Enhancement of bone defect repair by mussel-inspired TiO2-based nanostructures functionalized with bioactive phytomolecules
Prof. Dr. Habil. Anisoara Cimpean
Phone number: 021.318.15.75/int 106
Fax: 021.318.15.75/int 102
University of Bucharest
Faculty of Biology, Department of Biochemistry and Molecular Biology
Partners involved in the project:
P1 – Polytechnic University of Bucharest
Contractual authority: UEFISCDI
Project code: PN-III-P2-2.1-PED-2016-1372
Project type and number: PED-149/2017
Project title: Enhancement of bone defect repair by mussel-inspired TiO2-based nanostructures functionalized with bioactive phytomolecules
Duration: 18 months
Budget: 600.000 lei
Despite the vast development and clinical use experienced by the metal implants, such as titanium (Ti), these are far from optimal. The scientific knowledge about tissue-implant interactions, as well as recent advances in regenerative medicine raises a new concept of biomaterials. The use of bioactive coatings is one of the most promising strategies to promote appropriate surface-cell interactions at the implantation sites. In this context, the project scope is to immobilize bioactive phytomolecules of Herba Epimedii (EpFs) with osteoprotective effect on Ti surfaces nanostructured with TiO2 nanofibers and nanotubes via polydopamine (PDA) and nitrodopamine (NDA) films as intermediate layers, and to investigate how such surface functionalization would affect the MC3T3-E1 osteoblasts behavior and inflammation responses of RAW264.7 cells. This mussel inspired surface functionalization strategy is extremely useful for biomaterial applications because it does not require the time-consuming synthesis of complex linkers and the process is solvent free and non-toxic. Finally, in vivobiological performance of the developed coatings will be assessed.
Our belief is that this technology provides an easy, economic, and specific approach for the future rational design of implantable medical devices with desired tissue reactivity and, hopefully, wound healing capability. According to our knowledge, at national level, there are no other research groups involved in modifying metallic surfaces with PDA or NDA as bio adhesives. The novelty of the project reveals especially in combining the nanostructure of Ti substrate by deposition of TNF and TNT with PDA and NDA coatings functionalized with EpF representatives and in demonstration of the feasibility of this technological approach by surface characterization and in vitro and in vivo studies.
Project coordinator (CO) will be involved in the validation of the technology of PDA and NDA coatings and immobilization of EpFs by in vitro and in vivo studies. The research team has qualification and relevant experience in cellular biology for investigation of the cell response to the presence of implantable biomaterials including biomaterials with modified surface as results from certain publications in cooperation with Partner 1 (P1).
The main objective of the proposed project is the grafting of Epimedium derived flavonoids (EpFs) on TNF and TNT via intermediate PDA and NDA layers in order to induce a favorable osseointegration.
The specific objectives of this project are:
- Obtaining of nanostructured Ti surfaces, deposition of PDA- and NDA- based films and EpF immobilization;
- Characterization of PDA, NDA and PDA-EpF, NDA-EpF films deposited on Ti surfaces nanostructured with TNF and TNT;
- Evaluation of in vitro biological performance of the elaborated un-functionalized and EpF- functionalized PDA- and NDA- based films;
- Obtaining of the demonstrator product (EpF functionalized PDA- / NDA- coated Ti/TiO2 pins);
- Development of an in vivo experimental model for osseointegration of the demonstrator product.
Thus, our starting point is a TRL 2 which represents a concept – DA is a bioadhesive. We have already verified this concept using a well-established procedure and now we take the advantages of this property for bonding EpFs and to test a related bioadhesive (NDA) from the same class. After implementation of the starting concept, this will be developed and validated from next points of view: physico-chemical surface properties and biological performance in order to prove the bioactivity and feasibility of the coating and functionalization technologies which correlates with a TRL 3.
Expected results of the project are:
- Obtaining the demonstrator product – EpF-functionalized PDA-/ NDA- coated Ti/TiO2 pins – its bioperformance will be proved by advanced in vitro and in vivo biological assays;
- Elaboration and validation of technologies related to surface coating and functionalization procedures;
- Dissemination of the project results through a web page, by which stakeholders will be informed about project progress;
- Elaboration of 2 Master theses.
Participation to international scientific reunions
Popescu, S., Pirvu, C., Dumitriu, C., Cimpean, A. Bioinspired functionalization of Ti surface with natural active agents. International Conference on Mechanical, System and Control Engineering (ICMSC 2017), 19-21 May 2017, St. Petersburg, Rusia (oral presentation). Conference Abstracts, p. 18.
Pirvu, C., Popescu, S., Dumitriu, C., Titanium surface modification by mussel-inspired adhesion of antioxidants, International Conference on Mechanical, System and Control Engineering (ICMSC 2017), 19-21 May 2017, St. Petersburg, Rusia, Conference Abstracts, (oral presentation).
Ion, R., Mitran, V., Polipciuc, W., Neacsu, P., Popescu, S., Necula, M.G., Pirvu, C., Cimpean, A. In vitro assessment of cellular response to icariin-functionalized TiO2 nanotubes designed to promote bone regeneration, RICCCE 20 – 20th Romanian International Conference on Chemistry and Chemical Engineering, Poiana Brasov, Romania, 6-9 September 2017 (oral presentation).
Polipciuc, W., Popescu, S., Dumitriu, C., Ion, R., Mitran, V., Albu, A.-M., Prodana, M., Cimpean, A., Pirvu, C. Functionalization of Ti surfaces with bioactive phytomolecules of Herba Epimedii with osteoprotective effect, RICCCE 20 – 20th Romanian International Conference on Chemistry and Chemical Engineering, Poiana Brasov, Romania, 6-9 September, 2017 (poster presentation).
Participation to national scientific reunions
Necula, M.G., Ion, R., Drăghicescu, W.M., Mitran, V., Popescu, S., Câmpean, A. Inflammatory response evoked by TiO2 nanostructures functionalized with icariin, The 36th Annual Scientific Session of the Romanian Society for Cell Biology and the 10th National Congress with international participation, Craiova, România, 6-9 June, (poster presentation).
M. Albu, W. Polipciuc, T. Munteanu, R. Ion, V. Mitran, A. Câmpean, S. Popescu, C. Pirvu. Nitrodopamine vs. dopamine as an intermediate layer for bone regeneration applications, original article submitted to Journal of Materials Chemistry B.
Ion, M.G. Necula, V. Mitran, P. Neacşu, A. Câmpean. Drug delivery systems based on titania nanotubes and active agents for enhanced osseointegration of bone implants, review article submitted to Current Medicinal Chemistry. Status: under review.
PhD/Master/Bachelor Theses on project’s topics
Wanda Polipciuc (Draghicescu) (Politehnica University of Bucharest): Bioactive coatings based on TiO2nanostructures functionalized with phytomolecules (2018-2021).
Disertation (Master) Thesis:
Negrescu Andreea Mariana (University of Bucharest): The cellular response to icarrin-functionalized nanostructured TiO2 surfaces (2018).
Maria Zarif (Politehnica University of Bucharest): Hybrid nanostructured coatings for modification of the implantable titanium surfaces (2018).