NIMP| Enhancement of dental implants biointegration by coating with bioglass thin films with osteoinductive and antimicrobial properties (AUGLASS)

Enhancement of dental implants biointegration by coating with bioglass thin films with osteoinductive and antimicrobial properties (AUGLASS)

Project Director: Dr. George STAN

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Project ID: PN-II-RU-TE-2014-4-0180

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: 1 October, 2015

End Date: 30 November, 2017

Project summary:

The project aims to develop and test in vivo a new generation of dental implants functionalized with bioglass (BG) coatings with osteoinductive and antimicrobial properties, capable to enable a faster osseointegration, safety and comfort, a high success rate, and long lifetime. The project will build on a rich experience in fabricating BG coatings by magnetron sputtering (RF-MS) and a trans-disciplinary and dynamic team, constituted of young researchers with complementary expertise. The BG implant-coating design refinements and in vitro functional interrogations will continue, in order to maximize the biological response, allowing, in a next stage, the in vivo testing on animal model of the true potential of BG films synthesized by RF-MS to induce a rapid and long-lasting osseointegration. The novel research directions to be addressed – determination of BG critical coating thickness, attainment of BG layer dissolution/tissue reconstruction equilibrium, tailoring of the surface energy targeting the augmentation of osseointegration, study of the synergy of various antimicrobial agents, or the preliminary studies regarding alkali-free BG films from innovative formulations – will work fluidly for the accomplishment of the project objectives. Another project priority is the creation of a critical mass of young researchers able to coherently implement complex themes, and to actively involve in national/international consortia for the development of the biomedical domain.

Project objectives:

GENERAL OBJECTIVE: Optimization of the biological response of dental implants functionalized with bioglass thin films and the demonstration of their superior performance to conventional implants by in vitro and in vivo studies.

1^st STAGE (01-X-2015 - 04-XII-2015)

Synthesis of alkali-free bioactive glass (BG) powders and thin films with antimicrobial activity and coefficients of thermal expansion compatible with the titanium implant substrates. ACHIEVED [Report 1/2015].
Preliminary experiments of thin films fabrication using the new BG compositional systems as magnetron cathode targets. ACHIEVED [Report 1/2015].

2^nd STAGE (04-XII-2015 - 04-XII-2016)

Finalization of the synthesis of alkali-free BG powders to be used for manufacturing the magnetron cathode targets. ACHIEVED [Report 2/2016].
Preparation and testing of the BG implant coatings. ACHIEVED [Report 2/2016].
Exhaustive morphological, structural, compositional, surface energy, electrical, and mechanical characterization. ACHIEVED [Report 2/2016].
Studies exploring the possibilities to scale-up to micro-production level the BG coating fabrication protocols I. ACHIEVED [Report 2/2016].
Testing in vitro the biodisponibility of the BG coatings developed in the project framework. ACHIEVED [Report 2/2016].
Management and dissemination I. ACHIEVED [Report 2/2016].

3^rd STAGE (04-XII-2016 - 30-XI-2017)

Studies exploring the possibilities to scale-up to micro-production level the BG coating fabrication protocols II. ACHIEVED [Report 3/2017].
Methods for modulating the degradation/dissolution rate of BG implant-type coatings to match it to the rate of bone regeneration. ACHIEVED [Report 3/2017].
Fabrication of test batches of optimized BG coatings onto real dental fixtures. ACHIEVED [Report 3/2017].
Finalization of the BG coatings in vitro evaluation. ACHIEVED [Report 3/2017].
In vivo testing of the osseointegration and biocompatibility of dental implants biofunctionalized with the optimized BG coatings. ACHIEVED [Report 3/2017].
Management and dissemination II. ACHIEVED [Report 3/2017].

RESEARCH TEAM STRUCTURE

George Stan (GS), Project Proposal Leader, PhD in Materials Engineering since 2011: will coordinate all the project activities, research team, resources and project budget decisions. GS will coordinate directly the research activities corresponding to WP1, WP2, WP3 (regarding the Fabrication and Physico-chemical Characterization of Materials) and WP6 (regarding the Management and Dissemination tasks) work packages.

Adrian Popa (AP), Doctor of Medicine, PhD in Medical Sciences since 2015: is a highly trained specialist in in vitro and in vivo assays, having extensive expertise in specific biology analysis techniques (cell culture, SELDI, ELISA, Immunofluorescence techniques, PCR), data processing and interpretation, as well as in scanning/transmission electron microscopy. AP will be in the framework of the project the leader of the WP4 and WP5 (regarding the In Vitro and In Vivo Assay of Implant-type Coatings) work packages. AP will be also involved in the WP6 (Dissemination) work package, as well as in the WP2 and WP3 (regarding the Fabrication and Physico-chemical Characterization of Implant-type Coatings) work packages.

Cristina Besleaga (CB), Physicist, PhD in Physics since 2013: is a young researcher with excellent skills in glass and ceramic powder synthesis and thin films fabrication by magnetron sputtering and pulsed laser deposition. She has also a good experience in structural (XRD, XRR, FTIR), morpho-compositional (SEM, AFM, EDS) and electrical characterization of materials (both in bulk and thin film form). CB will take part actively in WP1, WP2, WP3 (regarding the Fabrication and Physico-chemical Characterization of Materials) and WP6 (Dissemination) work packages.

Marius Husanu (MH), Physicist, PhD in Physics since 2011: has a wide expertise in the investigation of physical properties of two- (surfaces, interfaces) and one-dimensional systems using photoelectron spectroscopy (XPS), scanning tunneling microscopy (STM), photoemission microscopy (PEEM), structural characterization of materials using Raman spectroscopy techniques (Raman, Resonant Raman and Surface Enhanced Raman scattering). MH will perform XPS and Raman analyses and data processing and interpretations in the framework of the WP2, WP3 and WP4 (regarding the Fabrication and Physico-chemical Characterization of Implant-type Coatings prior to and post Biological Testing) work packages.

Irina Zgura (IZ), Physicist, PhD in Physics since 2011: has a rich experience in materials physics, contact angle and surface energy measurements. IZ will perform surface energy measurements in the framework of the WP2 and WP3 (regarding the Fabrication and Physico-chemical Characterization of Implant-type Coatings).

Cristina Popa (CP), Physicist, PhD student since 2014: performed the PhD thesis studies in the field of synthesis and physico-chemical characterization of bioceramic materials with antimicrobial activity for medical applications. CP will imply progressively during the project in the WP2, WP3 (regarding Fabrication and Physico-chemical Characterization of Implant-type Coatings) and WP4 (regarding the Antimicrobial Activity Studies) work packages.

Nicolae Taina (NT), Doctor of Medicine, Clinical Pharmacology Specialist, MSc in the field of Bioengineering, PhD student in the field of Pharmacology since 2014. The PhD student will participate in the in vivo studies (WP5). The project will benefit from his expertise in pharmacology; also NT will have the chance to be actively involved in an in vivo study implying complex wounds and healing processes.

Marius Necsulescu (MN), Doctor of Veterinary Medicine, with a Specialization in Microbiology, PhD since 1996: is a Research Scientist – Grade I, with a long and fruitful experience in producing vaccines and sera, will conduct and participate in the in vivo study (WP5), and in the antimicrobial activity testing for the BG implant surfaces (WP4).

Catalin Radulescu (CR), Electronics and Vacuum Technician: will assure the maintenance of deposition systems and some of the characterization facilities. CR will be also involved in the WP2 activities regarding the Fabrication of Implant-type Coatings and RF-MS deposition system Adaptation in view of Increasing Productivity.

Results delivered in 2015 – 2017 period:

Novel bioactive glass powder materials: synthesis and multi-parametrical characterization;
Selection of the best bioactive glass formulation with optimal antimicrobial and cytocompatibility response;
Bioactive thin coatings deposited by magnetron sputtering starting from the optimized compositional system. Fabrication, physical-chemical characterization, mechanical and biological functional testing;
Technological algorithms for coating uniformly real dental implants with complex geometry;
New steps toward implementing the technological bioglass biofunctionalization recipes to micro-production level;
Publication of scientific articles in ISI-Web of Science indexed journals with high visibility.

2015: SYNTHETICAL SCIENTIFIC REPORT no. 1 in .pdf format available at UEFISCDI;
2016: SYNTHETICAL INTERMEDIARY SCIENTIFIC REPORT in .pdf format available at UEFISCDI;
2017: SYNTHETICAL FINAL SCIENTIFIC REPORT in .pdf format available at UEFISCDI.

Web of Science® articles - published or accepted:

01. A.C. Popa^, G.E. Stan*^,^, C. Besleaga^, L. Ion, V.A. Maraloiu, D.U. Tulyaganov, J.M.F. Ferreira*, Submicrometer hollow bioglass cones deposited by radio frequency magnetron sputtering: Formation mechanism, properties, and prospective biomedical applications; ACS APPL MATER INTER 8 (2016) 4357–4367. http://dx.doi.org/10.1021/acsami.6b00606.
02. A.I. Bita, G.E. Stan^, M. Niculescu*, I. Ciuca, E. Vasile, I. Antoniac, Adhesion evaluation of different bioceramic coatings on Mg-Ca alloys for biomedical applications; J ADHES SCI TECHNOL 30 (2016) 1968–1983. http://dx.doi.org/10.1080/01694243.2016.1171569.
03. A.C. Popa^, G.E. Stan*^,^, M.A. Husanu^, I. Mercioniu, L.F. Santos, H.R. Fernandes, J.M.F. Ferreira*, Bioglass implant coatings interactions in synthetic physiological fluids with varying degrees of biomimicry; INT J NANOMED 12 (2017) 683–687. http://dx.doi.org/10.2147/IJN.S123236.
04. L. Duta, N. Mihailescu, A.C. Popescu, C. Luculescu, I.N. Mihailescu*, G. Çetin, O. Gunduz, F.N. Oktar, A.C. Popa^, A. Kuncser, C. Besleaga^, G.E. Stan*^,^, Comparative physical, chemical and biological assessment of simple and titanium-doped ovine dentine-derived hydroxyapatite coatings fabricated by pulsed laser deposition; APPL SURF SCI 413 (2017) 129–139. http://dx.doi.org/10.1016/j.apsusc.2017.04.025.
05. A.C. Popescu, P.E. Florian, G.E. Stan*^,^, G. Popescu-Pelin, I. Zgura^, M. Enculescu, F.N Oktar, R. Trusca, L.E. Sima, A. Roseanu, L. Duta*, Physical-chemical characterization and biological assessment of simple and doped biological-derived hydroxyapatite thin films for a new generation of metallic implants; APPL SURF SCI 439 (2018) 724–735. https://doi.org/10.1016/j.apsusc.2018.01.008.
06. B.W. Stuart*, C.A. Grant, G.E. Stan^, A.C. Popa^, J.J. Titman, D.M. Grant, Structural characterisation and mechanical performance of gallium incorporated phosphate based glasses in bulk and thin film form; J MECH BEHAV BIOMED MATER 82 (2018) 371–382. https://doi.org/10.1016/j.jmbbm.2018.03.041.
07. A.C. Popa^, H.R. Fernandes, M. Necsulescu, C. Luculescu, M. Cioangher, V. Dumitru, B.W. Stuart, D.M. Grant, J.M.F. Ferreira*, G.E. Stan*^,^, 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.

OSIM Patent:

01. G.E. Stan*^,^, A.C. Popa^, C. Besleaga Stan^, V. Dumitru, C. Radulescu^, Method to fabricate osteointegrative implants coated with bio-active glass layers synthesized in magnetron plasma; OSIM patent RO132595 / published in BOPI no. 5/2019.

International Conferences:

01. L. Duta, G.E. Stan^, A.C. Popa^, A.C. Popescu, Functionalization of ultra-high molecular weight polyethylene acetabular cups with bioactive glass coatings synthesized by pulsed laser deposition, EMRS Spring Meeting, 2 – 6 May 2016, Lille, France (poster presentation).
02. G.E. Stan^, A.C. Popa^, C. Besleaga^, L. Ion, V.A. Maraloiu, D.U. Tulyaganov, J.M.F. Ferreira, Formation of bioglass hollow sub-micron cones by magnetron sputtering and their prospective biomedical applications, „ALD for Novel Sensors and Biosensors" Workshop, 11 – 12 May 2016, Magurele, Romania (oral presentation).
03. G.E. Stan^, A.C. Popa^, M.A. Husanu^, M. Enculescu, C. Tanase, J.M.F. Ferreira, Dental implant fixtures bio-functionalized with mechanically resistant and cytocompatible bioglass coatings by magnetron sputtering technique, „International Workshop of Materials Physics” Workshop, 23 – 25 May 2016, Magurele, Romania (oral presentation).
04. G.E. Stan^, Compative in vitro behavior of bioglass coatings in simulated body fluid media with improved biomimicry, University of Nottingham, Faculty of Engineering, 29 July 2016, Nottingham, UK (invited lecture).
05. G.E. Stan^, A.C. Popa^, V.M.F. Marques, A.C. Galca, M.A. Husanu^, M. Enculescu, C. Tanase, D.U. Tulyaganov, J.M.F. Ferreira, Mechanical and in vitro biological performance of bioglass coatings deposited by magnetron sputtering on dental implant fixtures, Conferinta ICPEPA-10, 29 August – 2 September 2016, Brasov, Romania (poster presentation).
06. A.C. Popa^,*, G.E. Stan^, C. Besleaga^, M. Necsulescu^, H.R. Fernandes, J.M.F. Ferreira, Antibacterial efficiency of alkali-free biocompatible glasses additivated with ZnO and/or SrO active agents, European Ceramics Society (ECerS) Conference, 9 – 13 July 2017, Budapest, Hungary (poster presentation).
07. G.E. Stan^^,*, A.C. Popa^, H.R. Fernandes, J.M.F. Ferreira, The prospects for bio-glass implant coatings, European Ceramics Society (ECerS) Conference, 9 – 13 July 2017, Budapest, Hungary (invited lecture).

*corresponding 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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