Synergy of antimicrobial agents incorporated in durable bio-glass coatings for endosseous implants (SYNERGLASS)


Project Director: Dr. George STAN

Project ID:  PN-III-P1-1.1-TE-2016-1501

Project Director:  Dr. George Stan

Project Type: National

Project Program: HUMAN RESOURCES, Young Teams

Funded by:  Romanian National Authority for Scientific Research, UEFISCDI

Contractor: National Institute of Materials Physics

Project Status: Finished

Start Date: 2 May, 2018

End Date: 15 October, 2020

 

Project summary: 

Nowadays, antibiotic resistance becomes an important issue; as bacterial strains resistant to all known antibiotics appear, we are entering the “post-antibiotic era”. Acute complications emerge after implant surgery, as trauma will weaken the local immune response and allow pathogens to adhere and rapidly evolve within the implantation site. Severity increases in dentistry, where one cannot achieve an oral aseptic environment during implantation. Hence, the project targets to unveil routes towards the synergic coupled effect of antimicrobial oxide agents (i.e. Ga2O3, CuO, Fe3O4, Ag2O), with different action mechanisms, incorporated in bio-glass magnetron sputtered layers, and thereby, the development of an advanced generation of implant coatings, capable to meet the current challenging requirements of osseous implantology: mechanical durability, match of coating and metallic substrate coefficients of thermal expansion, conservation of network connectivity along with bioactivity and osseointegration ability, match of bone healing rate with coating degradation speed, and effective antimicrobial action against a wide spectrum of pathogens. This will ineluctably translate in the safe and long-lasting performance of functionalized medical devices. Solutions to i) boost and control the duration of antimicrobial effect by means of sacrificial layers, ii) eliminate costly and time consuming stages from the intricate technological chain, and iii) improve the existing in vitro testing protocols, will be also proposed. The degree of innovation comprised in project goals can enable surpassing the current knowledge boundaries in the field of implant coatings, and thus, generate premises for technological transfer to industry and local economic growth. Besides the scientific targets, the project will aim to attract valuable human resources in national research and create opportunities of continual professional formation for young researchers to expand their knowledge and skills.

 

Project Objectives: 

GENERAL OBJECTIVE:   Unveiling Routes Towards the Synergic Effect of Antimicrobial Agents Incorporated in Durable Bioactive Glass Sputtered Coatings

SPECIFIC OBJECTIVES:

O1: Synthesis by MQ of novel compositional series of SBG and PBG powders with designed single, double, or triple antimicrobial oxide substitutions into the base formulation. Functional optimization. – Realized [RST 1/2018 & RST 2/2019].

O2: Fabrication by RF-MS, from optimized novel MQ BG materials, of single (SBG/Ti) and doubled layered (PBG/SBG/Ti) coatings with different thicknesses and compositions/structures. – Realized [RST 2/2019 & RST 3/2020].

O3: Exploratory alternative fabrication of SBG coatings by RF-MS directly from raw oxide precursors. – Realized [RST 2/2019].

O4: Cross-examination of the physical-chemical and functional (adherence, hardness, elastic modulus, wear resistance, surface energy, degradability, ion release, bioactivity, antimicrobial efficiency, cytocompatibility) of the BG powders and coatings by multiparametric analyses. Optimization. – Realized [RST 2/2019 & RST 3/2020].

O5: Application of the optimized BG coatings designs to the functionalization of implants with complex geometry (e.g. dental screws) by using a planetary rotation holder developed in project TE73/2015. “Cold-implantation” experiments. – Realized [RST 3/2020].

O6:  Consolidation of the research team by the addition of young researchers with complementary skills and active interests in biomedical field. Dissemination of the relevant scientific results of project. – Realized [RST 1/2018, RST 2/2019 & RST 3/2020].

Stage I summary:

Stage I of the research project (2018.05.02 - 2018.12.05) was dedicated to both the preparation by melt-quenching and characterization of the innovative bioactive silicate- and phosphate-based glass systems substituted with CuO and/or Ga2O3, as well as to the first experiments of thin films fabrication by the radio-frequency magnetron sputtering (RF-MS) technique.

Delivered results:

  • A scientific study on the manufacture and characterization of series of the new compositional systems of silica-based (SBG – SiO2-CaO-P2O5-MgO) and phosphate-based (PBG – P2O5-CaO-Na2O-Fe2O5) bioactive glasses simple, and substituted with CuO and/or Ga2O3 (2 – 5 mol%);
  • A scientific study on the first (preliminary) preparations and characterizations of films synthesized by RF-MS technique from the newly synthesized SBG and PBG systems;
  • 1 participation to international conferences.

The scientific report cannot be yet divulged on the project website, as the results are in the process of being published, but it can be accessed upon request at UEFISCDI.

2018: THE SYNTHETIC SCIENTIFIC REPORT no. 1 in .pdf format is available at UEFISCDI, and can be accessed by request.

 

Stage II summary:

Stage II of the research project (2018.12.06 - 2019.12.05) was dedicated to the (i) selection of the most promising bioactive glass formulation from the point of view of coupled cytocompatibility / antimicrobial activity; (ii) study of (magnetron sputtering) deposition conditions influence on the composition, structure and functional performance of implant coatings based on silicate (SBG) and / or phosphate (PBG) bioactive coatings with antimicrobial effect; (iii) testing a new concept for synthesizing SBG films; and (iv) dissemination of results by specific means [i.e., scientific articles published in Web of Science® indexed journals situated in the first two quartiles (Q1 and Q2) of the Materials Science and Engineering domains; presentations at scientific events with international participation; project web page)].

Delivered results:

  • A scientific study on the selection of the most promising bioactive glass compositions with antimicrobial effect and unaltered cytocompatibility;
  • A scientific study regarding the influence of the deposition conditions on the composition, structure and functional performance of the implant-type coatings based on silicate (SBG) and phosphate (PBG) bioactive glasses with antimicrobial effect;
  • An innovative synthesis method of SBG films;
  • 3 articles published in Web of Science® indexed journals;
  • 3 participations to international conferences.

The scientific report cannot be yet divulged on the project website, as the results are in the process of being published, but it can be accessed upon request at UEFISCDI.

2019: THE SYNTHETIC SCIENTIFIC REPORT no. 2 in .pdf format is available at UEFISCDI, and can be accessed by request.

 

Stage III summary:

Stage III of the research project (2019.12.06 – 2020.10.15) was dedicated to the (i) final evaluations and verifications of the physico-chemical and in vitro biological performance of the mono- and bi-layered implant-type coatings based on bioactive silicate (SBG) and/or phosphate (PBG) glasses with antimicrobial activity; (ii) application of the refined/optimized BG deposition recipes for the functionalization of real implants with complex geometry (i.e., dental screws), followed by "cold implantation" experiments in a sheep jaw bone and evaluation of morphological changes induced by the dynamic mechanical stresses inherent to the process of insertion and screw removal from bone of the dental implant fixtures; and (iii) dissemination of project results by specific means [i.e., submission of 4 manuscripts to Web of Science® indexed journals situated in the first two quartiles (Q1 and Q2) of the Materials Science and Engineering domains; 2 presentations at scientific events with international participation; drafting 1 patent request; and on the project web page)].

Delivered results:

  • A scientific study concerning the application of the refined/optimized BG deposition recipes for the functionalization of real implants with complex geometry (i.e., dental screws) and their mechanical performance based on “cold implantation” experiments;
  • Demonstrators of dental implants bio-functionalized with (i) mono-layered coatings produced by the innovative synthesis method proposed in the project, and (ii) bi-layered coatings, fabricated by the classical RF-MS technological algorithm, and composed of a layer with excellent biomineralization capacity in contact with metal implant and a superficial resorbable sacrificial layer with antimicrobial effect;
  • 4 manuscripts submitted to Web of Science® indexed journals situated in the first two quartiles (Q1 and Q2) of Materials Science domains;
  • 2 participations to international conferences;
  • 1 patent request submitted to State Office for Inventions and Trademarks (OSIM).

The scientific report cannot be yet divulged on the project website, as the results are in the process of being published, but it can be accessed upon request at UEFISCDI.

2020: THE SYNTHETIC SCIENTIFIC REPORT no. 3 (final) in .pdf format is available at UEFISCDI, and can be accessed by request.

The scientific objectives of the project have been achieved. The project results encourage us to continue the researches and focus in the near future not only on increasing the international visibility of project results, and communicating the recorded progresses at scientific events, but also in Technology and Innovation fairs/expos, in order to identify industrial partners interested to transfer the optimized recipes for functionalization of implants with antimicrobial sacrificial layers by RF-MS.

The project goals concerning the dissemination of novel results were achieved as well, both by the participation to international scientific conferences (1 invited lecture, 1 oral presentation and 4 poster presentations) and by publication of 3 articles in Web of Science® journals situated in the Q1 and Q2 quartiles, and submission for evaluation of another 4 more papers to Web of Science® journals situated in the Q1 and Q2 quartiles. The dissemination tasks will continue also after the end of the project. Based on the latest results obtained in the project, the research team has under preparation 3 more scientific papers that will soon be sent for evaluation to journals situated in the Q1 quartile of "Science Citation Index Expanded" subdomains: Materials Science – Biomaterials, Materials Science – Coatings & Films or Materials Science – Ceramics.

  • 2020: Any-Cristina SERGENTU, 3rd year of study (final), Faculty of Medical Engineering, University POLITEHNICA of Bucharest, effectuated (01.02.2020 - 01.06.2020) the research studies in the framework of her License Thesis entitled: “COATINGS BASED ON NEW COMPOSITIONAL SYSTEMS OF BIOACTIVE SILICATE GLASSES WITHOUT ALKALINE OXIDES PREPARED BY RADIO-FREQUENCY MAGNETRON SPUTTERING”, under the scientific supervision of  Dr. George Stan (INCDFM, TE04/2018 project director), As.Dr. Andrea Cucuruz (UPB-FIM) si Prof.Dr. Cristina Ghitulica (UPB-FIM).

Web of Science® articles - published or accepted:

  • 01. A.C. Popa^, H.R. Fernandes, M. Necsulescu, C. Luculescu, M. Cioangher, V. Dumitru, B.W. Stuart, D.M. Grant, G.E. Stan^,*, J.M.F. Ferreira*, Antibacterial efficiency of alkali-free bioglasses incorporating ZnO and/or SrO as therapeutic agents; CERAM INT 45 (2019) 4368–4380. https://doi.org/10.1016/j.ceramint.2018.11.112.
  • 02. S.L. Iconaru, A. Groza, G.E. Stan^, D. Predoi, S. Gaiaschi, R. Trusca, C.M. Chifiriuc, L. Marutescu, T. Tite, G.A. Stanciu, R. Hristu, L. Ghegoiu, M.L. Badea, C.S. Turculet, M. Ganciu, P. Chapon, Preparations of silver/montmorillonite biocomposite multilayers and their antifungal activity, COATINGS 9 (2019) 817. https://doi.org/10.3390/coatings9120817.
  • 03. H.R. Fernandes, A. Gaddam, A. Rebelo, D. Brazete, G.E. Stan^, J.M.F. Ferreira, Bioactive glasses and glass-ceramics for healthcare applications in bone regeneration and tissue engineering, MATERIALS 11 (2018) 2530. https://doi.org/10.3390/ma11122530.
  • 04. G.E. Stan^,*, T. Tite, A.C. Popa^, I.M. Chirica^, C.C. Negrila^, C. Besleaga^, I. Zgura, A.C. Sergentu, G. Popescu-Pelin, D. Cristea, L.E. Ionescu, M. Necsulescu, H.R. Fernandes, J.M.F. Ferreira, The beneficial mechanical and biological outcomes of thin copper-gallium doped silica-rich bio-active glass implant-type coatings; COATINGS 10 (2020) 1119. https://doi.org/10.3390/coatings10111119.
  • 05. G. Popescu-Pelin, C. Ristoscu, L. Duta, I. Pasuk^, G.E. Stan^, M.S. Stan, M. Popa, M.C. Chifiriuc, C. Hapenciuc, F.N. Oktar, A. Nicarel, I.N. Mihailescu*, Fish bone derived bi-phasic calcium phosphate coatings fabricated by pulsed laser deposition for biomedical applications; MAR DRUGS 18 (2020) 623. https://doi.org/10.3390/md18120623.
  • 06. T. Tite, A.C. Popa^, I.M. Chirica^, B.W. Stuart, A.C. Galca^, L.M. Balescu^, G. Popescu-Pelin, D.M. Grant, J.M.F. Ferreira, G.E. Stan^,*, Phosphate bioglass thin-films: Cross-area uniformity, structure and biological performance tailored by the simple modification of magnetron sputtering gas pressure; APPL SURF SCI 541 (2021) 148640. https://doi.org/10.1016/j.apsusc.2020.148640.
  • 07. A. Gaddam*, A.R. Allu, H.R. Fernandes, G.E. Stan^, C.C. Negrila^, A.P. Jamale, F. Mear, L. Montagne, J.M.F. Ferreira*, Role of vanadium oxide on the lithium silicate glass structure and properties; J AM CERAM SOC 104 (2021) 2495. https://doi.org/10.1111/jace.17671.
  • 08. B.W. Stuart*, G.E. Stan^, A.C. Popa^, M.J. Carrington, I. Zgura, M. Necsulescu, D.M. Grant*, New solutions for combatting implant bacterial infection based on silver nano-dispersed and gallium incorporated phosphate bioactive glass sputtered films: A preliminary study; BIOACTIVE MATER 8 (2022) 325. https://doi.org/10.1016/j.bioactmat.2021.05.055.
  • 09. T. Tite, A.C. Popa^, B.W. Stuart, H.R. Fernandes, I.M. Chirica^, G.A. Lungu, D. Macovei, C. Bartha, L. Albulescu, C. Tanase, S. Nita, N. Rusu, D.M. Grant, J.M.F. Ferreira, G.E. Stan*,^, Independent and complementary bio-functional effects of CuO and Ga2O3 incorporated as therapeutic agents in silica- and phosphate-based bioactive glasses; J MATERIOMICS 8 (2022) 893. https://doi.org/10.1016/j.jmat.2021.12.009.

OSIM Patent request:

  • 01. G. Stan^, A.C. Popa^, C. Besleaga^, Procedure for obtaining endoosseous implants coated with continuous, porous, resorbable and antimicrobial bio-active phosphatic glass layers; OSIM patent RO134819 / published in BOPI no. 3/2021.

International Conferences:

  • 01. G.E. Stan^,*, A.C. Popa^, C. Besleaga^, J.M.F. Ferreira, Comparative in vitro behaviour of bioglass coatings in simulated body media with improved biomimicry: Challenging a paradigm, 5th edition of International Conference on Analytical and Nanoanalytical Methods for Biomedical and Environmental Sciences (IC-ANMBES), 23–25 May 2018, Brasov, Romania (invited);
  • 02. A.C. Popa^, T. Tite, I.M. Bogdan^,*, H.R. Fernandes, M. Necsulescu, C. Luculescu, M. Cioangher, V. Dumitru, B.W. Stuart, D.M. Grant, J.M.F. Ferreira, G.E. Stan^, Synergetic antibacterial effect in alkali-free bio-glasses incorporated with ZnO and/or SrO as therapeutic agents, EMRS Conference – Spring Meeting, 27–31 May 2019, Nice, France (poster);
  • 03. T. Tite, A.C. Popa^, A.C. Galca^, L.M. Balescu^, I.M. Bogdan^,*, B.W. Stuart, G. Pelin-Popescu, G.E. Stan^, Tuning the structure and biological response of sputtered phosphate bioglass films by the deposition pressure, EMRS Conference – Spring Meeting, 27–31 May 2019, Nice, France (poster);
  • 04. G.E. Stan^,*, A.C. Popa^, V.M.F. Marques, A.C. Galca^, C. Ghica, M.A. Husanu, M. Enculescu, C. Tanase, D.U. Tulyaganov, J.M.F. Ferreira, Functional performance of bioactive silica-based glass implant coatings deposited by magnetron sputtering onto dental screws, EuroNanoForum, 12–14 June 2019, Bucharest, Romania (poster);
  • 05. I.M. Chirica^,*,  T. Tite,  A.C. Popa^, A.C. Galca^, L.M. Balescu^, G. Popescu-Pelin, B.W. Stuart, D.M. Grant, G.E. Stan^, Physico-chemical and biological characterization of phosphate bio-glass implant-type coatings fabricated by radio-frequency magnetron sputtering, 44th edition of the International Conference and Expo on Advanced Ceramics and Composites (ICACC 2020), 26–31 January 2020, Daytona Beach, SUA (poster).
  • 06. G.E. Stan^,*, A.C. Popa^, C. Tanase, H.R. Fernandes, J.M.F. Ferreira, Magnetron sputtered bioactive glass implant-type coatings: the road so far and the road ahead, 5th edition of International Workshop on Materials Physics (IWMP), 21 September 2020, Magurele, Romania (oral).

 

*corresponding/presenting author

^project team member

GEORGE E. STAN, PhD in Materials Engineering
Senior Researcher I
Telephone: +40-(0)21-2418 128 or +40-(0)21-2418 153
Department: Laboratory of Multifunctional Materials and Structures

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