TE 43 / 2011 En

Project name: Antimicrobial and degradable biohybrid substrates with controlled surface architecture combining localized bio activation with antifouling properties

Subprogram: Research projects for the stimulation of the forming of young independent research teams

Contracting authority: Executive Agency for Higher Education, Research, Development and Innovation Funding

The choice of polymeric materials as platform for cell regeneration and the patterning methods are the key point in realizing hybrid complex supports with superior properties targeting the adhesion and cell manipulation activity. Within this context, the project objective is the realization of antimicrobial, biocompatible and degradable bio-hybrid scaffolds/substrates with controlled designed surface architecture and chemistry.

The project novelty relies on combining the advantages offered by specific properties of naturally derived and synthetic polymers (i.e controlled degradability, specific activation) with the ones offered by laser based methods (i.e. localized transfer, flexibility, clean techniques, no prior pretreatment of materials).

The novel approach within this project aims obtaining hybrid scaffolds/substrates with controlled surface architecture; and implies taking in account the advantages offered by the laser based methods (laser controlled ablation, MAPLE and LIFT) and the specific properties (antimicrobial, biocompatible and degradable) of the polymeric materials. The materials used in this project are: Polycaprolactone (PCL) used as biodegradable matrix/substrate; Polyethylene glycol (PEG) used as cell repellent substrates with antifouling properties; Chitosan used as antimicrobial factor; Collagen and laminin used as bio-activation factors.

A team of six young researchers and one senior researcher will work on addressing the afore mentioned issues by: i) processing of bio-hybrid structures by spin coating and Matrix Assisted Pulsed Laser Evaporation; ii) substrates controlled laser structuring and patterning by laser ablation and Laser Induced Forward Transfer; iii) enhancing the scaffold functionality by embedding naturally derived polymers (i.e. chitosan, collagen, laminin) as antimicrobial, antifouling and bio activation factors into biocompatible and degradable synthetic polymers (polyethylene glycol, polycaprolactone) and iv) evaluating of texturing and disposition of specific “architecture” substrate effect on the cellular metabolic response and proliferation.

The choice of polymeric materials, which are to be the platform for cell regeneration, and the patterning methods are the key point in realizing hybrid complex supports with superior properties targeting the adhesion and cell manipulation activity.

The general objective of our project towards the successful achievement of this class of multifunctional and complex hybrid support for cell development and manipulation studies, and therefore towards the progress beyond the scientific and technological issues is the realization of antimicrobial, biocompatible and degradable hybrid 2D and 3D scaffolds and substrates with controlled designed surface architecture and chemistry.

The controlled designed surface architecture using laser ablation and LIFT implies localization, surface topographical features, textures, geometries and shapes, porosity and roughness whilst the controlled surface chemistry implies LIFT localized transfer in specially designed geometry of bio activation factors.

The novelty of the project relies on combining the advantages offered by specific properties of naturally derived and synthetic polymers (i.e controlled degradability, specific activation, antimicrobial) with the ones offered by laser based methods (i.e. possibility of specific localized transfer, flexibility in processing various materials in a controlled manner, clean techniques, no prior pretreatment of materials necessary).

Scientific results:

Polymeric materials, both synthetic (PCL, PEG or PEO) and natural (collagen, Chitosan, Laminin), were used in combination with laser based methods(MAPLE, LIFT) to obtain multifunctional hybrid complex supports targeting controlled cell adhesion and cell manipulation activity.

Antimicrobial, biocompatible and degradable hybrid 2D (ditches, holes, fingerprint like) and 3D scaffolds (bubble like, sponge like) and substrates with controlled designed surface architecture and chemistry were obtained.

The controlled designed surface architecture was realized by direct laser ablation and LIFT. This aspect implied specific localization, surface topographical features, textures, geometries and shapes, porosity and roughness whilst the controlled surface chemistry implies LIFT localized transfer in specially designed geometry of bio activation factors.

1. V. Dinca, L. Rusen, M. Dinescu, Matrix Assisted Pulsed Laser Evaporation of biopolymers using 266 nm for biomedical applications, ROMOPTO 3-6 sept 2012, Bucharest, Romania

2. L. Rusen, V. Dinca, C. Mustaciosu, M. Dinescu, Effective method for polymeric materials patterning for cell behavior studies, ROMOPTO 3-6 sept 2012, Bucharest, Romania

3. L. Rusen, V. Dinca , C. Luculescu, M. Filipescu, M. Zamfirescu and M. Dinescu, Morphological characteristics of chitosan based structures obtained by femtosecond laser methods, EMRS 2012, Strasbourg, France

4. V. Dinca, C. Mustaciosu, A. Palla-Papavlu, L. Rusen, B. Mitu, M. Filipescu , M. Dinescu, Protein-Resistant Polymer Coatings obtained by Matrix Assisted Pulsed Laser Evaporation, EMRS 2012, Strasbourg, France

5. Dinca V., Rusen L., A. Palla Papavlu, A. Matei, V. Ion and M. Dinescu, Polymer Multilayer obtained by Matrix Assisted Pulsed Laser Alternative Evaporation, EMRS 2012, Strasbourg, France

6. V. Dinca, T. Mattle A. Palla Papavlu, M. Filipescu, M. Dinescu, , A. Wokaun, T. Lippert, Polymer micro and nanopatterning using laser transfer onto soft substrates assisted by a dynamic release layer, EMRS 2012, Strasbourg, France

7. Laurentiu Rusen, Marian Zamfirescu, Catalin Luculescu and Valentina Dinca, International conference of Student Chapter Photoniscs, ISCP, mai, 2012, Sinaia, Morphological Changes on the Surface of Polymer Films Induced by Femtosecond
Laser Irradiation

8. V. Dinca, A.Palla-Papavlu, M. Filipescu, L. Rusen, T.Lippert, M. Dinescu, LIFT and MAPLE Methods for Obtaining Multicomponent Protein-Polymer Patterns with Controlled Cell Binding Properties, 12th International Conference on Laser Ablation, October, 6th-11th, 2013, Ischia (Italy)- poster presentation P3-61 COLA 2013

9. P. Florian, V. Dinca, L. Sima, L. Rusen, M. Dinescu, R. Evans, A. Roseanu, Lactoferin-Cispaltin-Embedded Biodegradable Polymeric Thin Films With Antitumoral Activity in Vitro, International BioIron Society Program, University College London, April 14 - 18, UK - poster presentation BioIron2013-P52

10. V. Dinca, L. Rusen, C. Mustaciosu and M. Dinescu, Protein Absorption and Cell Attachment on copolymer thin films obtained by MAPLE Modern Laser Applications - INDLAS 2013, Bran, 20 - 24 May, Romania - poster presentation INDLAS2013

11. L. Rusen, V. Dinca, C. Mustaciosu, M. Zamfirescu, and M. Dinescu, The study of the influence of biopolymer patterns on cell behavior in vitro, Modern Laser Applications - INDLAS 2013, Bran, 20 - 24 May, Romania - poster presentation INDLAS2013

12. V. Dinca, L. Rusen, A. Palla-Papavlu, C. Mustaciosu, B. Mitu, M. Filipescu and M. Dinescu, Matrix assisted pulsed laser evaporation (MAPLE) of bioactive factors for stimulated cell adhesion interfaces, European Materials Research Society EMRS2013, 27-31 May, Strasbourg - poster presentation VPI31_EMRS2013

13. L. Rusen, M. Filipescu, V. Dinca and M. Dinescu,Stimuli responsive functional polymeric thin films obtained by matrix assisted pulsed laser evaporation (MAPLE) for cell detachment studies European Materials Research Society EMRS2013, 27-31 May, Strasbourg - poster presentation Best Poster Award Symposium V VPI33_EMRS2013

14. L. Rusen, V. Dinca, C. Luculescu, M. Filipescu, C. Mustaciosu, M. Bacalum, M. Zamfirescu, M. Dinescu , Tailored topography control of biopolymer surfaces by ultrafast lasers for cell - substrate studies, European Materials Research Society EMRS2013, 27-31 May, Strasbourg - poster presentation VPII28_EMRS2013

15. L. Rusen, V. Dinca , A. Palla Papavlu, C. Luculescu, M. Filipescu, L. Sima, A. Roseanu, T. Lippert and M. Dinescu, Micro-/nano-engineering surfaces using laser based methods for directing cell behavior at the cell–biomaterial interface in vitro, ISCP, 2014, Orastie, Romania

16. M. Icrivezi, J. Banita, V. Dinca, E Siringil, K. Bohlen, K.Wasmer, M. Dinescu, P. Hoffmann, A. Roseanu , Inflammatory response of laser micro- structured surfaces, ICPAM-10, 21-28 septembrie, Iasi, Romania

17. V. Dinca, P.Alloncle, P.Delaporte, L. Rusen, C. Mustaciosu, V. Ion, M. Bacalum, M. Dinescu, Antimicrobial and degradable biohybrid substrates with controlled surface architecture, ICPAM-10, 21-28 septembrie, Iasi, Romania

18. V. Dinca, L. Sima, E. Siringil, K. Bohlen, K. Wasmer, M. Dinescu, P. Hoffmann Topographical cues for modulating Mesenchymal stem cells fate, , ICPAM-10, 21-28 septembrie, Iasi, Romania

19. L.E. Sima, V. Dinca*, L. Rusen, M. Cazan, M. Chiritoiu, A. Palla-Papavlu, M. Dinescu, Combined micro- and nanoscale topography on Zirconia surfaces modulates human mesenchymal stem cells growth and cell nuclei alignment, 26-30 mai , EMRS, Lille, Franta, Symposium JP.XI 19, EMRS, Lille, Franta, 2014

20. V. Dinca, P. Florian, M. Icrivezi, L. Rusen, A. Palla-Papavlu, A. Roseanu and M. Dinescu, Hybrid and biodegradable polymeric thin films effect on murine melanoma B16-F10 cells, 26-30 mai , EMRS, Lille, Franta, Symposium NPII 11_EMRS, 2014

1. L.Rusen, M.Cazan, C.Mustaciosu, M.Filipescu, S.Sandel, M.Zamfirescu, V.Dinca, M.Dinescu, Tailored topography control of biopolymer surfaces by ultrafast lasers for cell - substrate studies, Applied Surface Science, Volume 302, 30 May 2014, Pages
256-261

2. L.Rusen, V.Dinca, B.Mitu, C.Mustaciosu, M.Dinescu, Temperature responsive functional polymeric thin films obtained by Matrix Assisted Pulsed Laser Evaporation for cells attachment-detachment study, Applied Surface Science, Volume 302, 30 May
2014, Pages 134-140

3. V.Dinca, P.E.Florian, L.E.Sima, L.Rusen, C.Constantinescu, R.W.Evans, M.Dinescu, A.Roseanu, MAPLE-based method to obtain biodegradable hybrid polymeric thin films with embedded antitumoral agents, Biomedical Microdevices; February 2014, Volume 16, Issue 1, pp 11-21

4. L.Rusen, C.Mustaciosu, B.Mitu, M.Filipescu, M.Dinescu, V.Dinca, Protein-Resistant Polymer Coatings obtained by Matrix Assisted Pulsed Laser Evaporation, Applied Surface Science DOI: 10.1016/j.apsusc.2013.01.109, Volume 278, 1 August 2013, Pages 198-202.

5. V.Dinca, T.Mattle, A.Palla-Papavlu, L.Rusen, C.Luculescu, T.Lippert, M.Dinescu, Polyethyleneimine patterns obtained by laser-transfer assisted by a Dynamic Release Layer onto Themanox soft substrates for cell adhesion study, Applied Surface Science DOI: 10.1016/j.apsusc.2013.02.052, Volume 278, 1 August 2013, Pages 190-197.

6. M. Cazan, V. Dinca, M. Dinescu, C. R. Popescu, Zirconia, a wonderful material, practica Medicala – VOL. IX, NR. 2(34), AN 2014