Heparin immobilization on the intravascular catheter surfaces for improving antithrombogenicity and antibacterial activity

Implantable materials are tools that are used in the human body for temporary or permanent, internal or external, treatment or repair, and so on. Nowadays, due to the growing population and long lifetime, the rate, quantity, and duration of these materials are also increasing. Therefore, implantable materials should be biocompatible with the environment in their usage area and be designed to prevent any complications after the transplant. Within the scope of this thesis, two different materials were used as polymeric and metallic substrates for surface modification with an anticoagulation drug that is used in clinics, heparin. Polypropylene (PP) was selected as a model polymeric substrate and plasma-assisted surface modification was applied in two steps: (i) oxygen etching and (ii) amine-rich functional group creation. Surface modification parameters that were held with the plasma polymerization (PlzP) technique were analyzed with contact angle measurements, surface free energy calculations, obtaining the maximum nitrogen amount on the surfaces and increasing the surface roughness values, etc., and the parameters were optimized accordingly. Immobilization of heparin applied as pure heparin (hep) and covalent bond agent assisted (hep*) with 3 different concentration values. The amount of immobilized heparin detected with toluidine blue (TB) dye and the parameter that produces the maximum amount of immobilized heparin were selected as optimal. Covalent bond formation between hep* and PP substrates was proven with amide I and II peaks, which were detected with FTIR-ATR analysis. Compared to the bare PP substrates, heparin immobilization provided a lower amount of adhered protein and much more efficient hemocompatibility testing (platelet adhesion, hemolysis, and kinetic blood coagulation rate) results. Also, the antiadhesive characteristics of heparin-immobilized PP surfaces were tested against both gram-positive and gram-negative bacteria strains, and the antibacterial mechanism of heparin was revealed as "contact killing". Lastly, the biocompatibility of produced surfaces was tested with the BJ human fibroblast cell line. On the other hand, titanium (Ti) was selected as the model metallic substrate, and heparin immobilization onto the surfaces was held in one step with the alternative current electrophoretic deposition (AC-EPD) technique. Parameter optimization was achieved with contact angle measurements, free surface energy calculations, and the surface roughness values of purely deposited heparin. In the beginning, the deposited heparin amount was detected with TB dye, but according to further analysis, this procedure is not appropriate to detect the heparin amount that was deposited with the AC-EPD technique. The effect of heparin deposition on Ti substrates was examined detailedly with adhered protein amount, hemocompatibility tests, antiadhesive characteristics, and biocompatibility, respectively. In brief, within the scope of the thesis, different surface modification techniques with heparin on both PP and Ti surfaces were examined. With the help of the anticoagulant characteristic of heparin, which is already known, also its antibacterial, antiadherent, and biocompatibility characteristics were examined in detail and brought to the literature.