<p>Efforts to create a reliable, long–term implantable glucose sensor have been stymied by the effects of the foreign body response and wound healing that introduce delayed response times as well as unpredictable sensor performance. Loss of vascularization from fibrotic encapsulation around implanted sensors is purported as a key contributor to sensor failure, as glucose and oxygen transport to the sensor becomes impeded. Improving sensor performance by increasing angiogenesis and/or reducing capsule thickness using tissue-modifying textured coatings is attractive because texturing is not dependent upon a depletable drug reservoir. A significant range of materials and pore sizes are capable of promoting angiogenesis and reducing capsule thickness, provided pores have open-architecture with dimensions sufficiently large enough to allow inflammatory cell infiltration. </p><p><br></p><p>Poly–L–lactic acid was gas foamed/salt leached with ammonium bicarbonate to produce porous coatings for Medtronic MiniMed SOF–sensor glucose sensors. Coating properties included 30μm pore diameters, 90% porosity, and 50μm wall thickness. Cytotoxicity, degradation, and sensor response time studies were performed to ensure the porous coatings were non–toxic and negligibly retarded glucose diffusion prior to <italic>in vivo</italic> testing. Histology was used to evaluate angiogenesis and collagen deposition adjacent to porous coated and bare (i.e. smooth, uncoated) non–functional sensor strips after three weeks in the rat dorsal subcutis. Functional Medtronic glucose sensors, with and without porous coatings, were percutaneously implanted in the rat dorsum to assess if the angiogenic–inducing properties observed around the non–functional porous coated sensor strips translated into stable, non–attenuated sensor signals over two and three weeks. MiniLink<super>TM </super>transmitters were attached to the rats, permitting continuous glucose monitoring. Vessel counts and collagen deposition adjacent to sensors were determined from histological analysis. A one–sided dorsal window model was developed to further evaluate the interplay between vascularization and sensor performance Sensors were inserted beneath the windows, allowing visualization of microvascular changes adjacent to sensor surfaces, with simultaneous evaluation of how vascular changes impacted interstitial glucose monitoring. </p><p><br></p><p>Porous coating did have angiogenic–inducing effects on the surrounding tissue. When fully implanted in the rat dorsum, sensor strips with porous coatings induced three–fold more vessels within 100μm<super>2</super> of the sensor strip surface after three weeks and two-fold more cumulative vessel lengths within 1mm<super>2</super> after two weeks, compared to bare surfaces. In contrast, when percutaneously implanted in the rat dorsum, porous coated and bare sensors were equally highly vascularized, with two–fold more vessels than fully implanted bare sensors. </p><p><br></p><p>Despite increased angiogenesis adjacent to percutaneous sensors, sensor signal attenuation occurred over 14 days, suggesting that angiogenesis plays a secondary role in maintaining sensor function. Percutaneously implanted porous coated sensors had greater reductions in baseline current (20 to 50+%) over two weeks than bare sensors (10 to 30%). Mechanical stresses imposed by percutaneous tethering may override the beneficial effects of porous coatings. Furthermore, integration of the porous coating with the surrounding tissue may have increased tissue tearing at the porous coating–tissue, increasing inflammation and collagen deposition resulting in greater signal attenuation compared with bare sensors. Future investigations of the role mechanical irritation has on wound healing around percutaneous glucose sensors are warranted.</p> / Dissertation

Made available in DSpace on 2014-12-17T15:01:51Z (GMT). No. of bitstreams: 1 JoseNG_TESE.pdf: 4686361 bytes, checksum: ece8f07ff848703fdc4412907a924e10 (MD5) Previous issue date: 2010-04-08 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / This work aims at studying the influence of the concentration of calcite, its grain size and sintering temperature to obtain porous coating formulations that meet the design specifications. The experiments involved the physical-chemical and mineralogical caracterization of the raw materials, and mechanical tests on specimens dried and sintered, performing a planning mixture and factorial experiment, using the response surface methodology. The ceramic bodies studied were prepared by dry process, characterized, placed in conformity by uniaxial pressing and sintered at temperatures of 940 ? C, 1000?C, 1060?C, 1120?C and 1180?C using a fast-firing cycle. The crystalline phases formed during sintering at temperatures under study, revealed the presence of anorthite and wolastonite, and quartz-phase remaining. These phases were mainly responsible for the physical and mechanical properties of the sintered especimens. The results shown that as increases the participation of carbonate in the composition of ceramic bodies there is an increase of water absorption and a slight reduction in linear shrinkage for all sintering temperatures. As for the mechanical strength it was observed that it tended to decrease for sintering at temperatures between 940 ? C and 1060 ? C and to increase for sintering at temperatures above 1060 ? C occurring with greater intensity for compositions with higher content of calcite. The resistence decreased with increasing participation of quartz in all sintering temperatures. The decrease in grain size of calcite caused a slight increase in water absorption for formulation with the same concentration of carbonate, remaining virtually unchanged the results of linear shrinkage and mechanical strength. In conclusion, porous ceramic coating (BIII) can be obtained using high concentrations of calcite and keeping the properties required in technical standards and that the particle size of calcite can be used as tuning parameter for the properties of ceramic products. / Este trabalho objetiva estudar a influ?ncia da concentra??o de calcita, sua granulometria e temperatura de sinteriza??o na obten??o de formula??es para revestimento poroso que atendam as especifica??es da norma. Os experimentos envolveram a caracteriza??o f?sico qu?mica e mineral?gica das mat?rias-primas, e ensaios mec?nicos nos corpos de prova secos e sinterizados, precedendo-se de um planejamento de experimento de mistura e fatorial, com o uso da metodologia de superf?cie de resposta. As massas cer?micas estudadas foram preparadas pelo processo via seca, caracterizada, conformada por prensagem uniaxial e sinterizadas nas temperaturas de 940?C, 1000?C, 1060?C, 1120?C, e 1180?C utilizando um ciclo de sinteriza??o r?pido. As fases cristalina formadas durante a sinteriza??o nas temperaturas em estudo, revelaram a presen?a de anortita e wolastonita, al?m de quartzo com fase remanescente. Estas fases foram as principais respons?veis pelas propriedades f?sico-mec?nica dos corpos de provas sinterizados. Verificou-se que conforme se aumenta a participa??o do carbonato na composi??o das massas cer?micas ocorre um incremento de absor??o de ?gua e uma pequena redu??o da retra??o linear para todas as temperaturas de sinteriza??o. J? para a resist?ncia mec?nica houve uma tend?ncia de redu??o para sinteriza??o entre 940?C e 1060?C e aumento para sinteriza??o acima da temperatura de 1060?C ocorrendo com maior intensidade para formula??es com maior teor de calcita, e houve diminui??o da resist?ncia com o aumento da participa??o do quartzo em todas as temperaturas de sinteriza??o. A diminui??o da granulometria da calcita provocou um leve aumento na Absor??o de ?gua para formula??o com a mesma concentra??o desse carbonato mantendo praticamente inalterados os resultados de retra??o linear e resist?ncia mec?nica. Conclui-se que produtos cer?micos para revestimento poroso (BIII) podem ser obtidos utilizando altas concentra??es de calcita e mantendo-se as propriedades exigidas em normas t?cnicas e que a granulometria da calcita pode ser usada como par?metro de ajuste para as propriedades dos produtos cer?micos