Funkcionalizacija biomedicinskih vzorcev s termodinamsko neravnovesno plinsko plazmo (Slovene)

Systematic research on modification of surface properties of biomedical samples will be performed in order to elaborate a method for improvement of hemocompatibility of hearth valves. Several different approaches to surface modification of heart valves will be tested thoroughly: i) super-hydrophilization by making the surface nanorough and rich with polar functional groups, ii) functionalization by non-equilibrium gaseous plasma followed by deposition of hemo-compatible coatings, iii) incorporation of sulfated functional groups, iv) deposition of multilayer graphene sheets followed by grafting with super-hydrophilic coating, and v) endothelization of heath valves modified by above mentioned procedures. The functionalization procedures will be optimized in terms of best plasma parameters that allow for stable surface modification. Gaseous plasma with adjustable flux of chemically reactive radicals will be created in gases such as H2S, SO2, NH3 and O2. Appropriate nanorough surface with dense nanocones with a typical dimension of 50 nm and a high aspect ratio will be prepared using extremely selective plasma etching, the technique that has been elalborated in our labs for other materials recently. Neutral reactive gaseous particles will be used instead of ions in order to achieve almost perfect etching selectivity. Multilayer graphene sheets will be deposited perpendicular to the samples surface and modified by several subsequent treatments in order to obtain super-hydrophilic surface with dense nanowalls with gaps between the walls of the order of 10 nm. This procedure will be protected by a patent application. The majority of experiments will be performed on model samples and the most promising ones in terms of improved hemocompatibility will be repeated on heart valves. Apart from extensive biomedical tests, sophisticated methods for real time monitoring of plasma parameters will be applied together with standard techniques for surface and thin film characterization such as high resolution XPS, SIMS, SEM and AFM.

We managed to explan the phenomenon of extremely selective etching of polymers by highly non-equilibrium gaseous plasma treatment that leads to unexpectedly rough surface roughness with dense nanocones. The extensive research performed within this project confirmed the hypothesis that the formation of nanocones is due to non-homogeneity of the original material. In the case of vascular implants made from polymer the formation o nanocones is due to semi-crystalline nature of the material. The amorphous flase is etched at higher rate than the crystalline one what leads to nanostructuring. Furthermore, the edges of crystallites are etched preferentially so the interaction kinetics (taking into account both ions and neutral reactive particles) favorises formation of nanocones, what is definitely against the rules of equilibrium thermodynamics which favorises smooth surfaces. The ageing effects has been explained, too. The surface rich in highly polar functional groups are thermodynamically non-equilibrium so spontaneous approach to equilibrium occurs. The hypothesis was confirmed by studying ageing effects at different temperatures since we observed monotonic increase of the ageing with increasing saple temperatures. We are the first group that addressed the biocomptibility (hemocompatibility) of heart valves coated with multi-layer graphene sheets. Although graphene has become extremely popular due to the recent Nobel prize, no group worldwide has published a research on this phenomenon. Since our results are innovative and applicable in medical praxis we filed an appropriate patent application. The appropriate scientific paper will be submitted as soon as the patent application will appear in patent databases - in September 2015.

The direct impact of the proposed project is clear: our industrial partner wishes to enter a specific market niche (cardiovascular implants) which is characterized by extremely high value added. Current cost of an implant is several thousand Euro, and any production costs are simply negligible comparing to the knowledge cost. As already reported, we filed an international patent application - see Socio-economic achivement #1. The research results obtained within this project represent a solid background for further dissemination. As experienced researchers we are aware that any commercialization of scientific results can appear only after further development and thorough testing of a new product and/or technology. This is especially true for pharmaceutical and medical products that require thorough testing according to strict protocols and often last a decade if not longer. The project duration was 3 years only so any commercialization will appear only well after the project has terminated. In the next step we shall perform in-vivo tests with model animals. When (if) such experiments will confirm the results of the in-vitro tests reported in this document we shall contunue with clinical tests and if even results of such tests are as positive as expected we can foresee commerciallization of the results.