Spaced TiO2 nanotubes as platforms for drug delivery and bone regeneration

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Project leader:

Prof. Dr. Habil. Anisoara Cimpean

Phone number: 021.318.15.75/int 106

Fax: 021.318.15.75/int 102

E-mail: anisoara.cimpean@bio.unibuc.ro

Institution: University of Bucharest

Faculty of Biology

Department of Biochemistry and Molecular Biology, www.dbbm.bio.unibuc.ro

Project code: PN-III-P4-ID-PCE-2016-0691

Project type and number: PCE 55/2017

Project title: Spaced TiO₂ nanotubes as platforms for drug delivery and bone regeneration

Acronym: NanoDelBone

Duration: 30 months

Budget: 850.000,00 lei

Research team:  team_members PCE-55

Abstract:

In spite of the vast development and clinical use of titanium (Ti) based metallic implants and of their gold standard status for dental/orthopedic implants, in some cases Ti implants are encapsulated in vivo by fibrous tissue and show a lack of osseointegration which can finally lead to implant failure. To improve implant viability and its biologic performance, nanotechnology and local drug delivery strategies hold certain advantages through the modification of implants’ surface. In this context, the main objective of this project is to obtain novel platforms for bone regeneration and drug delivery applications. These platforms consist of spaced titania nanotubes modified Ti (TNT) with varying characteristics, loaded with simvastatin (with and without PLGA coating) as a model drug known to promote bone tissue formation. The goal of the project is to evaluate TNT as platforms for drug delivery and bone regeneration.

In depth research, data collection and analysis are envisaged in NanoDelBone project to test the hypothesis according to which drug loaded spaced TNT will improve the quality of life of people in need of bone implants, by a potentially faster recovery and reduced risk of failure or side-effects, due to poor osseointegration. If our expectation will be fulfilled, the findings may form a good foundation for further potential clinical validation of Ti-based implants with this innovative surface design as ready products for clinical applications.

The project is built on two pillars of expertise, namely the excellent capabilities in assessment of mammalian cell – biomaterial interactions at University of Bucharest, Faculty of Biology, and the outstanding background in the electrochemical deposition of TNT and their characterization at Friedrich Alexander University, which will provide the samples to be tested. To achieve the project goals, a research team with all of the requisite expertise has been formed.

The specific objectives of the project are:

1. In vitro biological evaluation of spaced TNT;
2. Establishing the optimal dose and drug release profile;
3. Determination of spaced TNT efficacy as drug delivery vehicles through in vitro studies;
4. Determination of the in vivo therapeutic efficacy of drug loaded spaced TNT.

The expected results of the project:

• Acquiring new knowledge about the influence of spaced TNT on cells involved in bone regeneration;
• In-depth understanding of the biological effects of newly developed materials on tissue-implant interactions;
• Obtaining experimental and functional models;
• Dissemination of project results through the web page to inform stakeholders about project progress;
• Dissemination of project results through 3 ISI papers and participation to 4 international conferences;
• Elaboration of Master theses (1) and PhD theses (1).

PUBLICATIONS

ARTICLES

1. Ion, R.N., Necula, M.G., Mazare, A., Mitran, V., Neacsu, P., Schmuki, P., Cimpean, A. Drug delivery systems based on titania nanotubes and active agents for enhanced osseointegration of bone implants. Current Medicinal Chemistry, 2019. doi: 10.2174/0929867326666190726123229. IF: 3.894.
2. Necula, M.G., Mazare, A., Ion, R.N., Ozkan S., Park J., Schmuki, P., Cimpean, A. Lateral Spacing of TiO2 Nanotubes Modulates Osteoblast Behavior. Materials 2019, 12(18), 2956; https://doi.org/10.3390/ma12182956. IF: 2.972.

COMMUNICATIONS TO NATIONAL SCIENTIFIC REUNIONS

1. Necula, M.G., Neacsu, P., Staras, A. I., Cimpean A. Effect of simvastatin and some bioactive coatings on MC3T3-E1 osteoblasts. Scientific Communication Session from Faculty of Biology – 2017 Edition, Bucharest, Romania; 1 July (oral presentation).
2. Necula, M.G., Ion, R., Cimpean, A. The response of MC3T3-E1 cells to TiO2 nanotubular surfaces. Scientific Communication Session from Faculty of Biology – 2018 Edition, Bucharest, Romania; 19 May (oral presentation).
3. Necula, M.G., Ion, R. N., Ristoiu, V., Cimpean, A. In vitro inflammatory response to nanostructured TiO2 surfaces. National Conference of Doctoral Schools from Universitaria Consortium – First Edition, Iasi, Romania; 31 October – 3 November 2018 (oral presentation).
4. Necula, M.G., Mitran, V., Cimpean, A.  Effect of simvastatin and of the nanostructured surfaces on RAW 264.7 macrophages response. Scientific Communication Session from Faculty of Biology – 2019 Edition, Bucharest, Romania; 31 May (oral presentation).

COMMUNICATIONS TO INTERNATIONAL SCIENTIFIC REUNIONS

1. Cimpean, A., Neacsu, P., Mazare, A., Ion, R., Necula, M.G., Mitran, V., Schmuki, P. TiO2 nanotube surfaces as modulators of macrophage inflammatory activity. THERMEC 2018, Paris, France; 08 – 13 July (invited lecture).
2. Necula, M.G., Mazare, A., Ion, R.N., Schmuki, P., Cimpean, A. Titania nanotube spacing tunes macrophages inflammatory response. BRAMAT 2019, Brasov, Romania; 13-16 March (poster presentation).
3. Necula, M., Ion, R., Popescu, R., Marinescu, C., Cimpean, A. Effects of simvastatin and simvastatin hydroxy acid on macrophage in vitro behaviour. FEBS 2019. Krakow, Poland; 6-11 July (poster presentation).
4. Necula, M.G., Mazare, A., Ozkan, S., Trusca, R., Mitran, V., Schmuki, P., Cimpean A. Modulation of macrophage polarization by TiO₂ nanotubular surfaces. 30th Annual Conference of the European Society for Biomaterials, ESB 2019, Dresden, Germany; 9-13 September (poster presentation).
5. Necula, M.G., Mazare, A., Ion, R., Schmuki, P., Cimpean, A. Titania nanotube spacing influences in vitro cellular response. 30^th Annual Conference of the European Society for Biomaterials, ESB 2019, Dresden, Germany; 9-13 September (oral presentation).

MASTER THESIS

1. Andreea Elena Moise (2017-2019): Modulation of MC3T3-E1 pre-osteoblasts behaviour by TiO₂ nanotubes spacing.

PhD THESIS

1. Necula Madalina Georgiana (2016-2019): Spaced TiO₂ nanotubes as platforms for drug delivery and bone regeneration.

• NanoDelBone_Abstract_Phase 1
• NanoDelBone_Abstract_Phase 2
• NanoDelBone_Abstract_Phase 3