Yes / Highly-oriented poly(l-lactic acid) (PLLA) with fibrillar structure and micro-grooves was fabricated through solid hot drawing technology for further improving the mechanical properties and blood biocompatibility of PLLA as blood-contacting medical devices. In order to enhance the melt strength and thus obtain high orientation degree, PLLA was first chain extended with ethylene glycol diglycidyl ether (EGDE). The extending degree as high as 25.79 mol% can be obtained at 0.7 wt% EGDE content. The complex viscosity, storage and viscous modulus for chain extended PLLA were improved resulting from the enhancement of molecular entanglement, and consequently higher draw ratio can be achieved during the subsequent hot stretching. The tensile strength and modulus of PLLA were improved dramatically by stretching. The stress-induced crystallization of PLLA occurred during drawing. The interfacial tension (γs·blood) between PLLA surface and blood decreased by chain extension and molecular orientation, indicating the weakened interaction between bioactive substance in the blood and the surface of PLLA. Modification and orientation could significantly enhance the blood compatibility of PLLA by prolonging clotting time and decreasing hemolysis ratio, protein adsorption and platelet activation. The bionic character of oriented PLLA and its anti-coagulation mechanism were tried to be explored. / This research was supported by National Natural Science Foundation of China (Grant No. 51303109)

This research studied Ho166/PLLA microspheres, a promising treatment for tumours in the liver. The Ho166 is generated through a neutron capture reaction during irradiation in a nuclear reactor. Previous work has found that neutron-irradiation in-core causes damage to microspheres and causes additional degradation to progress once suspended in media. The cause of this damage was not well understood and is the focus of this research. This research studied factors present in-core such as heat, gamma radiation, and impacts of lead shielding, for their impact on microsphere quality. Additionally, this research looked at the potential of reactive oxygen species causing damage once microspheres are suspended in liquid. Thresholds for damage were identified to correlate with the glass transition temperature of poly- l-lactic acid. Exposure to gamma radiation induces heating, as well as structural changes to the polymer which shifts the temperature where the glass transition occurs. Damage formed from gamma radiation, independent of other variables, was seen at extreme accumulated doses. Notably, exposure to gamma radiation and heat did not cause a progression of damage over time. Samples exposed only to these factors remained stable in solution for extended periods. A theory was proposed that reactive oxygen species formed by the interaction of ionizing radiation with the suspending media may be causing the progression of damage over time. This factor would only be present for microspheres having undergone neutron capture reactions, forming radioactive holmium. Testing confirmed a potential impact of radiation interactions with the suspending media contributing to damage progression. Several thicknesses of lead shielding surrounding the sample chamber were tested in-core. There were significant impacts on temperature, neutron flux, and microsphere quality. / Thesis / Master of Science (MSc) / This research studied Ho166/PLLA microspheres, a promising treatment for tumours in the liver. The preparation of this treatment includes microspheres being neutron irradiated in the core of a nuclear reactor. Irradiation in-core leads to damage of microspheres. This research studied factors present in-core such as heat, gamma radiation, and thickness of lead shielding, for their impact on microsphere quality. Additionally, this research looked at the potential of reactive oxygen species causing damage once microspheres are suspended in liquid. Thresholds for damage were identified for temperature and gamma radiation exposure. Radiation interactions in liquid suggest possible damaging effects over time. Finally changing the thickness of lead shielding in core had significant impact on temperature, neutron flux, and microsphere quality.

No description available.

In the field of maxillofacial surgery, the treatment for the recovery of the fracture at condyle region of the mandible has been carried out using Bio-metals such as Titanium, Cobalt, Stainless-Steel because they were considered the standard materials for Implant plate devices for fracture fixation. Using these materials have led to undesired disturbances where the patient must undergo secondary surgery after recovery leading to exposure of the fracture site to the surrounding, metal-ion release into the human system, stress-shielding and interruption during imaging i.e. (Computerized tomography scans). The healing of the mandible requires a delicate and stable fixation procedure for the bone structure to heal. Bio-resorbable materials are the renovation for substituting metals for recovery of the fracture. The main dis-advantage using resorbable plates is absence of mechanical strength and stability. Bio-composites are the innovation for the treatment of the fractures the main study for this thesis is comparing the combination bio-ceramic and bio-resorbable materials using Finite Element Analysis software.

Meniscus is a fibrocartilaginous tissue which plays an important role in joint stability, lubrication, and load bearing and transmission. Meniscal tears are commonly encountered in sports activities, or caused by degeneration of the cartilage with ageing. They lead to pain, loss of work, disturbed biomechanics of the knee and inability to walk or even move the legs. As the meniscal tissue is avascular in the inner portion, injury to this part does not heal by itself, and therefore treatments are needed. In some cases when complex tears occur, the tissue cannot be successfully treated with the conventional methods. Tissue engineering appears to be a promising alternative to treat such complex tears. It includes the application of cells on scaffolds (or cell carriers), and provision of bioactive agents to the site of injury in order to regenerate the damaged tissue. The cells and the bioactive agents are involved in the synthesis of the new tissue, while the scaffold acts as a support to guide the cells until the new tissue is formed, and it is slowly absorbed by the body leaving the new tissue behind. Thus, a natural tissue is generated at the end. Few studies have been reported on the tissue engineering of meniscus, but neither of them was able to completely mimic the meniscus structure, nor could they succeed in constructing scaffolds with sufficiently high tensile properties. In the current in vitro study, a novel 3D construct was proposed, in which the natural tissue is perfectly mimicked. The 3D construct consisted of aligned collagen fibers embedded within a foam network which stabilizes the structure. The foam was prepared by freezing a polymer solution with a certain concentration, and lyophilizing it. Aligned fibers were aimed to improve the tensile properties. The construct was impregnated in alginate gel, which was then crosslinked, to improve the compressive properties. The foam was prepared from (poly(L-lactic acid)/poly(lactic-co-glycolic acid) (PLLA/PLGA) solutions of various concentrations (2%, 2.5%, 3%, and 4% w/v) and at different freezing temperatures (-20oC or -80oC) to select the best preparation condition. After analysis of the microstructure and mechanical properties, foams prepared from 3% polymer solution frozen at -20oC were found to be the most appropriate for use as scaffold for the 3D construct, since they had large pores, high and interconnected porosity, as well as high mechanical strength. The 3D constructs were seeded with human meniscus cells and incubated for 21 days. Cell behavior on the constructs was examined. Cell attachment and proliferation was found to be better with the constructs not coated with alginate. However, the constructs coated with alginate demonstrated higher compressive strength. It was also found that incorporation of collagen fibers significantly improved the tensile properties. All the constructs were shown to lead to the production of extracellular components specific for fibrocartilages, and thus it was concluded that they were promising for use in meniscal replacement.

Controlling the surface morphology and degree of crystallinity of poly(L-lactic acid) (PLLA) substrates have recently attracted considerable attention because of their applications in cell adhesion, tissue engineering, and drug delivery. Several techniques have been used to fabricate PLLA substrates, some of which may be invalid because PLLA can degrade during fabrication processes. This dissertation provides the Langmuir-Blodgett (LB) technique as a mechanism for fabricating PLLA substrates at temperatures where PLLA degradation is uncommon. In order to fully understand surface morphologies of PLLA LB-films, studies of Langmuir monolayers at the air/water (A/W) interface using surface pressure-area (Pi-A) isotherm and Brewster angle microscopy (BAM) are vital. PLLA exhibits a first-order liquid expanded to condensed (LE/LC) phase transition with molar mass dependent critical phenomena, the first such observation for a homopolymer Langmuir monolayer. Atomic force microscopy (AFM) images of PLLA LB-films prepared in the LC phase exhibit well-ordered lamellar structures. Molar mass scaling of lamellar dimensions, x-ray reflectivity, and reflection absorption infrared spectroscopy (RAIRS) measurements on PLLA LB-films are consistent with PLLA existing as single molecule 10/3-helices at the A/W interface. Morphologies observed after collapse of the LC monolayer are dependent upon the collapse mechanism and subsequent thermal treatment. For temperatures below the LE/LC critical temperature (Tc), two mechanisms are identified for the formation of three dimensional structures: a buckling and stacking of lamellar monolayers on top of existing lamellae during constant compression rate experiments, and a modified nucleation and growth mechanism during isobaric area relaxation experiments. PLLA LB-films prepared in different Langmuir film phases at temperatures below Tc all contain lamellae with different surface roughnesses and similar helical content. Conventional thermal annealing studies on PLLA LB-films reveal that well-ordered lamellar features are destroyed after annealing the LB-films at bulk crystallization temperature through a melting-recrystallization process, which is confirmed by RAIRS and AFM. Our results may prove useful for studying critical behavior and experimentally testing scaling predictions for two dimensions, the development and testing of theories for crystallization in confined geometries, and separating the roles that roughness and crystallinity play in cell adhesion and spreading on biocompatible polymer surfaces. / Ph. D.

This research is the first systematic investigation of solid-state orientation as a novel method for controlling drug release from biodegradable polymers. The effect of various degrees of polymer orientation was studied in oriented Poly (L-lactic acid) (PLA) films containing curcumin and theophylline as model drugs. Additionally, direction specific drug release was studied from oriented PLA rods containing paracetamol. The films oriented to 2X uniaxial constant width (UCW) or 2X2Y biaxial draw ratio showed retardation of drug release, when their nematic structure was stabilised by the presence of crystalline theophylline. Contrarily, the same films when contained solid solution of curcumin, shrunk in the release medium and exhibited a release profile similar to the un-oriented films. All films oriented to the UCW draw ratio ≥ 3X contained α crystalline form of PLA and showed acceleration of drug release proportionate to the draw ratio. According to the proposed mechanism augmented formation of water filled channels in these films was responsible for faster drug release. Similarly, the paracetamol loaded PLA rods die-drawn to uniaxial draw ratios ≥ 3X exhibited enhancement of drug release. Importantly, the amount of drug released along the oriented chain axis was significantly larger than that in the perpendicular direction. Drug release from the die-drawn rods was accelerated by a greater degree than that observed from the oriented films. This can be correlated to the differences in their size, geometry and the crystalline form of PLA. In conclusion, the current study provided substantial evidence that solid-state orientation can offer a control over drug release from PLA.

Orientador: Eliana Aparecida de Resende Duek / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecanica / Made available in DSpace on 2018-08-10T00:47:14Z (GMT). No. of bitstreams: 1 Moura_LucasAlves_M.pdf: 3634046 bytes, checksum: 536a898e97f786f07e4ccf738d9d67e5 (MD5) Previous issue date: 2007 / Resumo: A regeneração tecidual guiada (RTG) é uma técnica utilizada na Periodontia para permitir a neoformação de um novo aparato de inserção periodontal do dente (osso alveolar, ligamento periodontal e cemento). Na Periodontia, a utilização de polímeros biorreabsorvíveis vem ganhando confiabilidade e importância devido a não necessidade de uma segunda intervenção cirúrgica para remover a membrana, porém poucas membranas atendem a todos os critérios da RTG, que são biocompatibilidade, exclusão celular, manutenção do espaço a ser regenerado, integração à atividade tecidual, facilidade de utilização e atividade biológica. Um polímero biorreabsorvível muito estudado é o poli (L-ácido láctico) (PLLA), porém ele é polímero semicristalino muito rígido e com longo período de degradação, contudo ao se adicionar em sua composição um plastificante, o tri-etil-citrato, a membrana resultante seria mais flexível, microporosa e teria seu tempo de degradação reduzido. Esta pesquisa avaliou, através de estudo in vivo, a resposta inflamatória e a manutenção de um espaço vital para a regeneração óssea sob membranas de PLLA/tri-etil-citrato, em três diferentes proporções polímero/plastificante, implantadas na calota craniana de coelhos, analisando, assim, a capacidade destas membranas em se adaptar aos critérios da RTG periodontal. Paralelamente ao estudo in vivo, foram realizados estudos da degradação in vitro, com ensaios mecânicos de tração, de microscopia eletrônica de varredura e de calorimetria diferencial de varredura (DSC). Notou-se que as membranas de concentração PLLA/tri-etil-citrato de 85/15 apresentaram características mais adequadas para a RTG periodontal tanto no estudo in vivo quanto no in vitro / Abstract: Guided tissue regeneration (GTR) is a technique used in the periodontal practice to allow the neoformation of a new apparatus of teeth periodontal attachment (alveolar bone, periodontal ligament and cementum). In Periodontology, the use of bioresorbable polymers is gaining trustworthiness and importance due the non required second surgical intervention to remove the membrane, however few membranes fit in all GTR criteria, which are biocompatibility, cellular exclusion, space maintainer, integration to tissue activity, easy usage and biological activity. A bioresorbable polymer very studied is poly(L-lactic acid) (PLLA), however it is a very rigid semicrystalline polymer and with a long degradation period, but by adding in its composition a plasticizer, the tri-ethyl-citrate, the resultant membrane would be more flexible, microporous and would have its degradation time reduced. This research evaluated, through in vivo study, the inflammatory response and the maintenance of a vital space for bone regeneration under PLLA/tri-ethyl-citrate membranes, in three different polymer/plasticizer proportions, implanted in rabbits calvarial bone, analyzing, thus, the capacity of these membranes in adapting to the criteria of periodontal GTR. Simultaneously to this study, it had been carried out studies of in vitro degradation, with mechanical testing, scanning electronic microscopy and differential scanning calorimetry (DSC). It was observed, that the highest concentration membranes PLLA/tri-ethyl-citrate (85/15) showed themselves more adequate characteristics for the periodontal GTR on in vivo study as well on in vitro / Mestrado / Materiais e Processos de Fabricação / Mestre em Engenharia Mecânica

This research is the first systematic investigation of solid-state orientation as a novel method for controlling drug release from biodegradable polymers. The effect of various degrees of polymer orientation was studied in oriented Poly (L-lactic acid) (PLA) films containing curcumin and theophylline as model drugs. Additionally, direction specific drug release was studied from oriented PLA rods containing paracetamol. The films oriented to 2X uniaxial constant width (UCW) or 2X2Y biaxial draw ratio showed retardation of drug release, when their nematic structure was stabilised by the presence of crystalline theophylline. Contrarily, the same films when contained solid solution of curcumin, shrunk in the release medium and exhibited a release profile similar to the un-oriented films. All films oriented to the UCW draw ratio ≥ 3X contained α crystalline form of PLA and showed acceleration of drug release proportionate to the draw ratio. According to the proposed mechanism augmented formation of water filled channels in these films was responsible for faster drug release. Similarly, the paracetamol loaded PLA rods die-drawn to uniaxial draw ratios ≥ 3X exhibited enhancement of drug release. Importantly, the amount of drug released along the oriented chain axis was significantly larger than that in the perpendicular direction. Drug release from the die-drawn rods was accelerated by a greater degree than that observed from the oriented films. This can be correlated to the differences in their size, geometry and the crystalline form of PLA. In conclusion, the current study provided substantial evidence that solid-state orientation can offer a control over drug release from PLA.

No description available.