The combination of titania nanofilms and silver nanoparticles (NPs) is a very promising material, with antibacterial and osseointegration-induced properties for titanium implant coatings. In this work, we successfully prepared TiO2 nanolayer/Ag NP structures on titanium disks using atomic layer deposition (ALD). The samples were studied by scanning electron microscopy (SEM), X-ray diffraction, X-ray photoelectron spectroscopy (XPS), contact angle measurements, and SEM-EDS. Antibacterial activity was tested against Staphylococcus aureus. The in vitro cytological response of MG-63 osteosarcoma and human fetal mesenchymal stem cells (FetMSCs) was examined using SEM study of their morphology, MTT test of viability and differentiation using alkaline phosphatase and osteopontin with and without medium-induced differentiation in the osteogenic direction. The samples with TiO2 nanolayers, Ag NPs, and a TiO2/Ag combination showed high antibacterial activity, differentiation in the osteogenic direction, and non-cytotoxicity. The medium for differentiation significantly improved osteogenic differentiation, but the ALD coatings also stimulated differentiation in the absence of the medium. The TiO2/Ag samples showed the best antibacterial ability and differentiation in the osteogenic direction, indicating the success of the combining of TiO2 and Ag to produce a multifunctional biocompatible and bactericidal material.

Center of Translational Cancer Research Klinikum Rechts der Isar Technical University Munich Einstein Str 25 81675 Munich Germany

Department of Solid State Engineering Institute of Chemical Technology 16628 Prague Czech Republic

Institute of Cytology of the Russian Academy of Sciences Tikhoretsky Ave 4 194064 Saint Petersburg Russia

Ioffe Institute Polytechnicheskaya 26 194021 Saint Petersburg Russia

Peter the Great Saint Petersburg Polytechnic University Polytechnicheskaya 29 195221 Saint Petersburg Russia

Saint Petersburg Pasteur Institute of Epidemiology and Microbiology 14 Mira Street 197101 Saint Petersburg Russia

Saint Petersburg State University Universitetskaya nab 7 9 199034 Saint Petersburg Russia

Zobrazit více v PubMed

Zhang L.C., Chen L.Y. A Review on Biomedical Titanium Alloys: Recent Progress and Prospect. Adv. Eng. Mater. 2019;21:1801215. doi: 10.1002/adem.201801215. DOI

Kaur M., Singh K. Review on titanium and titanium based alloys as biomaterials for orthopaedic applications. Mater. Sci. Eng. C Mater. Biol. Appl. 2019;102:844–862. doi: 10.1016/j.msec.2019.04.064. PubMed DOI

Valiev R.Z., Prokofiev E.A., Kazarinov N.A., Raab G.I., Minasov T.B., Strasky J. Developing Nanostructured Ti Alloys for Innovative Implantable Medical Devices. Materals. 2020;13:967. doi: 10.3390/ma13040967. PubMed DOI PMC

Stewart C., Akhavan B., Wise S.G., Bilek M.M.M. A review of biomimetic surface functionalization for boneintegrating orthopedic implants: Mechanisms, current approaches, and future directions. Prog. Mater. Sci. 2019;106:100588. doi: 10.1016/j.pmatsci.2019.100588. DOI

Wen C.E., Xu W., Hu W.Y., Hodgson P.D. Hydroxyapatite/titania sol-gel coatings on titanium-zirconium alloy for biomedical applications. Acta Biomater. 2007;3:403–410. doi: 10.1016/j.actbio.2006.10.004. PubMed DOI

Hertz A., Bruce I.J. Inorganic materials for bone repair or replacement applications. Nanomedicine. 2007;2:899–918. doi: 10.2217/17435889.2.6.899. PubMed DOI

He J., Zhou W., Zhou X., Zhong X., Zhang X., Wan P., Zhu B., Chen W. The anatase phase of nanotopography titania plays an important role on osteoblast cell morphology and proliferation. J. Mater. Sci. Mater. Med. 2008;19:3465–3472. doi: 10.1007/s10856-008-3505-3. PubMed DOI

Grigal I.P., Markeev A.M., Gudkova S.A., Chernikova A.G., Mityaev A.S., Alekhin A.P. Correlation between bioactivity and structural properties of titanium dioxide coatings grown by atomic layer deposition. Appl. Surf. Sci. 2012;258:3415–3419. doi: 10.1016/j.apsusc.2011.11.082. DOI

Wu X., Chen S., Ji W., Shi B. The risk factors of early implant failure: A retrospective study of 6113 implants. Clin. Implant Dent. Relat. Res. 2021;23:280–288. doi: 10.1111/cid.12992. PubMed DOI

Hamilton H., Jamieson J. Deep infection in total hip arthroplasty. Can. J. Surg. 2008;51:111–117. PubMed PMC

Mikhailova E.O. Silver Nanoparticles: Mechanism of Action and Probable Bio-Application. J. Funct. Biomater. 2020;11:84. doi: 10.3390/jfb11040084. PubMed DOI PMC

Qin Z., Zheng Y., Wang Y., Du T., Li C., Wang X., Jiang H. Versatile roles of silver in Ag-based nanoalloys for antibacterial applications. Coord. Chem. Rev. 2021;449:214218. doi: 10.1016/j.ccr.2021.214218. DOI

Spriano S., Yamaguchi S., Baino F., Ferraris S. A critical review of multifunctional titanium surfaces: New frontiers for improving osseointegration and host response, avoiding bacteria contamination. Acta Biomater. 2018;79:1–22. doi: 10.1016/j.actbio.2018.08.013. PubMed DOI

Miikkulainen V., Leskelä M., Ritala M., Puurunen R.L. Crystallinity of inorganic films grown by atomic layer deposition: Overview and general trends. J. Appl. Phys. 2013;113:021301. doi: 10.1063/1.4757907. DOI

Gupta B., Hossain M.A., Riaz A., Sharma A., Zhang D., Tan H.H., Jagadish C., Catchpole K., Hoex B., Karuturi S. Recent Advances in Materials Design Using Atomic Layer Deposition for Energy Applications. Adv. Funct. Mater. 2021;32:2109105. doi: 10.1002/adfm.202109105. DOI

Kariniemi M., Niinisto J., Hatanpaa T., Kemell M., Sajavaara T., Ritala M., Leskela M. Plasma-Enhanced Atomic Layer Deposition of Silver Thin Films. Chem. Mater. 2011;23:2901–2907. doi: 10.1021/cm200402j. DOI

Wack S., Lunca Popa P., Adjeroud N., Guillot J., Pistillo B.R., Leturcq R. Large-Scale Deposition and Growth Mechanism of Silver Nanoparticles by Plasma-Enhanced Atomic Layer Deposition. J. Phys. Chem. C. 2019;123:27196–27206. doi: 10.1021/acs.jpcc.9b06473. DOI

Nazarov D.V., Zemtsova E.G., Solokhin A.Y., Valiev R.Z., Smirnov V.M. Modification of the Surface Topography and Composition of Ultrafine and Coarse Grained Titanium by Chemical Etching. Nanomaterials. 2017;7:15. doi: 10.3390/nano7010015. PubMed DOI PMC

Nazarov D.V., Smirnov V.M., Zemtsova E.G., Yudintceva N.M., Shevtsov M.A., Valiev R.Z. Enhanced Osseointegrative Properties of Ultra-Fine-Grained Titanium Implants Modified by Chemical Etching and Atomic Layer Deposition. ACS Biomater. Sci. Eng. 2018;4:3268–3281. doi: 10.1021/acsbiomaterials.8b00342. PubMed DOI

Nazarov D., Zemtsova E., Smirnov V., Mitrofanov I., Maximov M., Yudintceva N., Shevtsov M. The Effects of Chemical Etching and Ultra-Fine Grain Structure of Titanium on MG-63 Cells Response. Metals. 2021;11:510. doi: 10.3390/met11030510. DOI

Nazarov D., Rudakova A., Borisov E., Popovich A. Surface Modification of Additively Manufactured Nitinol by Wet Chemical Etching. Materials. 2021;14:7683. doi: 10.3390/ma14247683. PubMed DOI PMC

Owens D.K., Wendt R.C. Estimation of the surface free energy of polymers. J. Appl. Polym. Sci. 1969;13:1741–1747. doi: 10.1002/app.1969.070130815. DOI

Chatakun P., Nunez-Toldra R., Diaz Lopez E.J., Gil-Recio C., Martinez-Sarra E., Hernandez-Alfaro F., Ferres-Padro E., Giner-Tarrida L., Atari M. The effect of five proteins on stem cells used for osteoblast differentiation and proliferation: A current review of the literature. Cell. Mol. Life Sci. 2014;71:113–142. doi: 10.1007/s00018-013-1326-0. PubMed DOI PMC

Minjauw M.M., Solano E., Sree S.P., Asapu R., Van Daele M., Ramachandran R.K., Heremans G., Verbruggen S.W., Lenaerts S., Martens J.A., et al. Plasma-Enhanced Atomic Layer Deposition of Silver Using Ag(fod)(PEt3) and NH3-Plasma. Chem. Mater. 2017;29:7114–7121. doi: 10.1021/acs.chemmater.7b00690. DOI

Amusan A.A., Kalkofen B., Gargouri H., Wandel K., Pinnow C., Lisker M., Burte E.P. Ag films grown by remote plasma enhanced atomic layer deposition on different substrates. J. Vac. Sci. Technol. A. 2016;34:01A126. doi: 10.1116/1.4936221. DOI

Niemelä J.-P., Marin G., Karppinen M. Titanium dioxide thin films by atomic layer deposition: A review. Semicond. Sci. Technol. 2017;32:093005. doi: 10.1088/1361-6641/aa78ce. DOI

Nazarov D., Ezhov I., Yudintceva N., Mitrofanov I., Shevtsov M., Rudakova A., Maximov M. MG-63 and FetMSC Cell Response on Atomic Layer Deposited TiO2 Nanolayers Prepared Using Titanium Tetrachloride and Tetraisopropoxide. Coatings. 2022;12:668. doi: 10.3390/coatings12050668. DOI

Bhat B., Viswanathan P., Chandanala S., Prasanna S.J., Seetharam R.N. Expansion and characterization of bone marrow derived human mesenchymal stromal cells in serum-free conditions. Sci. Rep. 2021;11:3403. doi: 10.1038/s41598-021-83088-1. PubMed DOI PMC

Yudintceva N.M., Bogolyubova I.O., Muraviov A.N., Sheykhov M.G., Vinogradova T.I., Sokolovich E.G., Samusenko I.A., Shevtsov M.A. Application of the allogenic mesenchymal stem cells in the therapy of the bladder tuberculosis. J. Tissue Eng. Regen. Med. 2018;12:e1580–e1593. doi: 10.1002/term.2583. PubMed DOI

Motola M., Capek J., Zazpe R., Bacova J., Hromadko L., Bruckova L., Ng S., Handl J., Spotz Z., Knotek P., et al. Thin TiO2 Coatings by ALD Enhance the Cell Growth on TiO2 Nanotubular and Flat Substrates. ACS Appl. Bio Mater. 2020;3:6447–6456. doi: 10.1021/acsabm.0c00871. PubMed DOI

Chuang Y.-C., Wang L., Feng K.-C., Subramanian A., Chang C.-C., Simon M., Nam C.-Y., Rafailovich M. The Role of Titania Surface Coating by Atomic Layer Deposition in Improving Osteogenic Differentiation and Hard Tissue Formation of Dental Pulp Stem Cells. Adv. Eng. Mater. 2021;23:2100097. doi: 10.1002/adem.202100097. DOI

Benhabbour S.R., Sheardown H., Adronov A. Cell adhesion and proliferation on hydrophilic dendritically modified surfaces. Biomaterials. 2008;29:4177–4186. doi: 10.1016/j.biomaterials.2008.07.016. PubMed DOI

Majhy B., Priyadarshini P., Sen A.K. Effect of surface energy and roughness on cell adhesion and growth—Facile surface modification for enhanced cell culture. RSC Adv. 2021;11:15467–15476. doi: 10.1039/D1RA02402G. PubMed DOI PMC

Radtke A., Jedrzejewski T., Kozak W., Sadowska B., Wieckowska-Szakiel M., Talik E., Mäkelä M., Leskelä M., Piszczek P. Optimization of the Silver Nanoparticles PEALD Process on the Surface of 1-D Titania Coatings. Nanmaterials. 2017;7:193. doi: 10.3390/nano7070193. PubMed DOI PMC

Ferraris S., Spriano S. Antibacterial titanium surfaces for medical implants. Mater. Sci. Eng. C Mater. Biol. Appl. 2016;61:965–978. doi: 10.1016/j.msec.2015.12.062. PubMed DOI

Selvamani V., Kadian S., Detwiler D.A., Zareei A., Woodhouse I., Qi Z., Peana S., Alcaraz A.M., Wang H., Rahimi R. Laser-Assisted Nanotexturing and Silver Immobilization on Titanium Implant Surfaces to Enhance Bone Cell Mineralization and Antimicrobial Properties. Langmuir. 2022;38:4014–4027. doi: 10.1021/acs.langmuir.2c00008. PubMed DOI

Mattila P.K., Lappalainen P. Filopodia: Molecular architecture and cellular functions. Nat. Rev. Mol. Cell Biol. 2008;9:446–454. doi: 10.1038/nrm2406. PubMed DOI

Sengstock C., Diendorf J., Epple M., Schildhauer T.A., Koller M. Effect of silver nanoparticles on human mesenchymal stem cell differentiation. Beilstein J. Nanotechnol. 2014;5:2058–2069. doi: 10.3762/bjnano.5.214. PubMed DOI PMC

Zhang Y.Y., Zhu Y., Lu D.Z., Dong W., Bi W.J., Feng X.J., Wen L.M., Sun H., Qi M.C. Evaluation of osteogenic and antibacterial properties of strontium/silver-containing porous TiO2 coatings prepared by micro-arc oxidation. J. Biomed. Mater. Res. Part B Appl. Biomater. 2021;109:505–516. doi: 10.1002/jbm.b.34719. PubMed DOI

Samberg M.E., Loboa E.G., Oldenburg S.J., Monteiro-Riviere N.A. Silver nanoparticles do not influence stem cell differentiation but cause minimal toxicity. Nanomedicine. 2012;7:1197–1209. doi: 10.2217/nnm.12.18. PubMed DOI PMC

Rajendran A., Kapoor U., Jothinarayanan N., Lenka N., Pattanayak D.K. Effect of Silver-Containing Titania Layers for Bioactivity, Antibacterial Activity, and Osteogenic Differentiation of Human Mesenchymal Stem Cells on Ti Metal. ACS Appl. Bio Mater. 2019;2:3808–3819. doi: 10.1021/acsabm.9b00420. PubMed DOI

Xu N., Fu J., Zhao L., Chu P.K., Huo K. Biofunctional Elements Incorporated Nano/Microstructured Coatings on Titanium Implants with Enhanced Osteogenic and Antibacterial Performance. Adv. Healthc. Mater. 2020;9:e2000681. doi: 10.1002/adhm.202000681. PubMed DOI

Yang F., Chang R., Webster T.J. Atomic Layer Deposition Coating of TiO2 Nano-Thin Films on Magnesium-Zinc Alloys to Enhance Cytocompatibility for Bioresorbable Vascular Stents. Int. J. Nanomed. 2019;14:9955–9970. doi: 10.2147/IJN.S199093. PubMed DOI PMC

Ren B., Wan Y., Liu C., Wang H., Yu M., Zhang X., Huang Y. Improved osseointegration of 3D printed Ti-6Al-4V implant with a hierarchical micro/nano surface topography: An in vitro and in vivo study. Mater. Sci. Eng. C Mater. Biol. Appl. 2021;118:111505. doi: 10.1016/j.msec.2020.111505. PubMed DOI

Ylivaara O.M.E., Langner A., Liu X., Schneider D., Julin J., Arstila K., Sintonen S., Ali S., Lipsanen H., Sajavaara T., et al. Mechanical and optical properties of as-grown and thermally annealed titanium dioxide from titanium tetrachloride and water by atomic layer deposition. Thin Solid Film. 2021;732:138758. doi: 10.1016/j.tsf.2021.138758. DOI

Kilpi L., Ylivaara O.M.E., Vaajoki A., Malm J., Sintonen S., Tuominen M., Puurunen R.L., Ronkainen H. Microscratch testing method for systematic evaluation of the adhesion of atomic layer deposited thin films on silicon. J. Vac. Sci. Technol. A Vac. Surf. Film. 2016;34:01A124. doi: 10.1116/1.4935959. DOI

Solovyev A.A., Markeev A.M., Tetyukhin D.V., Kozlov E.N., Molchanov S.A. Applications of atomic layer deposition in implant dentistry. Eur. Cells Mater. 2014;27:17.

Picosun Strengthens Its Presence in the Healthcare Industries. [(accessed on 3 May 2022)]. Available online: https://markets.businessinsider.com/news/stocks/picosun-strengthens-its-presence-in-the-healthcare-industries-1028237785.

Enhancement of biocompatibility of anodic nanotube structures on biomedical Ti-6Al-4V alloy via ultrathin TiO2 coatings

Ultrathin TiO2 Coatings via Atomic Layer Deposition Strongly Improve Cellular Interactions on Planar and Nanotubular Biomedical Ti Substrates