Biocompatible medical implants elaborated from nitrided titanium-based superelastic alloys

Romanian coordinator:
Assoc. Prof. Anisoara Cimpean
Phone: 021.318.15.75/int 106
Fax : 021.318.15.75/int 102
E-mail: anisoara.cimpean@bio.unibuc.ro

French coordinator:
Prof. Thierry Gloriant
Tel/Fax : +33.(0)2.2323.8241/8240
E-mail : Thierry.Gloriant@insa-rennes.fr

Partners involved in the project:

•    University of Bucharest, Faculty of Biology, Department of Biochemistry and Molecular Biology, Romania 

•    INSA Rennes, ISCR UMR 6226, Metallurgical Chemistry Lab., France

•    Company AMF (SME), Lury-sur-Arnon, France

Institute of Physical Chemistry “Ilie Murgulescu”, Bucharest (subcontracting institution)


Romanian Contractual Authority: UEFISCDI

French Contractual Authority: ANR

Project code: PN-II-ID-JRP-2012

Project type and number: PN-II-ID-20-RO-FR-2014

Project title: Biocompatible medical implants elaborated from nitrited titanium-based superelastic alloys

Acronym: BIOMIMETIS

Duration: 36 months

Budget allocated by UEFISCDI: 250 000 €

Total project budget: 502 474 €


Summary:
Organs like bone and vessels have a limited capacity for self-repair, and after injury or disease the regenerative power of adult tissue is often not sufficient, leading to non-functional scaring. Despite the vast development and clinical use experienced by the metal implants during the last decades these are far from optimal. The objective of the present BIOMIMETIS project is to design and characterize new highly biocompatible titanium -based alloys for implantable devices in human body. In order to overcome the limited lifespan of the currently used biomedical alloys, the proposed project envisages gas-nitriding treatments of recently developed Ni-free superelastic alloys (Gum-metal Ti-23Nb-0.7Ta-2Zr-O, Ti-24Nb-0.5O and Ti-24Nb-0.5N alloy compositions) which will harden the surface and improve further the biocompatibility. Through a scientific and engineering program organized in 3 complementary tasks, the designed Ni-free nitrided superelastic titanium-based alloys will be deeply characterized to evaluate their functionalities for targeted biomedical applications. The fabrication of bone staple and endovascular stent prototypes by the industrial partner is envisaged as proof of concept in this proposal. It is expected that the new Ti-based alloys will show excellent biocompatibility, high corrosion resistance in SBF and desirable mechanical properties combining the bulk superelastic property and the hard and wear resistant surface. These properties are particularly appreciated for various medical devices and, particularly, for targeted biomedical applications such as cardiovascular stents and orthopaedic bone staples. Furthermore, our expectations are that positive osteoblast response, a better endothelialization and a reduced inflammatory response will be obtained on the corresponding TiN-coated surfaces.

Objectives:
Within the frame of the proposed project the specific objectives are:
i) the deposition of TiN on the newly developed superelastic Ti-based alloys by gas-nitriding method (scientific novelties)

ii) material characterization which will be approached from next points of view:
1. Comparative microstructural, chemical, crystallographic, physical and mechanical characterization of coated and un-coated alloys (original results);
2. Fabrication of the bone staple and endovascular stent prototypes by AMF company (industrial application);
3. The chemical, morphological, electrochemical characterization of the coated alloys’ surfaces before and after soaking in simulated body fluid (scientific novelties);
4. Evaluation of the fatigue behaviour of biomedical dispositives (original results).

iii) biocompatibility testing which will consist of:
1. Cytotoxicity evaluation of the test materials (original results) and in vitro studies concerning the interactions of the osteoblastic type cells with materials’ surfaces (original results);
2. In vitro study to investigate the suitability of uncoated and N-coated superelastic Ti alloys for stent application by studying the endothelial cell behavior (scientific novelties).
3. To compare the material surface population with endothelial progenitor cells (EPCs) and cell behaviour on bare and N-coated superelastic Ti in order to prove their suitability for stent application in the form of metallic bare stents or stents seeded with the EPCs (a potential new avenue opened by completion of this project)

iv) At industrial level, cooperation work will be focused on fabrication of stent and staple prototypes in order to apply designed technologies for industrial application.

Research team

Name and surname

Position in the project

Cimpean Anisoara

Project director/Senior researcher II

Ion Raluca

Young researcher III

Mitran Valentina

Research assistant

Neacsu Patricia

Research assistant (phD student)

Staras Adela

phD student

Serban Mirela

Research assistant

Estimated results:

-dissemination of project results in ISI indexed journals;

-dissemination of project results at national and international conferences with high scientific impact;

-elaboration of 1 PhD and 2 Master theses.

ARTICLES

Ion R, Luculescu C, Cimpean A, Marx P, Gordin D-M, Gloriant T. Nitride coating enhances endothelialization on biomedical NiTi shape memory alloy. Mater Sci Eng C, 62, 686–691 (2016). http://www.sciencedirect.com/science/article/pii/S0928493116301217

Castany P, Gordin D-M, Drob SI, Vasilescu C, Mitran V, Cimpean A, Gloriant T. Deformation mechanisms and biocompatibility of the superelastic Ti–23Nb–0.7Ta–2Zr–0.5N alloy. Shap Mem Superelasticity, 2, 18-28 (2016). http://link.springer.com/article/10.1007/s40830-016-0057-0

Mitran V, Vasilescu C, Drob SI, Osiceanu P, Calderon-Moreno JM, Tabirca MC, Gordin DM, Gloriant T, Cimpean A. Biological behaviour and enhanced anticorrosive performance of the nitrided superelastic Ti-23Nb-0.7Ta-2Zr-0.5N alloy. BioMed Res Int, 125, Article ID 261802, http://dx.doi.org/10.1155/2015/261802 (2015).

Drob SI, Vasilescu C, Calderon Moreno JM, Osiceanu P, Neacsu P, Cimpean A, Gordin DM, Gloriant T. Multifunctional "gum metal" titanium-based alloy: Its long-term electrochemical behaviour and macrophage response. Int J Electrochem Sci, 10, 10738-10755 (2015).


Communications to scientific reunions:

     1.D.M. Gordin, D. Busardo, A. Cimpean, C. Vasilescu, D. Hoche, S.I. Drob, V. Mitran, M. Cornen, T. Gloriant. Biocompatibility enhancement of a Ni-free superelastic titanium alloy by ion implantation. International Conference on Martensitic Transformations (ICOMAT), july 2014, Bilbao, Spain – prezentare poster. 

     2.D.M. Gordin, D. BusardoA. Cimpean, E. Vasilescu, D. Höche, T. Gloriant. Nitruration par implantation ionique d'un nouvel alliage de titane superélastique pour des applications biomédicales. Matériaux 2014, nov 2014, Montpellier, France - prezentare orala.
     
     3. T. Gloriant, D.M. Gordin, P. Castany, C. Vasilescu, A. Cimpean. Potentiality of the metastable beta titanium alloys for biomedical applications. 15th International Conference on Rapidly Quenched and Metastable Materials (RQ15), aug 2014, Shangai, China.

     4. T. Gloriant, D.M. Gordin, P. Castany, C. Vasilescu, A. Cimpean. Potentialities of the metastable beta titanium alloys for biomedical applications. Architectured Biomaterials, Medical and Tissue Engineering Symposium, French Embassy in Berlin, dec 2014, Germany - invited lecture.

    5. A.I. Staras, R. Ion, D.M. Gloriant, A. Cimpean, O. Zarnescu. The effects of nitriding treatment of nitinol on endothelial cell behavior. International Seminar on Biomaterials & Regenerative Medicine, BIOREMED 2015, Felix-Bath, Oradea, 17-20 sept, p. 166 - prezentare poster.

     6. A.I. Staras, V. Mitran, A. Cimpean, O. Zarnescu. In vitro biocompatibility assessment of the superelastic beta titanium alloy, Ti-23Nb-0.7Ta-2Zr-0.5N, with nitrided surface. Scientific communication session of the students from Faculty of Biology, Bucharest, 25 mai 2015, p.50 - oral presentation.

7. D.M. Gordin, Y. Bedouin, V. Mitran, A. Cimpean, C. Vasilescu, S.I. Drob, L. Heraud, T. Glorian. Surface nitriding of b-type titanium-based superelastic alloys for biomedical applications. International Conference on processing & manufacturing of advanced materials processing, fabrication, properties, applications (THERMEC 2016), 29 may-3 june, Graz, Austria, p. 202-203 - invited presentation.

PhD thesis on project's topic:

Staras Adela- In vitro biological performance assessment of surface-modified biomaterials (2014-2017)

Master thesis on project's topic:

Noana Doinita- In vitro studies of the osteoblast response to nitrided super-elastic beta-type titanium alloys (2014-2015)

Last updated at: December 05, 2016.