Submitted by Pedro Silva Filho (pfsilva@ipen.br) on 2017-11-23T12:28:11Z No. of bitstreams: 0 / Made available in DSpace on 2017-11-23T12:28:12Z (GMT). No. of bitstreams: 0 / A Organização Mundial da Saúde (OMS) relata o câncer como uma das principais causas de morte no mundo. O câncer de próstata é o segundo tipo de câncer mais prevalente em homens, com cerca de 1,1 milhão de casos diagnosticados em 2012. Braquiterapia com iodo-125 é uma método de radioterapia que consiste na introdução de sementes com material radioativo no interior do órgão a ser tratado. As sementes de iodo-125 podem ser inseridas soltas ou em cordas poliméricas bioabsorvíveis, mais comumente o poli(ácido lático-co-ácido glicólico) (PLGA). A função do polímero é reduzir a possibilidade de migração das sementes, o que poderia ser prejudicial para órgãos e tecidos saudáveis. De modo a reduzir os custos do tratamento, a síntese dos dímeros L-lactídeo e glicolídeo, para posterior utilização para preparação do PLGA, por meio da polimerização por abertura de anel, é proposta neste trabalho. Adicionalmente, propõe-se a utilização do amino-alcóxido tris(fenolato) de zircônio (IV) como alternativa ao usual octanoato de estanho (SnOct2), uma vez que a toxicidade do estanho permanece como obstáculo na produção do PLGA para aplicações biomédicas. Embora o iniciador de zircônio seja mais lento do que o SnOct2, massas molares relativamente elevadas foram obtidas quando razões monômero/iniciador (M/I) de 1000/1 (24 h), e 5000/1 (48 h) foram utilizadas. Considerando que as unidades glicolila (GA) são mais reativas do que as unidades lactila (LA), tempos longos de reação são necessários para atingir uma razão LA/GA próxima do objetivo do trabalho (85/15). O grau de racemização também depende do iniciador utilizado. As reações de polimerização realizadas com o iniciador de zircônio mostraram um maior grau de racemização, quando comparadas com aquelas realizadas com o SnOct2. Também foi observado um ligeiro aumento na racemização com o tempo. Considerando os resultados obtidos na síntese e purificação dos dímeros, e na síntese do PLGA em condições semelhantes às industriais, foi possível preparar o polímero de alta massa molar com um custo dezenas de vezes inferior ao custo do PLGA no mercado internacional. Os efeitos da radiação gama no PLGA também foram estudados. Doses normalmente aplicadas para esterilizar materiais para aplicações biomédicas foram empregadas: 10, 18, 25 e 50 kGy. A massa molar de todas as amostras irradiadas diminuiu de uma forma proporcional à dose até 56% de perda para 10 kGy e 72% para 50 kGy porém, são menos pronunciadas para doses mais elevadas. Alterações nas propriedades térmicas, tais como temperatura de fusão, temperatura de transição vítrea e a entalpia de cristalização e fusão foram também observadas após a irradiação. / Tese (Doutorado em Tecnologia Nuclear) / IPEN/T / Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP

Annually, about 80,000 people die in the United Kingdom due to myocardial infarction, congestive heart failure, stroke, or from other diseases related to blood vessels. The current gold standard treatment for replacing the damaged blood vessel is by autograft procedure, during which the internal mammary artery (IMA) graft or saphenous vein graft (SVG) are usually employed. However, some limitations are associated with this type of treatment, such as lack of donor site and post-surgery problems that could negatively affect the patient’s health. Therefore, this present work aims to fabricate a synthetic blood vessel that mimics the natural arteries and to be used as an alternative method for blood vessel replacement. Polymeric materials intended to be used for this purpose must possess several characteristics including: (1) Polymers must be biocompatible; (2) Biodegradable with adequate degradation rate; (3) Must maintain its structural integrity throughout intended use; (4) Must have ideal mechanical properties; and (5) Must encourage and enhance the proliferation of the cells. The feasibility of using synthetic biodegradable polymers such as poly (ε- caprolactone) (PCL) and poly (lactide-co-glycolic acid) (PLGA) for fabricating tubular vascular grafts was extensively investigated in this work. Many fundamental experiments were performed to develop porous tissue- engineered polymeric membranes for vascular graft purposes through electrospinning technique to achieve the main aim. Electrospinning was selected since the scaffolds produced by this method usually resemble structural morphology similar to the extracellular matrix (ECM). Hence, four 6mm in diameter tubular shape vascular grafts PCL only, PLGA only, coaxial (core-PCL and shell-PLGA), and bilayer (inner layer-PCL and outer layer-PLGA) was designed and fabricated successfully. The structure and properties of each scaffold membrane were observed by scanning electron microscopy (SEM), and these scaffolds were fully characterized by Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), water contact angle measurements, mechanical tensile test, as well as cell culture studies were carried out by seeding human umbilical vein cells (HUVEC) and human vascular Fibroblast cells (HVF). Moreover, all polymeric grafts underwent degradation process, and the change in their morphological structure properties was studied over 12 weeks at room temperature. All scaffolds were also exposed to a controlled temperature of 37°C for four weeks, in phosphate-buffered saline solution (pH, 7.3). It was found that all scaffolds displayed exceptional fibre structure and excellent degradability with adequate steady weight-loss confirming the suitability of the fabricated scaffolds for tissue engineering applications. The coaxial and bilayer scaffolds degraded at a much slower (and steadier) rate than the singular PCL and PLGA tubular scaffolds. Coaxial grafts fabricated via coaxial needle showed an increase in their fibre diameter and pore size volume than other membranes, but also showed to have significant tensile strength, elongation at fracture, and Young’s modulus. To conclude, all scaffolds have demonstrated to be reliable to adhere and proliferate HUVEC, and HVF cells, but these cells were attracted to the PLGA membrane more than other fabricated membranes.

Despite the recent development in PLA and PLGA based medical devices, there are still needs to further improve the mechanical performance of bioresorbable medical implants and their bioactivity. This is normally done by optimizing the filler compositions in selected groups ofbiodegradable polymer matrices. In this study, the effects of various filler levels on mechanical strength and thermal properties of PLA and PLGA composites were investigated. Composites containing different dosage of osteoconductive HAp with various particles size (0-5μm, 0-50 μm, nano size), β-TCP, bioactive glass and biodegradable Poly-L-lactide and Polylactide-glycolic acid was manufactured with melt blending, using a twin-screw extruder.The samples were investigated by Differential Scanning Calorimetry (DSC), thermo gravimetric analysis (TGA), Scanning Electron Microscopy (SEM), viscometer, three points bending machine, and Optical Microscopy (OM). The Extruder produced a porous profile. The result from TGA and SEM indicated that there was homogenous filler dispersion in the matrix after compounding.The result from DSC and Viscometer shows that there was some degradation duringcompounding. Mechanical properties of composites were modified by adding filler to matrix. The addition of Bioactive glass, as a filler, increases the degradation of the polymer matrix. The best filler that was applied is 0-5μm and nano HAp. Also in in-vitro degradation part of this thesis work, the effects of calcium phosphate materialsare investigated on degradation process.