Küçük çaplı yapay damarların mevcut yetersizliklerinin iyileştirilmesi

As the world population is getting older, cardiovascular diseases are increasing correspondingly. Artificial blood vessel implantations are promising operations for bypass patients. Vascular grafts of polytetrafluorethylene (ePTFE), polyethylene terephthalate (PET) and polyurethane (PU) work well in the replacement of large diameter (>6 mm) vessels. However they fail for small diameters due to incompatibility of radial elasticity, insufficient porosity and insufficient cell growth. Considering these requirements with the large number of patients in the need of replacement grafts, the demand for an alternative small diameter graft is enormous. This thesis aims at improving inadequencies of small diameter artificial blood vessels by determining new design criterions and developing alternative construction designs as well as modification and establishment of custom designed electrospinning technology. Within this thesis, four supplementary articles were given in sequence taking the topic integrity into consideration. All articles given in seperate chapters have novelty in research and discuss remarkable and original outcomes of the thesis topic. In the first review article, after providing brief information about native blood vessels' histological and structural properties, the requirements for vascular grafts, the technology of electrospinning and the advantages of electrospun vascular grafts were introduced. The vascular graft design is accepted to be successful to the degree that it mimics the target tissue. Therefore, the design steps should be based on mimicking the native blood vessels' structural, mechanical, biological and topographical properties. In this article, the design parameters of biodegradable electrospun vascular grafts, mainly as the fiber diameter, pore size and porosity, fiber orientation, wall thickness and material selection are discussed in detail with recent literature works. Owing to the defined design criterions, multilayer designs seem to be more advantageous for vascular graft production in order to create a composite structure with differing functions and capabilities in seperate layers, as it is in native arteries. Therefore, inner layer of the vascular graft should be available for pre-endothel cell growth in order to achieve non-thrombogenicity and pore size should be limited to blood cell dimensions. On the other hand, the pore size of outer layer should be larger than the dimensions of the smooth muscle cells in order to achieve the diffusion of these cells through the wall thickness of the scaffold. Moreover, insufficient mechanical properties of this layer can be improved by achivement of radial fiber orientation as the radially oriented collagen bundles in the native vessels. Various biodegradable polymers can be used for vascular grafts' production but it is important to find the most suitable one which behaves like a stable backbone with enough mechanical integrity until it degrades and have enough elasticity to overcome radial elasticity mismatch. Therefore, the selection of material type and production technology is also important in designing a scaffold to overcome inadequencies of small diameter vascular grafts. It is intended that the blended and enriched context of this review article aims to overcome complex design problems for multilayer vascular grafts while serving a discussed literature for further studies of the thesis topic. Second article involves the optimization of selected polymer and solvent types and their electrospinning process. Among several design strategies, fiber diameter and pore size of fibrous scaffolds are one of the most determinant parameters for tissue designs; i.e. multilayer vascular grafts. Since blood vessels are composed of layered structures, pore size distribution of layers differ from each other based on cell type content and their functions in related layers. Pore size of the scaffold should enable smooth muscle cell diffusion in the middle and outer layer of native blood vessel while hindering blood leakage in the inner layer. Improved spinnability of biomaterials with differing characteristics according to desired requirements lead up design flexibility in tissue designs. Therefore, the effect of polymer concentration and addition of acids to PCL/ chloroform: ethanol solution were investigated based on solution characteristics and surface morphology of the fibrous webs including fiber diameter and pore size distribution. Moreover with Fourier Transform Infrared Spectroscopy (FTIR) analysis, residual solvent risk on produced surfaces were examined. Thesis continous with the third article on the topic of the production of single layer scaffolds for vascular grafts. Before production, basic electrospinning aparatus was modified with the requirements of vascular graft production such as 6 mm rotating type of collector for tubular scaffold production, high rotational speed motor integration to achieve radial fiber orientation, pneumatic sliding feeding unit for homogenity of the scaffold and so on. Histology of the native vessels were also observed in the context of this article to prove the discussed design parameters in first article. Taking care of these histological results, pre-mentioned design parameters and modifications of electrospinning unit, single layer scaffolds were produced. PCL in chloroform:ethanol solvent system with 18% weight ratio was chosen and predetermined electrospinning production parameters were used in the light of our previous works. Radial fiber orientation was achieved by increasing the rotational speed of the mandrel in order to improve the mechanical performance and cell organization. Fiber diameter distribution as well as pore size area and porosity analysis was examined to evaluate its suitability for cell proliferation and diffusion through the tunica media. The relationship between the orientation of fibers and cells was confirmed in vitro by seeding fibroblasts. This study aims to constitute a considerable step forward in designing multilayered vascular graft. Lastly, bilayer scaffolds were produced in the fourth article in the light of first three articles and gained experiences. In this article, PCL (in differing molecular weights) and a copolymer poly(l-lactide) caprolactone (PLC) single layer scaffolds composed of either oriented or randomly distributed fibers were produced in 6 mm tubular forms by electrospinning. Then, bilayer scaffolds from the same polymers in different combinations including randomly distributed inner layers and radially oriented outer layers were produced. Their morphologies before and after mechanical tests were analyzed and discussed within the context of their mechanical performance. The mechanical test results were discussed based on used polymer type composition, fiber orientation and composite effect of each layer of bilayer grafts. Produced fibrous xxvii scaffolds were tested with smooth muscle cells to test biocompatibility of presented scaffolds. In conclusion, four articles in the context of this thesis reveal the original and updated sides of the thesis topic. When all studies in the thesis are evaluated as a whole, this thesis has unique contribution to the literature with novel and detailled sub-titles. Furthermore, according to the literature survey, no experimental studies were found available on this topic in Turkey. In this regard, besides being an innovative partner to the international literature with its scientific quality, the outcomes of this thesis are thought to be a guiding light to the national researchers.