<p>As an increasingly prevalent chronic disease, diabetes represents one of the fastest growing health burdens to both the developed and developing world. In an effort to improve the management and treatment of diabetes, implantable sensors that continuously monitor glucose levels have become popular alternatives to patient-administered finger prick measurements of blood glucose. However, following implantation, the performance of these implants suffers from inaccurate and erratic readings that compromise their useful lives. As a result, implantable glucose sensors remain limited as a platform for the reliable management of diabetes. While the interaction between the sensor and its surrounding tissue has been posited as a culprit for erroneous in vivo sensor performance, there remains little evidence to support that theory.</p><p>This dissertation describes the effects that implant-associated tissue reactions have on implantable sensor function. Since tissue response to an implant changes over time, the overall effect of these tissue reactions is broken into two temporal phases: (1) the phase of weeks to months following implantation when a mature foreign body capsule is present around the sensor and (2) the phase of days to weeks immediately following sensor implantation when a provisional matrix of proteins and inflammatory cells envelops the sensor.</p><p>Late stage sensor responses to implantation are marked by both an attenuated sensor signal and a significant time lag relative to blood glucose readings. For this later stage of sensor response, a computational model of glucose transport through the interstitial space and foreign body capsule was derived and implemented. Utilizing physiologically relevant parameters, the model was used to mechanistically study how each constituent part of the capsular tissue could affect sensor response with respect to signal attenuation and lag. Each parameter was then analyzed using logarithmic sensitivity analysis to study the effects of different transport variables on both lag and attenuation. Results identified capsule thickness as the strongest determinant of sensor time lag, while subcutaneous vessel density and capsule porosity had the largest effects on attenuation of the sensor signal.</p><p>For the phase of early stage tissue response, human whole blood was used as a simple ex vivo experimental system. The impacts of protein accumulation at the sensor surface (biofouling effects) and cellular consumption of glucose in both the biofouling layer and in the bulk (metabolic effects) on sensor response were assessed. Medtronic Minimed SofSensor glucose sensors were incubated in whole blood, plasma diluted whole blood, and cell-free platelet poor plasma (PPP) to analyze the effects of different blood constituents on sensor function. Experimental conditions were then simulated using MATLAB to predict the relative impacts of biofouling and metabolic effects on the observed sensor responses. It was found that the physical barrier to glucose transport presented by protein biofouling did not hinder glucose movement to the sensor surface. Instead, glucose consumption by inflammatory cells was identified as the major culprit for generating poor sensor performance immediately following implantation.</p><p>Lastly, a novel, biomimetic construct was designed to mimic the in vivo 3D cellular setting around the sensor for the focused in vitro investigation of early stage effects of implantation on glucose sensor performance. Results with this construct demonstrate similar trends in sensor signal decline to the ex vivo cases described above, suggesting this construct could be used as an in vitro platform for assessing implantable glucose sensor performance.</p><p>In total, it may be concluded from this dissertation that instead of sensors "failing" in vivo, as is often reported, that different physiological factors mediate long term sensor function by altering the environment around the implant. For times immediately following implantation, sensor signals are mediated by the presence of inflammatory macrophages adhered on the surface. However, at longer times post-implantation, sensor signals are mediated not by the consumptive capacity of macrophages, but instead by the subcutaneous vessel density surrounding the sensor as well as the porosity and thickness of the foreign body capsule itself. Taken in concert, the results of this dissertation provide a temporal framework for outlining the effects of tissue response on sensor performance, hopefully informing more biocompatible glucose sensor designs in the future.</p> / Dissertation

Fibroin is a biopolymer obtained from the cocoons of the Bombyx mori silkworm that offers many unique advantages. In this thesis work, fibroin was processed into a regenerated film and examined for potential biomaterial applications. The adsorption of bovine serum albumin onto the fibroin film was investigated to examine the biocompatibility of the film, and it was found that BSA adsorption capacity increased with an increase in BSA concentration. At 10 mg/mL of BSA, the BSA sorption reached 0.045 mg/cm2. This level of BSA is indicative of good blood compatibility and biocompatibility of the fibroin. The gas permeabilities of oxygen, nitrogen, and carbon dioxide were tested for potential applications in contact lenses and wound dressings. Over a pressure range of 70 – 350 psig, the permeability of oxygen and nitrogen was 5 Barrer, while that of carbon dioxide ranged from 26 to 37 Barrer. The oxygen transmissibility of the fibroin films prepared in this study was on the low end required for use in daily wear contact lenses, but sufficient to aid the healing process for use in wound dressings. The permeability and diffusivity of four model drugs in the fibroin film was investigated for potential applications in controlled drug release. The permeability at higher source concentrations leveled out to 0.8 – 4.3 x 10-7 cm2/s depending on the drug tested. The diffusion coefficient determined from sorption experiments was approximately 1.8 x 10-9 cm2/s, while the diffusion coefficients from desorption experiments were determined to be 0.8 – 2.7 x 10-9 cm2/s. The magnitude of the drug permeability and diffusivity are consistent with many other controlled release materials, and the fibroin film showed good potential for use in controlled release.

Thesis (M.S.)--University of Missouri-Columbia, 2008. / "May 2008" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Includes bibliographical references.

Thesis (M.S.)--University of Michigan, 1979.

Thesis (M.S.)--Mississippi State University. Department of Agricultural and Biological Engineering. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--Mississippi State University. Department of Agricultural and Biological Engineering. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--University of Michigan, 1979.

Thesis (M.S.)--Duquesne University, 2007. / Title from document title page. Abstract included in electronic submission form. Includes bibliographical references (p. 48-51) and index.

Submitted by PAULA MASETTI null (paulamasetti@foar.unesp.br) on 2016-05-19T20:53:43Z No. of bitstreams: 1 Tese Corrigida Paula.pdf: 1034060 bytes, checksum: f68e39b40f15f384b00f2c850a864a26 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-05-23T18:59:36Z (GMT) No. of bitstreams: 1 masetti_p_me_arafo.pdf: 1034060 bytes, checksum: f68e39b40f15f384b00f2c850a864a26 (MD5) / Made available in DSpace on 2016-05-23T18:59:36Z (GMT). No. of bitstreams: 1 masetti_p_me_arafo.pdf: 1034060 bytes, checksum: f68e39b40f15f384b00f2c850a864a26 (MD5) Previous issue date: 2016-04-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo deste estudo foi avaliar o efeito cumulativo das soluções desinfetantes na citotoxicidade de resinas acrílicas para base (Vipi Wave) e reembasamento (Tokuyama Rebase II) de próteses. Corpos de prova com 14 mm de diâmetro e 1,2 mm de espessura foram distribuídos em grupos (n=3) de acordo com o tipo de solução: água destilada, digluconato de clorexidina a 2%, perborato de sódio a 3,8%, hipoclorito de sódio a 0,5% e vinagre de maçã, e de acordo com o tempo de imersão: 0, 1, 3 e 6 meses. Os corpos de prova, tanto de base quanto de reembasamento, ficaram 8 horas imersos nas soluções e 16 horas em água destilada, simulando desinfecção noturna das próteses. As soluções foram trocadas diariamente. Após os diferentes períodos de imersão, as amostras foram colocadas em meio de cultura por 24 horas para obtenção de extratos para análise da citotoxicidade sobre queratinócitos humanos (HaCaT: 0341). O metabolismo celular foi avaliado pelo teste Alamar Blue ®. Empregou-se análise de variância (ANOVA) e teste de Tukey, com significância de 5%. Os resultados demonstraram que o tipo de resina não teve influência sobre o metabolismo celular. Além disso, a imersão das amostras de resina acrílica para base e reembasamento de próteses em água destilada, perborato de sódio a 3,8% e hipoclorito de sódio a 0,5% não influenciou o metabolismo celular dos queratinócitos, independentemente do tempo de imersão. Os extratos obtidos a partir da imersão das amostras em digluconato de clorexidina a 2% ou em vinagre de maçã durante 3 e 6 meses foram considerados intensamente citotóxicos. Pôde-se concluir que o digluconato de clorexidina a 2% e o vinagre de maça aumentaram citotoxicidade de resinas acrílicas para base e reembasamento de próteses. / The objective of this study was to evaluate the cumulative effect of disinfectant solutions in cytotoxicity base acrylic resins (Vipi Wave) and reline (Tokuyama Rebase II) of dentures. Samples of 14 mm diameter and 1.2 mm thick were distributed in groups (n = 3) according to the type of disinfectant solution: distilled water, 2% chlorhexidine digluconate, 3.8 % sodium perborate, 0.5% sodium hypochlorite and apple vinegar and in accordance with the immersion time: 0, 1, 3 and 6 months. The samples of both base and of reline, eight hours were immersed in solutions and 16 hours in distilled water, simulating night disinfection of prostheses. The solutions were changed daily. After different periods of immersion, the samples were placed in culture medium for 24 hours to obtain extracts for analysis of cytotoxicity on human keratinocyte (HaCaT: 0341). The cellular metabolism was assessed by Alamar Blue ® test. It used analysis of variance (ANOVA) and Tukey test, with 5% significance. The results demonstrated that the resin type had no influence on cellular metabolism. Furthermore, the immersion of the samples in acrylic resin base and reline dentures in distilled water, 3.8% sodium perborate and 0.5% sodium hypochlorite did not influence the cellular metabolism of keratinocytes, regardless of the time of immersion. The extracts obtained from immersing the samples 2% chlorhexidine digluconate or apple vinegar for 3 and 6 months were considered strongly cytotoxic. It was concluded that chlorhexidine digluconate 2% and apple vinegar increased cytotoxicity of denture base and reline acrylic resins.

Submitted by Aline Cardoso Pereira (aline.cardosopereira@hotmail.com) on 2018-08-02T22:27:37Z No. of bitstreams: 1 DISSERTAÇÃO DE MESTRADO - ALINE C. PEREIRA.pdf: 2161021 bytes, checksum: 07880c29666b475277e0461208a4bf5a (MD5) / Approved for entry into archive by Isabel Pereira de Matos (isabel@fmva.unesp.br) on 2018-08-03T18:51:33Z (GMT) No. of bitstreams: 1 pereira_ac_me_araca_int.pdf: 2161021 bytes, checksum: 07880c29666b475277e0461208a4bf5a (MD5) / Made available in DSpace on 2018-08-03T18:51:33Z (GMT). No. of bitstreams: 1 pereira_ac_me_araca_int.pdf: 2161021 bytes, checksum: 07880c29666b475277e0461208a4bf5a (MD5) Previous issue date: 2018-06-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / As ceratites ulcerativas são comuns na rotina do médico veterinário de pequenos animais, visto que a córnea é uma estrutura vulnerável devido sua exposição ao meio externo. Por compreender uma das estruturas responsáveis pela refração luminosa e participante do mecanismo de formação da imagem, é de extrema importância a integridade da anatomia e transparência da córnea para esta continuar desempenhando suas funções. Estudos ainda são realizados com o intuito de viabilizar opções terapêuticas cirúrgicas para o tratamento de úlceras de córnea complicadas, tentando alcançar uma cicatrização com um menor dano à estrutura corneal e menor opacidade cicatricial, devolvendo a transparência da córnea. Visto que os polímeros biodegradáveis tem se mostrado alvo de pesquisas atuais para aplicações médicas, com este estudo objetivou-se avaliar originalmente a biocompatibilidade da membrana do polímero poli(butileno adipato-co-tereftalato) (PBAT) na córnea e posterior aplicação clínica deste material nas ceratites ulcerativas profundas. Para tal, foi realizada avaliação clínica experimental e histopatológica após enxertia interlamelar do PBAT em córnea de coelhos, ao longo de 60 dias, e acompanhamento da evolução clínica do emprego da membrana de PBAT no tratamento de ceratites ulcerativas complicadas em cães, comparando ao uso do enxerto conjuntival, ao longo de 90 dias. Devido aos baixos sinais de inflamação corneal clínicos e histopatológicos nos coelhos e a cicatrização corneal em todos os cães, sem ocorrência de déficit visual, com o presente estudo acreditamos ter viabilizado mais uma opção terapêutica para as ceratites ulcerativas na medicina veterinária. / Ulcerative keratitis are common in the routine of a small animals veterinary doctor, given that the cornea is a vulnerable structure due to its exposure to external environment. For containing one of the structures responsible for light refraction and participant in the mechanism of formation of images, it is of extreme importance the integrity and transparency of the cornea in order for it to continue to develop its functions. Studies are still performed with the intent of making feasible surgical therapeutic options for the treatment of complicated corneal ulcers, trying to reach cicatrization with less damage to the corneal structure and less scar opacity, seeking corneal transparency. Given that biodegradable polymers have been target of current research for medical applications, the objective of this study was to evaluate originally the biocompatibility of the poly (butylene adipate-co-terephthalate) polymer (PBAT) in the cornea and posterior clinical application of this material in deep ulcerative keratitis. It was performed clinical and histopathological evaluation after interlamellar grafting of PBAT in the cornea of rabbits, over 60 days, and follow-up of the clinical evolution of PBAT membrane in the treatment of complicated ulcerative keratitis in dogs, comparing to the use of conjunctival graft, over 90 days. Due to low levels of clinical and histopathological corneal inflammation found in rabbits and corneal cicatrization in all dogs, without occurence of visual deficit, with this study we believe it was made feasible another therapeutic option for ulcerative keratitis in veterinary medicine.