone and hydroxyapatite for tissue engineering scaffolds. Sci Rep. 2017;7:46604.
  • Kim MH, Kim BS, Lee J, et al. Silk fibroin/hydroxyapatite composite hydrogel induced by gamma-ray irradiation for bone tissue engineering. Biomater Res. 2017;21(1):12.
  • Lin L, Hao R, Xiong W, et al. Quantitative analyses of the effect of silk fibroin/nano-hydroxyapatite composites on osteogenic differentiation of MG-63 human osteosarcoma cells. J Biosci Bioeng. 2015;119(5):591–595.
  • Ahmed MK, Mansour SF, Al-Wafi R, et al. Tuning the mechanical, microstructural, and cell adhesion properties of electrospun ε-polycaprolactone microfibers by doping selenium-containing carbonated hydroxyapatite as a reinforcing agent with magnesium ions. J Mater Sci. 2019;54(23):14524–14544.
  • Nie W, Peng C, Zhou X, et al. Three-dimensional porous scaffold by self-assembly of reduced graphene oxide and nano-hydroxyapatite composites for bone tissue engineering. Carbon. 2017;116:325–337.
  • Hickey DJ, Ercan B, Sun L, et al. Adding MgO nanoparticles to hydroxyapatite-PLLA nanocomposites for improved bone tissue engineering applications. Acta Biomater. 2015;14:175–184.
  • Schmid J, Schwarz S, Fischer M, et al. A laser-cutting-based manufacturing process for the generation of three-dimensional scaffolds for tissue engineering using Polycaprolactone/Hydroxyapatite composite polymer. J Tissue Eng. 2019;10:2041731419859157.
  • Akindoyo JO, Beg MDH, Ghazali S, et al. Impact modified PLA-hydroxyapatite composites—Thermo-mechanical properties. Compos Pt A Appl Sci Manuf. 2018;107:326–333.
  • Lee WD, Gawri R, Pilliar RM, et al. Sol gel-derived hydroxyapatite films over porous calcium polyphosphate substrates for improved tissue engineering of osteochondral-like constructs. Acta Biomater. 2017;62:352–361.
  • Lee J, Kim J, Bae M, et al. Development of poly(ɛ-caprolactone) scaffold loaded with simvastatin and beta-cyclodextrin modified hydroxyapatite inclusion complex for bone tissue engineering. Polymers. 2016;8(2):49.
  • Quinlan E, López-Noriega A, Thompson E, et al. Development of collagen-hydroxyapatite scaffolds incorporating PLGA and alginate microparticles for the controlled delivery of rhBMP-2 for bone tissue engineering. J Control Release. 2015;198:71–79.
  • Lei Y, Xu Z, Ke Q, et al. Strontium hydroxyapatite/chitosan nanohybrid scaffolds with enhanced osteoinductivity for bone tissue engineering. Mater Sci Eng C Mater Biol Appl. 2017;72:134–142.
  • Barneo-Caragol C, Martínez-Morillo E, Rodríguez-González S, et al. Strontium and its role in preeclampsia. J Trace Elem Med Biol. 2018;47:37–44.
  • Strontium ranelate discontinued. Drug Ther Bull. 2017. 55(8):93–94.
  • Khalid S, Calderon-Larrañaga S, Hawley S, et al. Comparative anti-fracture effectiveness of different oral anti-osteoporosis therapies based on "real-world" data: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database. Clin Epidemiol. 2018;10:1417–1431.
  • Driessens FCM, De Maeyer EAP, Fernández E, et al. Amorphous calcium phosphate cements and their transformation into calcium deficient hydroxyapatite. Bioceramics. 1996;9:231–234.
  • Ghosh S, Wu V, Pernal S, et al. Self-setting calcium phosphate cements with tunable antibiotic release rates for advanced antimicrobial applications. ACS Appl Mater Interfaces. 2016;8(12):7691–7708.
  • Chow LC, Eanes ED. Octacalcium phosphate. Basel (Switzerland): Karger Medical and Scientific Publishers; 2001.
  • Rau JV, Fadeeva IV, Fomin AS, et al. Sic parvis magna: manganese-substituted tricalcium phosphate and its biophysical properties. ACS Biomater Sci Eng. 2019;5(12):6632–6644.
  • Uskoković V, Graziani V, Wu VM, et al. Gold is for the mistress, silver for the maid: enhanced mechanical properties, osteoinduction and antibacterial activity due to iron doping of tricalcium phosphate bone cements. Mater Sci Eng C Mater Biol Appl. 2019;94:798–810.
  • Rau JV, Wu VM, Graziani V, et al. The bone building blues: self-hardening copper-doped calcium phosphate cement and its in vitro assessment against mammalian cells and bacteria. Mater Sci Eng C Mater Biol Appl. 2017;79:270–279.
  • Dorozhkin SV. Calcium orthophosphate cements and concretes. Materials. 2009;2(1):221–291.
  • Uskoković V, Ghosh S, Wu VM. Antimicrobial hydroxyapatite-gelatin-silica composite pastes with tunable setting properties. J Mater Chem B. 2017;5(30):6065–6080.
  • Uswatta SP, Okeke IU, Jayasuriya AC. Injectable porous nano-hydroxyapatite/chitosan/tripolyphosphate scaffolds with improved compressive strength for bone regeneration. Mater Sci Eng C. 2016;69:505–512.
  • Cox SC, Thornby JA, Gibbons GJ, et al. 3D printing of porous hydroxyapatite scaffolds intended for use in bone tissue engineering applications. Mater Sci Eng C Mater Biol Appl. 2015;47:237–247.
  • Sinlapabodin S, Amornsudthiwat P, Damrongsakkul S, et al. An axial distribution of seeding, proliferation, and osteogenic differentiation of MC3T3-E1 cells and rat bone marrow-derived mesenchymal stem cells across a 3D Thai silk fibroin/gelatin/hydroxyapatite scaffold in a perfusion bioreactor. Mater Sci Eng C Mater Biol Appl. 2016;58:960–970.
  • Qi XN, Mou ZL, Zhang J, et al. Preparation of chitosan/silk fibroin/hydroxyapatite porous scaffold and its characteristics in comparison to bi-component scaffolds. J Biomed Mater Res A. 2014;102(2):366–372.
  • Yang W, Both SK, Zuo Y, et al. Biological evaluation of porous aliphatic polyurethane/hydroxyapatite composite scaffolds for bone tissue engineering. J Biomed Mater Res A. 2015;103(7):2251–2259.
  • Ahmed MK, Mansour SF, Al-Wafi R, et al. Gold as a dopant in selenium-containing carbonated hydroxyapatite fillers of nanofibrous ε-polycaprolactone scaffolds for tissue engineering. Int J Pharm. 2020;577:118950.
  • Ong JL, Chan DC. Hydroxyapatite and their use as coatings in dental implants: a review. Crit Rev Biomed Eng. 2000;28(5-6): 667–707.
  • Szcześ A, Hołysz L, Chibowski E. Synthesis of hydroxyapatite for biomedical applications. Adv Colloid Interface Sci. 2017;249:321–330.
  • Haider A, Haider S, Han SS, et al. Recent advances in the synthesis, functionalization and biomedical applications of hydroxyapatite: a review. RSC Adv. 2017;7(13):7442–7458.
  • Alagarsamy K, Vishwakarma V, Kaliaraj GS, et al. Implant application of bioactive nano-hydroxyapatite powders—a comparative study. Mater Res Express. 2018;5(1):015405.
  • Senthil R, Vedakumari SW, Sastry TP. Hydroxyapatite and demineralized bone matrix from marine food waste–a possible bone implant. AJMSP. 2018;3(1):1.
  • Mazaheri M, Haghighatzadeh M, Zahedi A, et al. Effect of a novel sintering process on mechanical properties of hydroxyapatite ceramics. J Alloys Compd. 2009;471(1-2):180–184.
  • Zaccaria L, Tharakan SJ, Altermatt S. Hydroxyapatite ceramic implants for cranioplasty in children: a single-center experience. Childs Nerv Syst. 2017;33(2):343–348.
  • Lim H-P, Park S-W, Yun K-D, et al. Hydroxyapatite Coating on TiO2 Nanotube by Sol–Gel Method for Implant Applications. J Nanosci Nanotechnol. 2018;18(2):1403–1405.
  • Kumar RM, Kuntal KK, Singh S, et al. Electrophoretic deposition of hydroxyapatite coating on Mg–3Zn alloy for orthopaedic application. Surf Coat Technol. 2016;287:82–92.
  • Ciobanu G, Harja M. Cerium-doped hydroxyapatite/collagen coatings on titanium for bone implants. Ceram Int. 2019;45(2):2852–2857.
  • Huang Y, Xu Z, Zhang X, et al. Nanotube-formed Ti substrates coated with silicate/silver co-doped hydroxyapatite as prospective materials for bone implants. J Alloys Compd. 2017;697:182–199.
  • Tao Z-S, Zhou W-S, He X-W, et al. A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats. Mater Sci Eng C Mater Biol Appl. 2016;62:226–232.
  • Wijesinghe W, Mantilaka M, Senarathna KC, et al. Preparation of bone-implants by coating hydroxyapatite nanoparticles on self-formed titanium dioxide thin-layers on titanium metal surfaces. Mater Sci Eng C Mater Biol Appl. 2016;63:172–184.
  • Li Y, Yang W, Li X, et al. Improving osteointegration and osteogenesis of three-dimensional porous Ti6Al4V scaffolds by polydopamine-assisted biomimetic hydroxyapatite coating. ACS Appl Mater Interfaces. 2015;7(10):5715–5724.
  • Gryshkov O, Klyui NI, Temchenko VP, et al. Porous biomorphic silicon carbide ceramics coated with hydroxyapatite as prospective materials for bone implants. Mater Sci Eng C Mater Biol Appl. 2016;68:143–152.
  • Guimond-Lischer S, Ren Q, Braissant O, et al. Vacuum plasma sprayed coatings using ionic silver doped hydroxyapatite powder to prevent bacterial infection of bone implants. Biointerphases. 2016;11(2):011012.
  • Xie C-M, Lu X, Wang K-F, et al. Silver nanoparticles and growth factors incorporated hydroxyapatite coatings on metallic implant surfaces for enhancement of osteoinductivity and antibacterial properties. ACS Appl Mater Interfaces. 2014;6(11):8580–8589.
  • Yu W-Z, Zhang Y, Liu X, et al. Synergistic antibacterial activity of multi components in lysozyme/chitosan/silver/hydroxyapatite hybrid coating. Mater Des. 2018;139:351–362.
  • Zhang Y, Liu X, Li Z, et al. Nano Ag/ZnO-incorporated hydroxyapatite composite coatings: highly effective infection prevention and excellent osteointegration. ACS Appl Mater Interfaces. 2018;10(1):1266–1277.
  • Tao Z-S, Zhou W-S, Qiang Z, et al. Intermittent administration of human parathyroid hormone (1-34) increases fixation of strontium-doped hydroxyapatite coating titanium implants via electrochemical deposition in ovariectomized rat femur . J Biomater Appl. 2016;30(7):952–960.
  • Laonapakul T, Rakngarm Nimkerdphol A, Otsuka Y, et al. Failure behavior of plasma-sprayed HAp coating on commercially pure titanium substrate in simulated body fluid (SBF) under bending load. J Mech Behav Biomed Mater. 2012;15:153–166.
  • He G, Guo B, Wang H, et al. Surface characterization and osteoblast response to a functionally graded hydroxyapatite/fluoro-hydroxyapatite/titanium oxide coating on titanium surface by sol-gel method. Cell Prolif. 2014;47(3):258–266.
  • Singh S, Kumar RM, Kuntal KK, et al. Sol–gel derived hydroxyapatite coating on Mg-3Zn alloy for orthopedic application. JOM. 2015;67(4):702–712.
  • Nelea V, Ristoscu C, Chiritescu C, et al. Pulsed laser deposition of hydroxyapatite thin films on Ti-5Al-2.5 Fe substrates with and without buffer layers. Appl Surf Sci. 2000;168(1-4):127–131.
  • Levingstone TJ, Ardhaoui M, Benyounis K, et al. Plasma sprayed hydroxyapatite coatings: understanding process relationships using design of experiment analysis. Surf Coat Technol. 2015;283:29–36.
  • Hao J, Kuroda S, Ohya K, et al. Enhanced osteoblast and osteoclast responses to a thin film sputtered hydroxyapatite coating. J Mater Sci Mater Med. 2011;22(6):1489–1499.
  • Rammelt S, Schulze E, Bernhardt R, et al. Coating of titanium implants with type-I collagen. J Orthop Res. 2004;22(5):1025–1034.
  • Pham MH, Haugen HJ, Rinna A, et al. Hydrofluoric acid treatment of titanium surfaces enhances the proliferation of human gingival fibroblasts. J Tissue Eng. 2019;10:2041731419828950.
  • Murugan N, Murugan C, Sundramoorthy AK. In vitro and in vivo characterization of mineralized hydroxyapatite/polycaprolactone-graphene oxide based bioactive multifunctional coating on Ti alloy for bone implant applications. Arab J Chem. 11(6):959–969.
  • Murugan N, Murugan C, Sundramoorthy AK. In vitro and in vivo characterization of mineralized hydroxyapatite/polycaprolactone-graphene oxide based bioactive multifunctional coating on Ti alloy for bone implant applications. Arab J Chem. 2018;11(6):959–969.
  • Alghamdi HS, Bosco R, Both SK, et al. Synergistic effects of bisphosphonate and calcium phosphate nanoparticles on peri-implant bone responses in osteoporotic rats. Biomaterials. 2014;35(21):5482–5490.
  • Bosco R, Iafisco M, Tampieri A, et al. Hydroxyapatite nanocrystals functionalized with alendronate as bioactive components for bone implant coatings to decrease osteoclastic activity. Appl Surf Sci. 2015;328:516–524.
  • Prosolov KA, Belyavskaya OA, Rau JV, et al. Deposition of polycrystalline zinc substituted hydroxyapatite coatings with a columnar structure by RF magnetron sputtering: role of in-situ substrate heating. J Phys Conf Ser. 2018;1115:032077.
  • Prosolov KA, Belyavskaya OA, Muehle U, et al. Thin bioactive Zn substituted hydroxyapatite coating deposited on ultrafine-grained titanium substrate: structure analysis. Front Mater. 2018;5(3). DOI:10.3389/fmats.2018.00003
  • Prosolov KA, Belyavskaya OA, Linders J, et al. Glancing angle deposition of Zn-doped calcium phosphate coatings by RF magnetron sputtering. Coatings. 2019;9(4):220.
  • Sedelnikova MB, Komarova EG, Sharkeev YP, et al. Modification of titanium surface via Ag-, Sr- and Si-containing micro-arc calcium phosphate coating. Bioact Mater. 2019;4:224–235.
  • Otsuka Y, Kawaguchi H, Mutoh Y. Cyclic delamination behavior of plasma-sprayed hydroxyapatite coating on Ti-6Al-4V substrates in simulated body fluid. Mater Sci Eng C Mater Biol Appl. 2016;67:533–541.
  • Uskokovic V. Nanostructured platforms for the sustained and local delivery of antibiotics in the treatment of osteomyelitis. Crit Rev Ther Drug Carrier Syst. 2015;32(1):1–59.
  • Ciocilteu M-V, Mocanu AG, Mocanu A, et al. Hydroxyapatite-ciprofloxacin delivery system: synthesis, characterisation and antibacterial activity. Acta Pharm. 2018;68(2):129–144.
  • Munir MU, Ihsan A, Sarwar Y, et al. Hollow mesoporous hydroxyapatite nanostructures; smart nanocarriers with high drug loading and controlled releasing features. Int J Pharm. 2018;544(1):112–120.
  • Kumar GS, Govindan R, Girija E. In situ synthesis, characterization and in vitro studies of ciprofloxacin loaded hydroxyapatite nanoparticles for the treatment of osteomyelitis. J Mater Chem B. 2014;2(31):5052–5060.
  • Amaro Martins VC, Goissis G. Nonstoichiometric hydroxyapatite-anionic collagen composite as support for the double sustained release of gentamicin and norfloxacin/ciprofloxacin . Artif Organs. 2000;24(3):224–230.
  • Xiong Z-C, Yang Z-Y, Zhu Y-J, et al. Ultralong hydroxyapatite nanowires-based paper co-loaded with silver nanoparticles and antibiotic for long-term antibacterial benefit. ACS Appl Mater Interfaces. 2017;9(27):22212–22222.
  • Sangeetha K, Ashok M, Girija EK, et al. Strontium and ciprofloxacin modified hydroxyapatites as functional grafts for bone prostheses. Ceram Int. 2018;44(12):13782–13789.
  • Butini ME, Cabric S, Trampuz A, et al. In vitro anti-biofilm activity of a biphasic gentamicin-loaded calcium sulfate/hydroxyapatite bone graft substitute. Colloids Surf B Biointerfaces. 2018;161:252–260.
  • Madhumathi K, Kumar TS. Regenerative potential and anti-bacterial activity of tetracycline loaded apatitic nanocarriers for the treatment of periodontitis. Biomed Mater. 2014;9(3):035002.
  • Soriano-Souza CA, Rossi AL, Mavropoulos E, et al. Chlorhexidine-loaded hydroxyapatite microspheres as an antimicrobial delivery system and its effect on in vivo osteo-conductive properties. J Mater Sci Mater Med. 2015;26(4):166.
  • Tsai S-W, Huang S-S, Yu W-X, et al. Fabrication and characteristics of porous hydroxyapatite-CaO composite nanofibers for biomedical applications. Nanomaterials. 2018;8(8):570.
  • Tsai S-W, Yu W-X, Hwang P-A, et al. Fabrication and characterization of strontium-substituted hydroxyapatite-CaO-CaCO3 nanofibers with a mesoporous structure as drug delivery carriers. Pharmaceutics. 2018;10(4):179.
  • Ren B, Chen X, Du S, et al. Injectable polysaccharide hydrogel embedded with hydroxyapatite and calcium carbonate for drug delivery and bone tissue engineering. Int J Biol Macromol. 2018;118(Pt A):1257–1266.
  • Ramírez-Agudelo R, Scheuermann K, Gala-García A, et al. Hybrid nanofibers based on poly-caprolactone/gelatin/hydroxyapatite nanoparticles-loaded Doxycycline: effective anti-tumoral and antibacterial activity. Mater Sci Eng C Mater Biol Appl. 2018;83:25–34.
  • Ding L, Zhang P, Wang X, et al. Effect of doxycycline-treated hydroxyapatite surface on bone apposition: a histomophometric study in murine maxillae. Dent Mater J. 2018;37(1):130–138.
  • Sörensen JH, Lilja M, Sörensen TC, et al. Biomechanical and antibacterial properties of Tobramycin loaded hydroxyapatite coated fixation pins. J Biomed Mater Res Part B Appl Biomater. 2014;102(7):1381–1392.
  • Ionita D, Bajenaru-Georgescu D, Totea G, et al. Activity of vancomycin release from bioinspired coatings of hydroxyapatite or TiO2 nanotubes. Int J Pharm. 2017;517(1-2):296–302.
  • Zihayat B, Khodadadi A, Torabi M, et al. Wound healing activity of sheep’s bladder extracellular matrix in diabetic rats. Biomed Eng Appl Basis Commun. 2018;30(02):1850015.
  • Cao Z, Jiang D, Yan L, et al. In vitro and in vivo drug release and antibacterial properties of the novel vancomycin-loaded bone-like hydroxyapatite/poly amino acid scaffold. Int J Nanomedicine. 2017;12:1841–1851.
  • Karr JC. Lower-extremity osteomyelitis treatment using calcium sulfate/hydroxyapatite bone void filler with antibiotics seven-year retrospective study . J Am Podiatr Med Assoc. 2018;108(3):210–214.
  • Singh RP, Singh G, Singh H. Sub-micrometric mesoporous strontium substituted hydroxyapatite particles for sustained delivery of vancomycin drug. J Aust Ceram Soc. 2019;55(2):405–410.
  • Giacomini D, Torricelli P, Gentilomi GA, et al. Monocyclic β-lactams loaded on hydroxyapatite: new biomaterials with enhanced antibacterial activity against resistant strains. Sci Rep. 2017;7(1):2712
  • Zomorodian A, Santos C, Carmezim M, et al. In-vitro” corrosion behaviour of the magnesium alloy with Al and Zn (AZ31) protected with a biodegradable polycaprolactone coating loaded with hydroxyapatite and cephalexin. Electrochim Acta. 2015;179:431–440.
  • Wan T, Stylios GK, Giannoudi M, et al. Investigating a new drug delivery nano composite membrane system based on PVA/PCL and PVA/HA (PEG) for the controlled release of biopharmaceuticals for bone infections. Injury. 2015;46:S39–S43.
  • Rădulescu D, Grumezescu V, Andronescu E, et al. Biocompatible cephalosporin-hydroxyapatite-poly (lactic-co-glycolic acid)-coatings fabricated by MAPLE technique for the prevention of bone implant associated infections. Appl Surf Sci. 2016;374:387–396.
  • Queiroz A, Santos J, Monteiro F, et al. Adsorption and release studies of sodium ampicillin from hydroxyapatite and glass-reinforced hydroxyapatite composites. Biomaterials. 2001;22(11):1393–1400.
  • Pradid J, Keawwatana W, Boonyang U, et al. Biological properties and enzymatic degradation studies of clindamycin-loaded PLA/HAp microspheres prepared from crocodile bones. Polym Bull. 2017;74(12):5181–5194.
  • Gonzalez G, Sagarzazu A, Cordova A, et al. Comparative study of two silica mesoporous materials (SBA-16 and SBA-15) modified with a hydroxyapatite layer for clindamycin controlled delivery. Microporous Mesoporous Mater. 2018;256:251–265.
  • Zamoume O, Thibault S, Regnié G, et al. Macroporous calcium phosphate ceramic implants for sustained drug delivery. Mater Sci Eng C. 2011;31(7):1352–1356.
  • Deepak A, Goyal AK, Rath G. Development and characterization of novel medicated nanofiber for the treatment of periodontitis. AAPS PharmSciTech. 2018;19(8):3687–3697.
  • Ardhani R, Setyaningsih , Hafiyyah OA, Ana ID. Preparation of carbonated apatite membrane as metronidazole delivery system for periodontal application. Key Eng Mater. 2016;696:250–258.
  • Deshmukh K, Shaik MM, Ramanan SR, et al. Self-activated fluorescent hydroxyapatite nanoparticles: a promising agent for bioimaging and biolabeling. ACS Biomater Sci Eng. 2016;2(8):1257–1264.
  • Predoi D, Iconaru SL, Buton N, et al. Antimicrobial activity of new materials based on lavender and basil essential oils and hydroxyapatite. Nanomaterials. 2018;8(5):291.
  • Mueller B, Treccani L, Rezwan K. Antibacterial active open-porous hydroxyapatite/lysozyme scaffolds suitable as bone graft and depot for localised drug delivery. J Biomater Appl. 2017;31(8):1123–1134.
  • Chen X, Deng C, Tang S, et al. Mitochondria-dependent apoptosis induced by nanoscale hydroxyapatite in human gastric cancer SGC-7901 cells. Biol Pharm Bull. 2007;30(1):128–132.
  • Xu J, Xu P, Li Z, et al. Oxidative stress and apoptosis induced by hydroxyapatite nanoparticles in C6 cells. J Biomed Mater Res A. 2012;100(3):738–745.
  • Li B, Guo B, Fan H, et al. Preparation of nano-hydroxyapatite particles with different morphology and their response to highly malignant melanoma cells in vitro. Appl Surf Sci. 2008;255(2):357–360.
  • Uskoković V, Iyer MA, Wu VM. One ion to rule them all: combined antibacterial, osteoinductive and anticancer properties of selenite-incorporated hydroxyapatite. J Mater Chem B. 2017;5(7):1430–1445.
  • Ignjatović NL, Sakač M, Kuzminac I, et al. Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells. J Mater Chem B. 2018;6(43):6957–6968.
  • Ignjatović NL, Penov-Gaši KM, Wu VM, et al. Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. Colloid Surf B. 2016;148:629–639.
  • Adamiano A, Wu VM, Carella F, et al. Magnetic calcium phosphates nanocomposites for the intracellular hyperthermia of cancers of bone and brain. Nanomedicine (Lond). 2019;14(10):1267–1289.
  • Han Y, Li S, Cao X, et al. Different inhibitory effect and mechanism of hydroxyapatite nanoparticles on normal cells and cancer cells in vitro and in vivo. Sci Rep. 2014;4:7134.
  • Sun Y, Chen Y, Ma X, et al. Mitochondria-targeted hydroxyapatite nanoparticles for selective growth inhibition of lung cancer in vitro and in vivo. ACS Appl Mater Interfaces. 2016;8(39):25680–25690.
  • Tang W, Yuan Y, Liu C, et al. Differential cytotoxicity and particle action of hydroxyapatite nanoparticles in human cancer cells. Nanomedicine (Lond). 2014;9(3):397–412.
  • Chen L, Mccrate JM, Lee JC, et al. The role of surface charge on the uptake and biocompatibility of hydroxyapatite nanoparticles with osteoblast cells. Nanotechnology. 2011;22(10):105708.
  • Zhao X, Heng BC, Xiong S, et al. In vitro assessment of cellular responses to rod-shaped hydroxyapatite nanoparticles of varying lengths and surface areas. Nanotoxicology. 2011;5(2):182–194.
  • Li G, Ye L, Pan J, et al. Antitumoural hydroxyapatite nanoparticles‐mediated hepatoma‐targeted trans‐arterial embolization gene therapy: in vitro and in vivo studies. Liver Int. 2012;32(6):998–1007.
  • Bauer IW, Li S-P, Han Y-C, et al. Internalization of hydroxyapatite nanoparticles in liver cancer cells. J Mater Sci: Mater Med. 2008;19(3):1091–1095.
  • Jiang W, Kim BY, Rutka JT, et al. Nanoparticle-mediated cellular response is size-dependent. Nat Nanotechnol. 2008;3(3):145–150.
  • Wang L, Zhou G, Liu H, et al. Nano-hydroxyapatite particles induce apoptosis on MC3T3-E1 cells and tissue cells in SD rats. Nanoscale. 2012;4(9):2894–2899.
  • Tay CY, Fang W, Setyawati MI, et al. Nano-hydroxyapatite and nano-titanium dioxide exhibit different subcellular distribution and apoptotic profile in human oral epithelium. ACS Appl Mater Interfaces. 2014;6(9):6248–6256.
  • Gómez-Morales J, Iafisco M, Delgado-López JM, et al. Progress on the preparation of nanocrystalline apatites and surface characterization: overview of fundamental and applied aspects. Prog Cryst Growth Charact Mater. 2013;59(1):1–46.
  • Wu VM, Tang S, Uskoković V. Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: the antibacterial effect. ACS Appl Mater Interfaces. 2018;10(40):34013–34028.
  • Yanhua W, Hao H, Li Y, et al. Selenium-substituted hydroxyapatite nanoparticles and their in vivo antitumor effect on hepatocellular carcinoma. Colloids Surf B Biointerfaces. 2016;140:297–306.
  • Xiong H, Du S, Ni J, et al. Mitochondria and nuclei dual-targeted heterogeneous hydroxyapatite nanoparticles for enhancing therapeutic efficacy of doxorubicin. Biomaterials. 2016;94:70–83.
  • Kundu B, Ghosh D, Sinha MK, et al. Doxorubicin-intercalated nano-hydroxyapatite drug-delivery system for liver cancer: an animal model. Ceram Int. 2013;39(8):9557–9566.
  • Gerweck LE. Tumor pH: implications for treatment and novel drug design. Semin Radiat Oncol. 1998;8(3):176–182.
  • Sun W, Fan J, Wang S, et al. Biodegradable drug-loaded hydroxyapatite nanotherapeutic agent for targeted drug release in tumors. ACS Appl Mater Interfaces. 2018;10(9):7832–7840.
  • Li D, Huang X, Wu Y, et al. Preparation of pH-responsive mesoporous hydroxyapatite nanoparticles for intracellular controlled release of an anticancer drug. Biomater Sci. 2016;4(2):272–280.
  • Maeda H, Tsukigawa K, Fang J. A Retrospective 30 years after discovery of the enhanced permeability and retention effect of solid tumors: next-generation chemotherapeutics and photodynamic therapy-problems, solutions, and prospects. Microcirculation. 2016;23(3):173–182.
  • Rastegar R, Akbari Javar H, Khoobi M, et al. and others. Evaluation of a novel biocompatible magnetic nanomedicine based on beta-cyclodextrin, loaded doxorubicin-curcumin for overcoming chemoresistance in breast cancer. Artif Cells Nanomed Biotechnol. 2018;46(sup2):207–216.
  • Graham FL, van der Eb AJ. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973;52(2):456–467.
  • Sokolova V, Epple M. Inorganic nanoparticles as carriers of nucleic acids into cells. Angew Chem Int Ed Engl. 2008;47(8):1382–1395.
  • Ramamoorth M, Narvekar A. Non viral vectors in gene therapy- an overview. J Clin Diagn Res. 2015;9(1):GE01–GE06.
  • Bisht S, Bhakta G, Mitra S, et al. pDNA loaded calcium phosphate nanoparticles: highly efficient non-viral vector for gene delivery. Int J Pharm. 2005;288(1):157–168.
  • Lee D, Upadhye K, Kumta PN. Nano-sized calcium phosphate (CaP) carriers for non-viral gene deilvery. Mater Sci Eng B. 2012;177(3):289–302.
  • Xu H, Wei D, Gai X, et al. Amine functionalised hydroxyapatite nanoparticles for anti-angiogenesis gene therapy of breast cancer. Micro Nano Lett. 2016;11(8):416–419.
  • Welzel T, Radtke I, Meyer-Zaika W, et al. Transfection of cells with custom-made calcium phosphate nanoparticles coated with DNA. J Mater Chem. 2004;14(14):2213–2217.
  • Wu G-J, Zhou L-Z, Wang K-W, et al. Hydroxylapatite nanorods: an efficient and promising carrier for gene transfection. J Colloid Interface Sci. 2010;345(2):427–432.
  • Zhu S, Huang B, Zhou K, et al. Hydroxyapatite nanoparticles as a novel gene carrier. J Nanopart Res. 2004;6(2/3):307–311.
  • Olton D, Li J, Wilson ME, et al. Nanostructured calcium phosphates (NanoCaPs) for non-viral gene delivery: influence of the synthesis parameters on transfection efficiency. Biomaterials. 2007;28(6):1267–1279.
  • Khan MA, Wu VM, Ghosh S, et al. Gene delivery using calcium phosphate nanoparticles: optimization of the transfection process and the effects of citrate and poly(l-lysine) as additives. J Colloid Interface Sci. 2016;471:48–58.
  • Cheang T-Y, Lei Y-Y, Zhang Z-Q, et al. Graphene oxide-hydroxyapatite nanocomposites effectively deliver HSV-TK suicide gene to inhibit human breast cancer growth . J Biomater Appl. 2018;33(2):216–226.
  • Hanifi A, Fathi MH, Mir Mohammad Sadeghi H, et al. Mg2+ substituted calcium phosphate nano particles synthesis for non viral gene delivery application. J Mater Sci Mater Med. 2010;21(8):2393–2401.
  • Klesing J, Chernousova S, Epple M. Freeze-dried cationic calcium phosphate nanorods as versatile carriers of nucleic acids (DNA, siRNA). J Mater Chem. 2012;22(1):199–204.
  • Wang G-h, Zhao Y-z, Tan J, et al. Arginine functionalized hydroxyapatite nanoparticles and its bioactivity for gene delivery. Trans Nonferrous Met Soc China. 2015;25(2):490–496.
  • Komuro H, Sasano T, Horiuchi N, et al. The effect of glucose modification of hydroxyapatite nanoparticles on gene delivery. J Biomed Mater Res A. 2019;107(1):61–66.
  • Lee SY, Jeon SI, Jung S, et al. Targeted multimodal imaging modalities. Adv Drug Deliv Rev. 2014;76:60–78.
  • Norek M, Peters JA. MRI contrast agents based on dysprosium or holmium. Prog Nucl Magn Reson Spectrosc. 2011;59(1):64–82.
  • Xi D, Dong S, Meng X, et al. Gold nanoparticles as computerized tomography (CT) contrast agents. RSC Adv Colloid Interface Sci. 2012;2:12515–12524.
  • Lusic H, Grinstaff MW. X-ray-computed tomography contrast agents. Chem Rev. 2013;113(3):1641–1666.
  • Ametamey SM, Honer M, Schubiger PA. Molecular imaging with PET. Chem Rev. 2008;108(5):1501–1516.
  • Li Z, Conti PS. Radiopharmaceutical chemistry for positron emission tomography. Adv Drug Deliv Rev. 2010;62(11):1031–1051.
  • Wades TW, Weisman GR, Anderson CJ. Coordinating radiometals of copper, gallium, indium, yttrium and zirconium for PET and SPECT imaging of disease. Chem Rev. 2010;110:2858–2902.
  • Gobin AL, Halas NJ, James WD, et al. Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. Nano Lett. 2007;7(7):1929–1934. 1934.
  • AF F. Optical coherence tomography-development, principles, applications. Z Med Phys. 2009;20:251–276.
  • Pansare VJ, Hejazi S, Faenza WJ, et al. Review of long-wavelength optical and NIR imaging materials: ontrast agents, fluorophores, and multifunctional nano carriers. Chem Mater. 2012;24(5):812–827.
  • Harvey CJ, Blomley MJ, Eckersley RJ, et al. Developments in ultrasound contrast media. Eur Radiol. 2001;11(4):675–689.
  • Guo C, Jin Y, Dai Z. Multifunctional ultrasound contrast agents for imaging guided photothermal therapy. Bioconjug Chem. 2014;25(5):840–854.
  • Lu WHQ, Ku G, Wen X, et al. Photoacoustic imaging of living mouse brain vasculature using hollow gold nanospheres. Biomaterials. 2010;31(9):2617–2626.
  • Kherlopian AR, Song T, Duan Q, et al. 4. A review of imaging techniques for systems biology. BMC Syst Biol. 2008;2:74.
  • Sharma P, Brown S, Walter G, et al. Nanoparticles for bioimaging. Adv Colloid Interface Sci. 2006;123-126:471–485.
  • Soo Choi1 H, Frangioni1 JV. Nanoparticles for biomedical imaging: fundamentals of clinical translation. Mol Imaging. 2010;9(6):291–310.
  • Ntziachristos V. Fluorescence molecular imaging. Annu Rev Biomed Eng. 2006;8(1):1–33.
  • Liu H, Chen F, Xi P, et al. Biocompatible fluorescent hydroxyapatite: synthesis and live cell imaging applications. J Phys Chem C. 2011;115(38):18538–18544.
  • Syamchand SS, Sony G. Multifunctional hydroxyapatite nanoparticles for drug delivery and multimodal molecular imaging. Microchim Acta. 2015;182(9-10):1567–1589.
  • Uskoković V, Tang S, Nikolić MG, et al. Calcium phosphate nanoparticles as intrinsic inorganic antimicrobials: in search of the key particle property. Biointerphases. 2019;14(3):031001.
  • Erhan I, Altınoǧlu † TJR, Kaiser JM §, et al., Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer. Appl Surf Sci. 2017;419:188–196.
  • Kester M, Fox T, Sharma A, et al. Calcium phosphate nanocomposite particles for in vitro imaging and encapsulated chemotherapeutic drug delivery to cancer cells. Nano Lett. 2008;8(12):4116–4121.
  • Mondéjar SP, Kovtun A, Epple M. Lanthanide-doped calcium phosphate nanoparticles with high internal crystallinity and with a shell of DNA as fluorescent probes in cell experiments. J Mater Chem. 2007;17(39):4153.
  • Li M, Oh J, Xie X, et al. Simultaneous molecular and hypoxia imaging of brain tumors in vivo using spectroscopic photoacoustic tomography. Proc Ieee. 2008;96(3):481–489.
  • de Araujo TS, Macedo ZS, de Oliveira PASC, et al. Production and characterization of pure and Cr3+-doped hydroxyapatite for biomedical applications as fluorescent probes. J Mater Sci. 2007;42(7):2236–2243.
  • Jagannathan RK. Eu3+ luminescence: a spectral probe in M5(PO4)3X apatites (M = Ca or Sr; X = F-, Cl-, Br- or OH). J Phys Condens Matter. 1995;7(44).
  • Graeve OA, Kanakala R, Madadi A, et al. Luminescence variations in hydroxyapatites doped with Eu2+ and Eu3+ ions. Biomaterials. 2010;31(15):4259–4267.
  • Rakovan J, Reeder RJ. ntracrystalline rare earth element distributions in apatite: surface structural influences on zoning during growth. Geochim Cosmochim Acta. 1996;60(22):4435–4445.
  • Reisfeld R, Gaft M, Boulon G, et al. Laser-induced luminescence of rare-earth elements in natural fluor-apatites. J Lumin. 1996;69(5-6):343–353.
  • Mayer I, Layani JD, Givan A, et al. La ions in precipitated hydroxyapatites. J Inorg Biochem. 1999;73(4):221–226.
  • Martin P, Carlot G, Chevarier A, et al. Mechanisms involved in thermal diffusion of rare earth elements in apatite. J Nucl Mater. 1999;275(3):268–276.
  • Doat A, Fanjul M, Pellé F, et al. Europium-doped bioapatite: a new photostable biological probe, internalizable by human cells. Biomaterials. 2003;24(19):3365–3371.
  • Doat A, Pellé F, Gardant N, et al. Synthesis of luminescent bioapatite nanoparticles for utilization as a biological probe. J Solid State Chem. 2004;177(4-5):1179–1187.
  • Doat A, Pellé F, Lebugle A. Europium-doped calcium pyrophosphates : allotropic forms and photoluminescent properties. J Solid State Chem. 2005;178(7):2354–2362.
  • Ciobanu CS, Iconaru SL, Le Coustumer P, et al. Antibacterial activity of silver-doped hydroxyapatite nanoparticles against gram-positive and gram-negative bacteria. Nanoscale Res Lett. 2012;7(1):324.
  • Ciobanu CM, Andronescu E, Stan MS, et al. Biocompatibility study of europium doped crystalline hydroxyapatite bioceramics. Dig J Nanomater Bios. 2011;6(4):1639–1647.
  • Capobianco JA, Proulx PP, Raspa N. Laser-excited fluorescence spectroscopy and crystal field analysis of europium (III)-doped cordierite glass. Chem Phys Lett. 1989;160(5-6):591–596.
  • Lavin VB, Jayasankar CK, Martin IR, et al. On the local structure of Eu3+ ions in oxifluoride glasses. Comparison with fluoride and oxide glasses. J Chem Phys. 2001;23:10935–10944.
  • Zambelli M, Abril M, Lavín V, et al. Fluorescence line narrowing spectroscopy of Eu3+ in a niobium tellurite glass. Phys Non-Crystalline Solids. 2004;345-346(15):386–390.
  • Kushida T. Site-selective fluorescence spectroscopy of Eu3+ and Sm2+ ions in glass. J Lumin. 2002;100(1–4):73–88.
  • Doweidar H. Density–structure correlations in Na2O–CaO–P2O5–SiO2 bioactive glasses. J Non-Cryst Solids. 2009;355(9):577–580.
  • Iconaru S-L, Motelica-Heino M, Predoi D. Study on europium-doped hydroxyapatite nanoparticles by fourier transform infrared spectroscopy and their antimicrobial properties. J Spectro. 2013;2013:1–10.
  • Weerasuriya DRK, Wijesinghe W, Rajapakse R. Encapsulation of anticancer drug copper bis(8-hydroxyquinoline) in hydroxyapatite for pH-sensitive targeted delivery and slow release. Mater Sci Eng C Mater Biol Appl. 2017;71:206–213.
  • Matsuya T, Otsuka Y, Tagaya M, et al. Formation of stacked luminescent complex of 8-hydroxyquinoline molecules on hydroxyapatite coating by using cold isostatic pressing. Mater Sci Eng. 2016;58:127–132. (1873-0191 (Electronic)).
  • Neacsu IA, Stoica AE, Vasile BS, et al. Luminescent hydroxyapatite doped with rare earth elements for biomedical applications. Nanomaterials (Basel, Switzerland). 2019;9(2):239.
  • Matsuya T, Otsuka Y, Tagaya M, et al. Formation of stacked luminescent complex of 8-hydroxyquinoline molecules on hydroxyapatite coating by using cold isostatic pressing. Mater Sci Eng C Mater Biol Appl. 2016;58:127–132.
  • Li ZLZ, Yin M, Yang X, et al. Aptamer-capped multifunctional mesoporous strontium hydroxyapatite nanovehicle for cancer-cell-responsive drug delivery and imaging. Biomacromolecules. 2012;13(12):4257–4263.
  • Stanic V, Dimitrijević S, Antonovic DG, et al. Synthesis of fluorine substituted hydroxyapatite nanopowders and application of the central composite design for determination of its antimicrobial effects. Appl Surf Sci. 2014;290:346–352.
  • Yang Y-H, Liu C-H, Liang Y-H, et al. Hollow mesoporous hydroxyapatite nanoparticles (hmHANPs) with enhanced drug loading and pH-responsive release properties for intracellular drug delivery. J Mater Chem B. 2013;1(19):2447–2450.
  • Mao L, Liu X, Liu M, et al. Surface grafting of zwitterionic polymers onto dye doped AIE-active luminescent silica nanoparticles through surface-initiated ATRP for biological imaging applications. Appl Surf Sci. 2017;419:188–196.
  • Byrne JD, Betancourt T, Brannon-Peppas L, 60Active targeting schemes for nanoparticle system in cancer therapeutics. Adv Drug Deliv Rev. 2008;60(15):1615–1626.
  • Yu MK, Park J, Jon S. Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy. Theranostics. 2012;2(1):3–44.
  • Sandhöfer B, Meckel M, Delgado-López JM, et al. Synthesis and preliminary in vivo evaluation of well-dispersed biomimetic nanocrystalline apatites labeled with positron emission tomographic imaging agents. ACS Appl Mater Interfaces. 2015;7(19):10623–10633.
  • Adamiano A, Iafisco M, Sandri M, et al. On the use of superparamagnetic hydroxyapatite nanoparticles as an agent for magnetic and nuclear in vivo imaging. Acta Biomater. 2018;73:458–469.
  • Zhao H, Wu C, Gao D, et al. Antitumor effect by hydroxyapatite nanospheres: activation of mitochondria-dependent apoptosis and negative regulation of phosphatidylinositol-3-kinase/protein kinase B pathway. ACS Nano. 2018;12(8):7838–7854.
  • Wang X, Li X, Ito A, et al. Rod-shaped and fluorine-substituted hydroxyapatite free of molecular immunopotentiators stimulates anti-cancer immunity in vivo. Chem Commun (Camb). 2016;52(44):7078–7081.
  • Tomoaia G, Pop L-B, Petean I, et al. Significance of surface structure on orthopedic materials. Mater. Plast. 2012;49(1):48–54.
  • Jung F, Braune S. Thrombogenicity and hemocompatibility of biomaterials. Biointerphases. 2015;11(2):029601.
  • Hoffman M, Monroe DM. IIIA cell-based model of hemostasis. Thromb Haemost. 2001;85(6):958–965.
  • McGuigan AP, Sefton MV. The influence of biomaterials on endothelial cell thrombogenicity. Biomaterials. 2007;28(16):2547–2571.
  • Yan Y, Gause KT, Kamphuis MM, et al. Differential roles of the protein corona in the cellular uptake of nanoporous polymer particles by monocyte and macrophage cell lines. ACS Nano. 2013;7(12):10960–10970.
  • Chen X, Wang Q, Shen J, et al. Adsorption of Leucine-Rich Amelogenin Protein on Hydroxyapatite (001) Surface through − COO-Claws. J Phys Chem C. 2007;111(3):1284–1290.
  • Dong X, Wang Q, Wu T, et al. Understanding adsorption-desorption dynamics of BMP-2 on hydroxyapatite (001) surface. Biophys J. 2007;93(3):750–759.
  • Shen J-W, Wu T, Wang Q, et al. Molecular simulation of protein adsorption and desorption on hydroxyapatite surfaces. Biomaterials. 2008;29(5):513–532.
  • Docter D, Strieth S, Westmeier D, et al. No king without a crown-impact of the nanomaterial-protein corona on nanobiomedicine. Nanomedicine (Lond). 2015;10(3):503–519.
  • Mayer A, Vadon M, Rinner B, et al. The role of nanoparticle size in hemocompatibility. Toxicology. 2009;258(2-3):139–147.
  • Wu Z, Haixia L, Wei Y, et al. Hydroxyapatite/silk fibroin composite biomimetic scaffold for dental pulp repair. Bioinspir Biomim Nan. 2019;8(4):231–238.
  • Bhattacharjee A, Gupta A, Verma M, et al. Site-specific antibacterial efficacy and cyto/hemo-compatibility of zinc substituted hydroxyapatite. Ceram Int. 2019;45(9):12225–12233.
  • Ooi C-H, Ling YP, Abdullah WZ, et al. evaluation and in vitro hemocompatibility study on nanoporous hydroxyapatite. J Mater Sci Mater Med. 2019;30(4):44.
  • Chen X, Feng L, Peng R, et al. Studies on nano-particle sols of hydroxyaptite and titanium dioxide for haemo-compatibility. Wei sheng yan jiu=. J hygiene res.. 2002;31(3):197–199.
  • Han Y, Wang X, Dai H, et al. Nanosize and surface charge effects of hydroxyapatite nanoparticles on red blood cell suspensions. ACS Appl Mater Interfaces. 2012;4(9):4616–4622.
  • Liu X, Sun J. Potential proinflammatory effects of hydroxyapatite nanoparticles on endothelial cells in a monocyte–endothelial cell coculture model. Int J Nanomed. 2014;9:1261–1273.
  • Katanasaka Y, Ida T, Asai T, et al. Antiangiogenic cancer therapy using tumor vasculature-targeted liposomes encapsulating 3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one, SU5416. Cancer Lett. 2008;270(2):260–268.
  • Puvvada N, Panigrahi PK, Pathak A. Room temperature synthesis of highly hemocompatible hydroxyapatite, study of their physical properties and spectroscopic correlation of particle size. Nanoscale. 2010;2(12):2631–2638.
  • Santos C, Turiel S, Sousa Gomes P, et al. Vascular biosafety of commercial hydroxyapatite particles: discrepancy between blood compatibility assays and endothelial cell behavior. J Nanobiotechnology. 2018;16(1):27.
  • Turkez H, Yousef MI, Sönmez E, et al. Evaluation of cytotoxic, oxidative stress and genotoxic responses of hydroxyapatite nanoparticles on human blood cells. J Appl Toxicol. 2014;34(4):373–379.
  • Sun J, Xie G. Tissue distribution of intravenously administrated hydroxyapatite nanoparticles labeled with 125I. J Nanosci Nanotechnol. 2011;11(12):10996–11000.
  • Ignjatović N, Vranješ Djurić S, Mitić Ž, et al. Investigating an organ-targeting platform based on hydroxyapatite nanoparticles using a novel in situ method of radioactive 125Iodine labeling. Mater Sci Eng C Mater Biol Appl. 2014;43:439–446.
  • Ding T, Xue Y, Lu H, et al. Effect of particle size of hydroxyapatite nanoparticles on its biocompatibility. IEEE Trans Nanobioscience. 2012;11(4):336–340.
  • Remya NS, Syama S, Gayathri V, et al. An in vitro study on the interaction of hydroxyapatite nanoparticles and bone marrow mesenchymal stem cells for assessing the toxicological behaviour. Colloids Surf B Biointerfaces. 2014;117:389–397.
  • Ramis J, Coelho C, Córdoba A, et al. Safety assessment of nano-hydroxyapatite as an oral care ingredient according to the EU cosmetics regulation. Cosmetics. 2018;5(3):53.
  • Gustavsson J, Ginebra MP, Engel E, et al. Ion reactivity of calcium-deficient hydroxyapatite in standard cell culture media. Acta Biomater. 2011;7(12):4242–4252.
  • Gustavsson J, Ginebra MP, Planell J, et al. Osteoblast-like cellular response to dynamic changes in the ionic extracellular environment produced by calcium-deficient hydroxyapatite. J Mater Sci Mater Med. 2012;23(10):2509–2520.
  • Entering the era of nanoscience: time to be so small Vuk Uskokovíc. J Biomed Nanotechnol. 2013;9(9):1441–1470.
  • Jones CF, Grainger DW. In vitro assessments of nanomaterial toxicity. Adv Drug Deliv Rev. 2009;61(6):438–456.
  • Kang K-S, Trosko JE. Stem cells in toxicology: fundamental biology and practical considerations. Toxicol Sci. 2011;120(Supplement 1):S269–S289.
  • Uskoković V. Nanotechnologies: what we do not know. Technol Soc. 2007;29(1):43–61.

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