Antitrombojenik Nanokompozit Kalp Kapakçık Malzemelerinin Geliştirilmesi

Abstract

The aim of the thesis is to develop composite scaffolds with antithrombogenic properties and high blood compatibility by modifying decellularized pericardial tissue with carboxylated carbon nanotubes and to characterize these structures for use in heart valve tissue engineering applications. In this study, it is aimed to contribute to the prevention of thrombogenicity and low mechanical strength problems that occur in mechanical and bioprosthetic heart valves currently used in heart valve replacement surgeries, thus avoiding the need for repeat heart valve surgeries and the use of lifelong anticoagulant drugs. In this context, bovine-derived pericardial tissues were used and the appropriate decellularization protocol was optimized, then composite tissue scaffolds were prepared by modifying the decellularized pericardial tissue surfaces with carboxylated (-COOH) multi-walled carbon nanotubes. In the first part, decellularization studies were carried out by using physical methods such as freeze-thaw and chemical methods such as sodium dodecyl sulfate (SDS), Triton-X-100 alone or in combination for decellularization optimization. In addition, the effect of different concentrations of chemical agents on decellularization success was investigated. Then, histology analyzes were performed with Hematoxylin & Eosin, DAPI and Masson's Trichrome stainings. Biochemical characterization studies were also performed with PicoGreen, dimethyl methylene blue (DMMB) and hydroxypyrrole kits. As a result of these studies, the appropriate decellularization group was determined as a combination of freeze-thaw and 0,5% (w/v) SDS agent. The untreated and optimized decellularized groups were analyzed by thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Fourier transform infrared spectrometry (FTIR), atomic force microscopy (AFM), mechanical analysis and differential scanning calorimetry (DSC), thus scaffolds were morphologically, thermally and mechanically characterized. In the second part of the thesis, decellularized bovine pericardial tissues were treated with different concentrations of carboxylated carbon nanotube solutions and composite tissue scaffolds were obtained. The success of the pericardium and carbon nanotube interaction was characterized by thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Fourier transform infrared spectrometry (FTIR) and atomic force microscopy (AFM). Platelet adhesion test, Calcein-AM staining, kinetic blood coagulation, hemolysis and cytotoxicity analyzes were performed for blood compatibility and thrombogenicity evaluations by choosing the two carbon nanotube concentrations with the highest interaction rate. Apart from these, the effect of carbon nanotube modification on mechanical strength and thermal stability were investigated by mechanical analysis and differential scanning calorimetry (DSC). The two composite scaffolds studied showed similar results in blood compatibility and antithrombogenicity assessments and were successful compared to untreated and decellularized scaffolds.