Skip to main content
SpringerLink
Log in

Impact of TiO2 nanomaterials with different morphologies and their calcium phosphate composites on hemostasis and immunocompatibility

  • Published:
Bulletin of Materials Science Aims and scope Submit manuscript

Abstract

The increasing use of TiO2 nanomaterials (TiNMs) in bone tissue engineering raises concerns about their biocompatibility. To date, majority of biological testing was focused on the cytotoxicity of TiO2 nanoparticles and their composites. However, evaluation of immunocompatibility and effects on hemostasis is crucial for successful clinical applications of bone regeneration materials. Such data are scarce for TiNMs. To fill this gap, this study aimed to investigate impact of TiNMs with different morphologies and their composites with calcium deficient hydroxyapatite (CaDHA/TiNMs) on hemostasis, as well as the cell viability and inflammatory response of Jurkat T cells. Four different TiNMs, nanoparticles (TiNPs), nanoplates (TiNPls), nanotubes (TiNTs), nanowires (TiNWs), and their composites with CaDHA were studied. Among investigated materials, the least effect was observed for CaDHA. Effect on plasma coagulation was observed only for TiNPs, which shortened the prothrombin time. All TiNMs affected global hemostasis, especially the elongated TiNWs. Coating TiNMs with CaDHA resulted in a less pronounced effect compared to TiNMs. No significant effect on the viability of Jurkat T cells was observed for TiNMs, while composites increased it. Analysis of the expression of pro-inflammatory (IL-6, IL-8 and TNFα) and anti-inflammatory (IL-10) cytokines indicated inflammatory potential of investigated materials. Among TiNMs, TiNWs had the most pronounced pro-inflammatory effect, while CaDHA/TiNTs and CaDHA/TiNWs showed the most pronounced effect among composites. The obtained results confirm the potential of investigated materials for biomedical applications. However, further studies are needed to establish a more precise relationship between the materials’ physico-chemical properties and their biological effects, thus ensuring their safe application.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Sahare P, Alvarez P G, Yanez J M S, Bárcenas J G L, Chakraborty S, Paul S et al 2022 Beilstein J. Nanotechnol. 13 201

    Article  CAS  Google Scholar 

  2. Wu S, Weng Z, Liu X, Yeung K W K and Chu Paul K 2014 Adv. Funct. Mater. 24 5464

    Article  CAS  Google Scholar 

  3. Bonelli B, Esposito S and Freyria F S 2017 In: Janus M (ed) Titanium Dioxide (InTech) p 68884

  4. Yin Z F, Wu L, Yang H G and Su Y H 2013 Phys. Chem. Chem. Phys. 15 4844

    Article  Google Scholar 

  5. Lee K, Mazare A and Schmuki P 2014 Chem. Rev. 114 9385

    Article  CAS  Google Scholar 

  6. Wang X, Li Z, Shi J and Yu Y 2014 Chem. Rev. 114 9346

    Article  CAS  Google Scholar 

  7. Rajh T, Dimitrijevic N M, Bissonnette M, Koritarov T and Konda V 2014 Chem. Rev. 114 10177

    Article  CAS  Google Scholar 

  8. De Marchi L, Coppola F, Soares A M, Pretti C, Monserrat J M, Della Torre C et al 2019 Environ. Res. 178 108683

    Article  Google Scholar 

  9. Chen X and Mao S S 2007 Chem. Rev. 107 2891

    Article  CAS  Google Scholar 

  10. Bai J and Zhou B 2014 Chem. Rev. 114 10131

    Article  CAS  Google Scholar 

  11. Bai Y, Mora-Seró I, De Angelis F, Bisquert J and Wang P 2014 Chem. Rev. 114 10095

    Article  CAS  Google Scholar 

  12. Bhattacharya K, Kiliç G, Costa P M and Fadeel B 2017 Nanotoxicology 11 809

    CAS  Google Scholar 

  13. Ye G, Bao F, Zhang X, Song Z, Liao Y, Fei Y et al 2020 Nanomedicine 15 1995

    Article  CAS  Google Scholar 

  14. Manivasagam V K and Popat K C 2020 ACS Omega 5 8108

    Article  CAS  Google Scholar 

  15. Jayakumar R, Ramachandran R, Divyarani V V, Chennazhi K P, Tamura H and Nair S V 2011 Int. J. Biol. Macromol. 48 336

    Article  CAS  Google Scholar 

  16. Zhu Q, Li X, Fan Z, Xu Y, Niu H, Li C et al 2018 Mater. Sci. Eng. C 85 79

    Article  CAS  Google Scholar 

  17. Boskey A L 2013 In: Ratner B, Hoffman A, Schoen F, Lemons J (eds.) Biomaterials Science: An introduction to materials in medicine (Elsevier), p 307

  18. Pandit A, Planell J and Navarro M 2013 In: Ratner B, Hoffman A, Schoen F and Lemons J (eds.) Biomaterials Science: An introduction to materials in medicine (Elsevier), p 120

  19. Joseph Nathanael A, Mangalaraj D, Chen P C and Ponpandian N 2010 Compos. Sci. Technol. 70 419

    Article  CAS  Google Scholar 

  20. Pushpakanth S, Srinivasan B, Sreedhar B and Sastry T P 2008 Mater. Chem. Phys. 107 492

    Article  CAS  Google Scholar 

  21. Enayati-Jazi M, Solati-Hashjin M, Nemati A and Bakhshi F 2012 Superlattices Microstruct. 51 877

    Article  CAS  Google Scholar 

  22. Nath S, Tripathi R and Basu B 2009 Mater. Sci. Eng. C 29 97

    Article  CAS  Google Scholar 

  23. Oktar F N 2006 Mater. Lett. 60 2207

    Article  CAS  Google Scholar 

  24. Que W, Khor K A, Xu J L and Yu L G 2008 J. Eur. Ceram. Soc. 28 3083

    Article  CAS  Google Scholar 

  25. Salarian M, Xu W Z, Wang Z, Sham T-K and Charpentier P A 2014 ACS Appl. Mater. Interfaces 6 16918

    Article  CAS  Google Scholar 

  26. Giannakopoulou T, Todorova N, Romanos G, Vaimakis T, Dillert R, Bahnemann D et al 2012 Mater. Sci. Eng. B 177 1046

    Article  CAS  Google Scholar 

  27. Milella E 2001 Biomaterials 22 1425

    Article  CAS  Google Scholar 

  28. Erceg I, Selmani A, Gajović A, Panžić I, Iveković D, Faraguna F et al 2020 Colloids Surf. A 593 124615

    Article  CAS  Google Scholar 

  29. Erceg I, Selmani A, Gajović A, Radatović B, Šegota S, Ćurlin M et al 2021 Nanomaterials 11 1523

    Article  CAS  Google Scholar 

  30. García-Rodríguez A, Vila L, Cortés C, Hernández A and Marcos R 2018 Part. Fibre Toxicol. 15 33

    Article  Google Scholar 

  31. Ilić K, Selmani A, Milić M, Glavan T M, Zapletal E, Ćurlin M et al 2020 J. Nanopart. Res. 22 71

    Article  Google Scholar 

  32. Musial J, Krakowiak R, Mlynarczyk D T, Goslinski T and Stanisz B J 2020 Nanomaterials 4 1110

    Article  Google Scholar 

  33. Richter J W, Shull G M, Fountain J H, Guo Z, Musselman L P, Fiumera A C et al 2018 Nanotoxicology 12 390

    Article  CAS  Google Scholar 

  34. Liu S, Xu L, Zhang T, Ren G and Yang Z 2010 Toxicology 267 172

    Article  CAS  Google Scholar 

  35. Park E-J, Yi J, Chung K-H, Ryu D-Y, Choi J and Park K 2008 Toxicol. Lett. 180 222

    Article  CAS  Google Scholar 

  36. Venkataprasanna K S, Prakash J, Anusuya T and Devanand Venkatasubbu G 2021 J. Sol-Gel Sci. Technol. 99 565

    Article  CAS  Google Scholar 

  37. Ipach I, Schäfer R, Mittag F, Leichtle C, Wolf P and Kluba T 2012 BMC Musculoskelet. Disord. 13 159

    Article  Google Scholar 

  38. Temiz M, Dayi E and Saruhan N 2018 BioMed Res. Int. 4121639

  39. Han X, Kuang Q, Jin M, Xie Z and Zheng L 2009 J. Am. Chem. Soc. 131 3152

    Article  CAS  Google Scholar 

  40. Sofianou M V, Trapalis C, Psycharis V, Boukos N, Vaimakis T, Yu J et al 2012 Environ. Sci. Pollut. Res. 19 3719

    Article  CAS  Google Scholar 

  41. Selmani A, Špadina M, Plodinec M, Delač Marion I, Willinger M G, Lützenkirchen J et al 2015 J. Phys. Chem. C 119 19729

    Article  CAS  Google Scholar 

  42. Simak J and De Paoli S 2017 Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 9 1448

    Article  Google Scholar 

  43. Lancé M D 2015 Thrombosis J 13 1

    Article  Google Scholar 

  44. Abdalla A O, Kiaii S, Hansson L, Rossmann E D, Jeddi-Tehrani M, Shokri F et al 2003 Scand. J. Immunol. 58 601–606

    Article  CAS  Google Scholar 

  45. Fan J, Nishanian P, Breen E C, McDonald M and Fahey J L 1998 Clin. Diagn. Lab. Immunol. 5 335–340

    Article  CAS  Google Scholar 

  46. Livak K J and Schmittgen T D 2001 Methods 25 402

    Article  CAS  Google Scholar 

  47. Dorozhkin S V (ed) 2012 Calcium Orthophosphates: Applications in Nature, Biology, and Medicine (Singapore: Pan Stanford)

  48. Liou S C, Chen S Y, Lee H Y and Bow J S 2004 Biomaterials 25 189

    Article  CAS  Google Scholar 

  49. Buljan Meić I, Kontrec J, Domazet Jurašin D, Njegić Džakula B, Stajner L, Lyons D M et al 2017 Cryst. Growth Design 17 1103

    Article  Google Scholar 

  50. Elimelech M 1998 Particle deposition and aggregation: measurement, modelling, and simulation (Butterworth-Heinemann: Woburn)

  51. Akaighe N, Depner S W, Banerjee S, Sharma V K and Sohn M 2012 Sci. Total Environ. 441 277–289

    Article  CAS  Google Scholar 

  52. Chen Q and Thouas G (eds) 2015 Biomaterials: A Basic Introduction (Boca Raton: CRC Press)

    Google Scholar 

  53. Fröhlich E 2016 Curr. Med. Chem. 23 408

    Article  Google Scholar 

  54. Milić M, Vuković B, Barbir R, Pem B, Milić M, Šerić V et al 2020 Platelets 32 651

    Article  Google Scholar 

  55. Kaneko A, Hirai S, Tamada Y and Kuzuya T 2009 Sen-i Gakkaishi 65 97

    Article  CAS  Google Scholar 

  56. Takemoto S, Kusudo Y, Tsuru K, Hayakawa S, Osaka A and Takashima S 2004 J. Biomed. Mater. Res. 69A 544

    Article  CAS  Google Scholar 

  57. Wang X, Luo Y, Yang Y, Zheng B, Yan F, Wei F et al 2018 J. Mater. Chem. B 6 8204

    Article  CAS  Google Scholar 

  58. Shiu H T, Goss B, Lutton C, Crawford R and Xiao Y 2014 J. Mater. Chem. B 2 3009

    Article  CAS  Google Scholar 

  59. Akay O M 2018 Clin. Appl. Thromb. Hemost. 24 850

    Article  Google Scholar 

  60. Yang Y, Lai Y, Zhang Q, Wu K, Zhang L, Lin C et al 2010 Coll. Surf. B 79 309

    Article  CAS  Google Scholar 

  61. Smith B S, Yoriya S, Grissom L, Grimes C A and Popat K C 2010 J. Biomed. Mater. Res. 95A 350

    Article  CAS  Google Scholar 

  62. Maitz M F, Pham M-T, Wieser E and Tsyganov I 2003 J. Biomater. Appl. 17 303

    Article  CAS  Google Scholar 

  63. Yoshihara H, Ozeki K, Masuzawa T and Aoki H 2008 Appl. Surf. Sci. 255 2869

    Article  CAS  Google Scholar 

  64. Zhao H, Ma L, Gao C, Wang J and Shen J 2009 Mater. Sci. Eng. C 29 836

    Article  CAS  Google Scholar 

  65. Luo Y H, Chang L W and Lin P 2015 BioMed Res. Int. 143720

  66. Sukwong P, Kongseng S, Chaicherd S, Yoovathaworn K, Tubtimkuna S and Pissuwan D 2017 IET Nanobiotechnol. 11 759

    Article  Google Scholar 

  67. May S, Hirsch C, Rippl A, Bürkle A and Wick P 2022 Nanomaterials 12 220

    Article  CAS  Google Scholar 

  68. Sharkeev Y P, Komarova E G, Chebodaeva V V, Sedelnikova M B, Zakharenko A M, Golokhvast K S et al A 2021 Materials 14 3693

    Article  CAS  Google Scholar 

  69. Litvinova L S, Khaziakhmatova O G, Shupletsova V V, Yurova K A, Malashchenko V V, Shunkin E O et al 2020 Materials 13 4307

    Article  CAS  Google Scholar 

  70. Baht G S, Vi L and Alman B A 2018 Curr. Osteoporos. Rep. 16 138

    Article  Google Scholar 

  71. Maruyama M, Rhee C, Utsunomiya T, Zhang N, Ueno M, Yao Z et al 2020 Front. Endocrinol. 11 386

    Article  Google Scholar 

  72. Jones K S 2008 Semin. Immunol. 20 130

    Article  CAS  Google Scholar 

  73. Jämsen E, Kouri V-P, Ainola M, Goodman S B, Nordström D C, Eklund K K et al 2017 J. Biomed. Mater. Res. 105 454

    Article  Google Scholar 

  74. Di Benedetto A, Gigante I, Colucci S and Grano M 2013 Clin Dev Immunol. A 503754

  75. Xie Z, Tang S, Ye G, Wang P, Li J, Liu W et al 2018 Stem. Cell. Res. Ther. 9 13

    Article  CAS  Google Scholar 

  76. Landgraeber S, Jäger M, Jacobs J J and Hallab N J 2014 Mediat. Inflamm. 185150

  77. Ito H 2011 Mod. Rheumatol. 21 113

    Article  CAS  Google Scholar 

  78. Kindle L, Rothe L, Kriss M, Osdoby P and Collin-Osdoby P 2005 J. Bone Miner. Res. 21 193

    Article  Google Scholar 

  79. Nakahama K 2010 Cell. Mol. Life Sci. 67 4001

    Article  CAS  Google Scholar 

  80. Ghali O, Chauveau C, Hardouin P, Broux O and Devedjian J-C 2010 J. Bone Miner. Res. 25 1616

    Article  CAS  Google Scholar 

  81. Trindade M C D, Lind M, Nakashima Y, Sun D, Goodman S B, Schurman D J et al 2001 Biomaterials 22 2067

    Article  CAS  Google Scholar 

  82. Park E-J, Shim H-W, Lee G-H, Kim J-H and Kim D-W 2013 Arch. Toxicol. 87 1219

    Article  CAS  Google Scholar 

  83. Dalal A, Pawar V, McAllister K, Weaver C and Hallab N J 2012 J. Biomed. Mater. Res. 100A 2147

    Article  CAS  Google Scholar 

  84. Warme B A, Epstein N J, Trindade M C D, Miyanishi K, Ma T, Saket R R et al 2004 J. Biomed. Mater. Res. 71B 360

    Article  CAS  Google Scholar 

  85. Kutikhin A G, Velikanova E A, Mukhamadiyarov R A, Glushkova T V, Borisov V V, Matveeva V G et al 2016 Sci. Rep. 6 27255

  86. Wang X, Luo Y, Masci P P, Crawford R and Xiao Y 2016 PLoS ONE 6 35645

    CAS  Google Scholar 

  87. Velard F, Braux J, Amedee J and Laquerriere P 2013 Acta Biomater. 9 4956

    Article  CAS  Google Scholar 

  88. Lange T, Schilling A F, Peters F, Mujas J, Wicklein D and Amling M 2011 Biomaterials 32 4067

    Article  CAS  Google Scholar 

  89. Fernandes K R, Zhang Y, Magri A M P, Renno A C M and van den Beucken J J J P 2017 ACS Biomater. Sci. Eng. 3 3318

    Article  CAS  Google Scholar 

  90. Hamlet S and Ivanovski S 2011 Acta Biomater. 7 2345

    Article  CAS  Google Scholar 

  91. Kreller T, Sahm F, Bader R, Boccaccini A R, Jonitz-Heincke A and Detsch R 2021 Materials 14 3516

    Article  CAS  Google Scholar 

  92. Rydén L, Molnar D, Esposito M, Johansson A, Suska F, Palmquist A et al 2013 J. Biomed. Mater. Res. 101A 2712

    Article  Google Scholar 

  93. Liu Y, Zhu S, Gu Z, Chen C and Zhao Y 2022 Particuology 69 31–48

    Article  CAS  Google Scholar 

  94. Kladko D V, Falchevskaya A S, Serov N S and Prilepskii A Y 2021 IJMS 22 5266

    Article  Google Scholar 

  95. Kose O, Tomatis M, Leclerc L, Belblidia N B, Hochepied J F, Turci F et al 2020 Chem. Res. Toxicol. 33 2324–2337

    Article  CAS  Google Scholar 

  96. Uboldi C, Urbán P, Gilliland D, Bajak E, Valsami-Jones E, Ponti J et al 2016 Toxicol. in Vitro 31 137–145

    Article  CAS  Google Scholar 

  97. Ma Y, Guo Y, Wu S, Lv Z, Zhang Q and Ke Y 2017 RSC Adv. 7 23560–23572

    Article  CAS  Google Scholar 

  98. Simon M, Saez G, Muggiolu G, Lavenas M, Le Trequesser Q, Michelet C et al 2017 Nanotoxicology 11 134–145

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Financial support from Croatian Science Foundation, Grant HRZZ- IP-2018-01-1493 is greatly acknowledged.

Author information

Authors and Affiliations

  1. Department of Medicinal Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, J.J. Strossmayer University, J. Huttlera 4, 31000, Osijek, Croatia

    Marija Milić

  2. Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia

    Krunoslav Ilić & Ivana Vinković Vrček

  3. Laboratory for Biocolloids and Surface Chemistry, Division of Physical Chemistry, Ruđer Bošković Institute, 10000, Zagreb, Croatia

    Ina Erceg, Darija Domazet Jurašin & Maja Dutour Sikirić

  4. Laboratory for Electron Spin Spectroscopy, Division of Physical Chemistry, Ruđer Bošković Institute, 10000, Zagreb, Croatia

    Nadica Maltar-Strmečki

Authors
  1. Marija Milić
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Krunoslav Ilić
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ina Erceg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Darija Domazet Jurašin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nadica Maltar-Strmečki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ivana Vinković Vrček
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maja Dutour Sikirić
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maja Dutour Sikirić.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 536 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Milić, M., Ilić, K., Erceg, I. et al. Impact of TiO2 nanomaterials with different morphologies and their calcium phosphate composites on hemostasis and immunocompatibility. Bull Mater Sci 46, 187 (2023). https://doi.org/10.1007/s12034-023-03021-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12034-023-03021-2

Keywords

Search

Navigation