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: In progress

Start Date: 2 March, 2018

End Date: 30 April, 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 economical 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:

O1Synthesis by MQ of novel compositional series of SBG and PBG powders with designed single, double, or triple antimicrobial oxidic substitutions into the base formulation. Functional optimization. -- Realized.

O2Fabrication 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.

O3Exploratory alternative fabrication of SBG coatings by RF-MS directly from raw oxide precursors.

O4Cross-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.

O5Application 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.

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.

Stage I summary:

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

Delivered results:

  • Manufacture and characterization of new compositional systems of silica-based (SBG) and phosphate-based (PBG) bioactive glasses simple, and substituted with substituted with CuO and/or Ga2O3;
  • The first preparations and characterizations of films synthesized by RF-MS technique from the new SBG and PBG systems synthesized in the form of powders;
  • A participation to international conferences.

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 domaines; 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 implantological coatings based on silicate (SBG) and phosphate (PBG) bioactive glasses with antimicrobial effect;
  • An innovative synthesis method of SBG films;
  • Two articles published in Web of Science® indexed journals;
  • Three participations to international conferences.

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

  • 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 engineeringMATERIALS 11 (2018) 2530. https://doi.org/10.3390/ma11122530.

Manuscripts submitted for evaluation to Web of Science® journals:

  • 04. 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 convenient modification of magnetron sputtering gas pressure; submitted to APPL SURF SCI (2020).

Manuscripts in preparation:

  • 05. B.W. Stuart, G.E. Stan^, A.C. Popa^, M.J. Carrington, I. Zgura, M. Necsulescu, D.M. Grant, Tentative title: New solutions capable to combat implant bacterial infection based on phosphate bioactive glass sputtered films: A preliminary study; in preparation (manuscript to be submitted in August - September 2020).
  • 06. G.E. Stan^,*, A.C. Popa^, C. Besleaga^, C.C. Negrila^, J.M.F. Ferreira, Tentative title: Bioglass synthesis by physical vapour condensation; in preparation (manuscript to be submitted in August - September 2020).
  • 07. A.C. Popa^, H.R. Fernandes, M. Enculescu, C. Besleaga^, C. Negrila^, I. Zgura, B.W. Stuart, D.M. Grant, J.M.F. Ferreira, G.E. Stan^,*, Tentative title: Functional silica-based bioactive glass implant-type coatings fabricated by magnetron sputtering: Answers to the unresolved questions; in preparation (manuscript to be submitted in September - October 2020).
  • 08. T. Tite, H.R. Fernandes, B.W. Stuart, A.C. Popa^, C.R. Luculescu^, G.A. Lungu, D. Macovei, M.A. Husanu,  L. Albulescu, C. Tanase, S. Nita, N. Rusu, D.M. Grant, J.M.F. Ferreira, G.E. Stan^,*, Tentative title: Individual and coupled bio-functional effects of CuO and Ga2O3 substitution of in silicate- and phosphate-based bioactive glasses; in preparation.
  • 09. T. Tite, H.R. Fernandes, A.C. Popa^, I.M. Chirica, D. Cristea, J.M.F. Ferreira, G.E. Stan^,*, Tentative title: Copper and Gallium substituted silicate bio-glasses films synthesized by magnetron sputtering as promising mechanically-enhanced cytocompatible biofunctional solutions; in preparation.

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 International Conference and Expo on Advanced Ceramics and Composites (ICACC 2020), 26–31 January 2020, Daytona Beach, SUA (poster).

 

*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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