LEE- Tekstil Mühendisliği-Yüksek Lisans

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    Fabrication and characterization of biodegradable fibrous webs for vascular graft structures
    (Graduate School, 2022-01-10) Öztemur, Janset ; Eniş Yalçın, İpek ; 503181804 ; Textile Engineering ; Tekstil Mühendisliği
    Cardiovascular diseases are among the most common types of non-infectious diseases, causing approximately 20 million deaths worldwide to date. Deaths caused by cardiovascular diseases, triggered by the increase in the stress level brought about by settling from rural to urban at the global level and the spread of unhealthy eating habits, increased by 21.1% between 2007 and 2017. According to the World Health Organization data, it is estimated that the annual incidence of cardiovascular disease-related mortality will increase to 23.6 million worldwide by 2030. On the other hand, while the Covid-19 pandemic, which affected the entire world, caused an unexpected increase in cardiovascular diseases, the fact that people with these types of diseases were among the ones defined as a high-risk group once again revealed the seriousness of the situation. Mild cardiovascular diseases are treated with dietary modification, lifestyle changes, and medications, while treatment options for more damaged blood vessels usually consist of bypassing a part of the autologous vessel to replace the diseased part. The use of autologous vessels requires an additional clinical procedure such as vascular integration to the damaged area, as well as taking veins from certain parts of the body such as leg vein, forearm artery, and thoracic artery for this procedure. In addition to the aforementioned risks, dimensional incompatibilities may also occur in some cases. For this reason, the necessity of finding alternative solutions in order to overcome these problems experienced in autologous vessels is among the prominent issues in recent years. Although allografts taken from donors or cadavers and xenografts procured from animals are alternatives, they cannot fully meet this need due to the lack of donor/incompatibility and their short lifespan. Replacing the damaged vessel with a vascular graft in the treatment of cardiovascular diseases is one of the preferred methods of recent times, but problems such as infection formation, risk of thrombosis, incompatibility in radial elasticity, inadequacy in cell development, especially in small-caliber vessel changes, limit surgical success. At this point, the search for new materials and constructions has come to the fore, and the design of biodegradable scaffolds that can be replaced by an autograft produced by the body over time has taken its place among the priority research topics. Although important findings have been obtained in the research that has accelerated in the last 10 years, there is no small-caliber biodegradable vascular graft that has achieved commercial success yet. In order to meet the need, it is expected from the vascular graft to provide structural support and encourage cellular activity for the body to produce its vessel. The most important step in approximating vascular grafts designs to native blood vessel structure is to optimize the surface morphology and develop a microenvironment in which cells can attach and proliferate. For this reason, the features of the graft surface should be well understood and morphological criteria should be determined. Within this thesis, a detailed literature review is realized to understand the native artery structure and an experimental study is carried in three parts including the selection of biopolymers, optimization of solution and production parameters, and morphological, structural, thermal, and chemical analyses of the structures. The first experimental part of the thesis is a preliminary study that includes the selection of biomaterials as well as optimization of solution parameters (polymer concentration and blend ratio) and production parameters (feed rate, voltage, and tip-collector distance). A literature review is performed for surfaces produced by electrospinning using low molecular weight polycaproclactone (PCL) and polylactic acid (PLA) polymers as part of this investigation. The affects of parameters like molecular weight, concentration, and blending ratio on surface morphology, smooth fiber production, and fiber diameter parameters are examined during the research work. Electrospinning parameters are systematically studied, and the influences of these parameters on fiber production are determined. Basic parameters such as voltage, feed rate, and tip-collector distance have been optimized in this context by considering the environment's temperature and humidity, as well as the characteristics of the polymer solution. In the first stage, PCL at 16, 18, and 20 % concentrations, PLA at 7, 8, and 9% concentrations and 12% concentration of PLA/PCL (25/75 and 50/50 ratios) are used for surface formation. In this context, a definite conclusion is reached about the polymers to be used in the thesis by evaluating the performances of the determined parameters in the fibrous surface formation process and the morphological properties analyzed by scanning electron microscopy (SEM); furthermore, polymer solution concentration ranges and blending ratio are determined. The results indicate that the spinnability of low molecular weight PCL (45,000 Mn) is insufficient since either bead formation or thick and discontinuous fiber-like forms are observed in all polymer concentrations while neat PLA and PLA/PCL blends have better spinnability, which allows smooth fiber production. In the second part of the thesis, higher molecular weight PCL (80,000 Mn) is introduced to the fibrous webs in order to take the advantage of its better mechanical properties and spinnability. Similar to the preliminary part, PCL, PLA and PCL/PLA blends are studied, but polymer concentration ranges are kept constant as 6, 8, and 10% for all polymeric structures. The morphologies of the electrospun webs are observed by SEM, also fiber diameter and porosity values are measured. Thus, the polymer concentration at which smooth and fine fibers are obtained is determined for neat PLA and PCL in addition to PLA/PCL blends. The hydrophobicity of the surfaces is evaluated by water contact angle analysis (WCA). Differential scanning calorimetry (DSC) is used to observe the thermal behavior of the surfaces during heating and cooling to investigate the crystallinity of the surfaces that provide insights about biodegradability processes. Although it is not possible to obtain fibers at low polymer concentrations on all polymeric surfaces, 8%, and 10% polymer concentration allow continuous fiber formation; moreover, an expected relationship between fiber diameter and porosity ratio is detected. Surfaces with the finest fibers are those with the highest porosity. On the other hand, the thermal behavior of the surfaces is in line with the literature and the highest crystallinity is that of PCL with about 40%. In the last and final part of the thesis, poly (L-lactide) (PLLA), a derivative of PLA, is also introduced in the study, and its effects on surface properties are investigated. Within the scope of developing the most suitable surface for vascular grafts, which is one of the major objectives of the study, different blending ratios for both PLA/PCL and PLLA/PCL are determined in detail. Similar to previous experimental parts, the structures are mainly subjected to SEM, Fourier-transform infrared spectroscopy (FTIR), and DSC analyses, and the effects of blend ratios on morphological, thermal, and chemical properties are investigated in details. It has been observed that the fiber diameter increases with the increase of the ratio of PLA, which has a high molecular weight, in the PCL structure, but the increase in the ratio of PLLA, which has a lower molecular weight than PCL, in the PCL structure causes a decrease in fiber diameter. It has been determined that the polymer ratio is very effective on the fiber diameter depending on the molecular weight of the polymers, and during the thermal analysis, it determines the characteristic curves in the heating and cooling processes. Selected samples of PLA100, PCL100, PLA20PCL80, PLA50PCL50, PLLA20PCL80, and PLLA50PCL50 are subjected to biodegradability analysis at 1st, 3rd, and 5th months. All samples except PLA20PCL80 showed an increase in degradation rate in consecutive months. It is thought that this exception ocuurs in the PLA20PCL80 because of the measurement accuracy. As expected and as seen in the literature research, the degradation rate of PLA (14.29% and 40%, respectively) at the end of the 3rd and 5th months is considerably higher than that of PCL (2.17% and 3.70%, respectively). On the other hand, it is observed that 50% PLA ratio in the blend considerably increases the weight loss of the surface. Moreover, the addition of PLLA on surfaces is also found to accelerate biodegradation, similar to PLA. Cell analysis (MTS) consists of the proliferation of fibroblast and human umbilical vessel endothelial cells (HUVECs), which are one of the basic cells of the native vascular structure. In the content of MTS cellular analysis, affirmative outcomes are obtained in both fibroblast cells and HUVECs compared to control samples, and it is observed that each surface is a suitable environment for cells to live. Besides, PLA appears to have a positive effect on cell viability on PCL up to 20%, and the highest cell proliferation occurred in the PLA20PCL80 sample. The findings of the experimental studies as detailed in the three stages above shed light on the best way to examine the morphological, chemical, thermal, and biological properties of a wide variety of surfaces produced from PLA, PLLA, and PCL polymers. Surfaces designed and fabricated according to the optimized parameters are promising for layered vascular graft structures. In the studies that will take place in the thesis' continuation, small-caliber vessel grafts will be designed and fabricated from these optimized surfaces with desired orientation levels, taking into account the mechanical properties of the vessels and advanced cell activities both in-vitro and in-vivo.