No description available.

The conception of electrospinning can trace its roots back more than 400 years, when it was observed that rubbed amber can deform a droplet of water on a smooth surface, and is based upon simple concepts of charge separation and surface tension. Since that time, considerable effort has been directed at both the cause and utility of this phenomenon. The specific aim of this dissertation project was to develop an automated electrostatic processing apparatus that was capable of controlling the three-dimensional architecture of an electrospun scaffold to further improve its utility in tissue engineering. The efficacy of using this technique has been well documented and can be adapted to produce tissue engineering scaffolds for a variety of tissues and organs. This apparatus incorporates precise mandrel motion. The system is capable of 0 - 5000 revolution per minute rotation, 0 - 25 inch per second translation and ± 40° rotation about the electrospinning jet axis for repeatable scaffold production. Fiber alignment and scaffold density are precisely controlled by rotating a mandrel along one axis, translation along that same axis, and rotation around the second axis perpendicular to the electrospun fiber stream. The control is accomplished with a PC based "supervisory" control program written partially in the LabVIEW® programming language and partially in SI Programmer supplied by Applied Motion Products. Scaffold thickness and fiber diameters are determined by the syringe metering pump flow rate, material being electrospun and solution concentrations. Through extensive laboratory analysis (mechanical testing and both optical and electron microscopy), parameters such as fiber orientation, diameter and mechanics can be predictive from specific polymer setups. Our laboratory has demonstrated the ability to electrospin natural and synthetic polymers and this apparatus will be utilized to tailor scaffolds to meet specific tissue engineering needs by creating a truly biomimicking scaffold / extracellular matrix.

Orientadora: Profa. Dra. Sônia Maria Malmonge / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Engenharia Biomédica, 2014.

Nous étudions l'utilisation de l'électronique organique à l'interface du tissu nerveux pour des applications in vitro et in vivo. Le principal objectif est la fabrication d’interfaces neuronales flexibles pour enregistrer l'activité électrophysiologique de cellules neuronales sur de longues durées. À cette fin, nous utilisons du parylène-C comme substrat et le polymère conducteur poly(3,4-éthylène dioxythiophène):poly(styrène sulfonate) pour réduire l'impédance de l'interface cellule/électrode. En utilisant nos matrices de microélectrodes, nous montrons comment améliorer le rendement d'enregistrement avec un modèle 3D in vitro. La formation de clusters cellulaires 3D augmente considérablement le nombre d’enregistrements de potentiels d’action unitaires. In vivo, nous démontrons la fabrication de sondes de support en polymères biodégradables sur nos capteurs flexibles en utilisant une combinaison de polymères alcool polyvinylique et poly(lactique-co-glycolique). Alors que notre support d’insertion en PVA fournit la rigidité nécessaire à la pénétration, le revêtement PLGA retarde la dissolution du support afin de placer précisément les capteurs à l'intérieur du cerveau. Cela nous permet d’enregistrer en profondeur et, dans les conditions idéales, de minimiser les lésions cérébrales par rapport à les sondes traditionnelles rigides. Dans l'ensemble, nous avons réussi à effectuer des enregistrements électrophysiologiques avec nos propres microélectrodes et sondes invasives, améliorant le rendement d'enregistrements in vitro et démontrant que nos support d’insertion biodégradables pénètrent le cerveau. Ces résultats annoncent de prometteuses applications médicales futures. / Neural interfaces are designed to unravel the mysteries of the brain and to restore the functions of paralyzed patients. Despite the success of traditional neural interfaces, these rigid devices are prone to failure within months after surgery. Mechanical mismatch with the soft neural tissue is believed to be one of the main causes. In this thesis, we studied the use of soft organic electronics to interface with neural tissue for both in vitro and in vivo applications. Parylene-based microelectrode arrays (MEAs) and depth probes were made, employing the conducting polymer poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) to reduce the impedance at the cell-electrode interface. In vitro, we thereby showed how to enhance the recording yield of MEAs by creating a three-dimensional model of neurospheres. We further report on the fabrication of a new biodegradable polymer shuttle for flexible depth probes based on the combination of poly(vinyl alcohol) (PVA) and poly(lactic-co-glycolic) (PLGA). In vivo, the PVA/PLGA- shuttled probes were acutely tested in mice and revealed promising electrophysiological results. More research remains necessary to evaluate its long-term function in vivo. In conclusion, our results demonstrate that bioresorbable polymers are capable of providing the required stiffness to penetrate the brain, which shows much promise for future neural applications. This work thereby shows that a long-term functional neural interface is not far from being developed.

Introdução: A tomografia das artérias coronárias (ANGIO-TC) tem o potencial de medir as dimensões dos vasos e pode ser opção, aos métodos invasivos, para análises quantitativas em intervenções coronárias com suportes vasculares bioabsorvíveis (SVB) poliméricos radiolucentes. Objetivos: Medidas quantitativas pela ANGIO-TC do lúmen de segmentos coronários de pacientes submetidos a implante de um SVB com eluição de novolimus (DESolve®) foram comparadas às do ultrassom intracoronário (USIC). Os objetivos primários foram a comparação da área mínima e do volume do lúmen do SVB. Outros objetivos incluíram medidas nas margens do dispositivo, de referências do vaso e dos percentuais de estenose do SVB. A precisão de identificação do local de menor dimensão foi estimada pela distância entre este e a borda proximal do SVB. Método: Vinte e um pacientes submetidos a implante de um SVB DESolve e que foram reestudados após 6 meses com cinecoronariografia e USIC realizaram, também, ANGIO-TC. Sem conhecimento dos valores um do outro, um operador, em cada método, efetuou as medidas de volume, área e diâmetro mínimos do lúmen do SVB, de áreas e diâmetros mínimos do lúmen nas margens proximal e distal do SVB, de diâmetros e áreas de referência luminais e dos percentuais de estenose de diâmetros e áreas do SVB. Diferenças entre as médias foram significativas quando testes resultaram o valor de p< 0,05. Coeficientes de correlação foram calculados e a concordância foi analisada pelo método de Bland-Altman. Resultados: Os métodos não se mostraram correlacionados ao medirem área mínima do lúmen do SVB e a ANGIO-TC subestimou significativamente os valores em relação ao USIC (diferença de médias= -1,27 mm2; p= 0,004). As medidas do volume do lúmen do SVB mostraram correlação (r= 0,58; p= 0,006) e foram equivalentes (diferença de mediana= 5,4 mm3; p= 0,14). Em ambas, houve ampla variabilidade entre as medidas (variação percentual do erro de 128% para a área e de 119% para o volume). Os métodos mostraram correlações significativas para todas as demais variáveis. As médias das medidas de diâmetros, pela ANGIO-TC, não mostraram diferenças significativas em relação ao USIC. A ANGIO-TC subestimou significativamente as medidas da área mínima do lúmen no segmento distal ao SVB (diferença= -1,09 mm2; p = 0,017) e da área de referência dos vasos (diferença = -1,34 mm2; p = 0,008). Apesar do viés mínimo, os métodos mostraram ampla variação ao identificar o ponto de menor dimensão do SVB (erro percentual = 186%). A ANGIO-TC, assim como o USIC, não identificou casos de reestenose. Os métodos mostraram melhor nível de concordância ao medirem diâmetros e maiores discrepâncias ao estimarem percentuais de estenose. Conclusões: Em segmentos coronários com SVB polimérico, a ANGIOTC não obteve correlação e subestimou a área mínima do lúmen em relação ao USIC. Quantificações do volume do lúmen foram equivalentes e correlacionadas. Independentemente do nível de correlação, o padrão de concordância das medidas evidenciou um nível de acurácia insatisfatório para a ANGIO-TC substituir o USIC para quantificações de lumens em estudos com SVB radiolucentes, embora permaneça útil para análises visuais na prática clínica. / Computed tomography coronary angiography (CTA) is able to quantify vessel dimensions and might potentially be an alternative to substitute invasive methods for quantitative analysis in percutaneous coronary interventions with bioresorbable vascular scaffolds (BVS). This study compared quantitative measurements derived from CTA images to intravascular ultrasound (IVUS) in coronary segments implanted with radiolucent DESolve(TM) novolimuseluting BVS. Primary objectives were comparisons of BVS minimal luminal area and luminal volume in BVS. Secondary objectives included comparisons of minimal luminal areas and diameters in proximal and distal segments to the BVS, luminal vessel reference areas and diameters and BVS percent area and diameter stenosis. Precision of identifying BVS luminal minimal area were assessed by measuring distance from this point to proximal BVS border. Twenty-one patients underwent both CTA and IVUS, six months after BVS deployment. Each method was performed by an experienced operator, blinded to other\'s quantifications. Correlation coefficients were calculated and mean differences with 95% limits of agreement were assessed by Bland-Altman analysis. A p-value less than 0.05 were considered statistically significant. CTA did not show correlation to IVUS and significantly underestimated minimal luminal area in BVS (mean differences = -1.27 mm2; p = 0.004). Quantitative measurements of luminal volume in BVS were equivalent (median difference = 5.4 mm3; p = 0.14) and showed modest correlation (r= 0.58; p= 0.006). Both variables showed wide limits of agreement (percent error = 128% in minimal luminal area and 119% in luminal volume). Correlations were significant in all other variables. Both methods did not show significant differences quantifying all-segment diameters, and percent area and diameter stenosis. CTA significantly underestimated measurements of minimal luminal area in distal segment after BVS (mean difference = -1,09 mm2; p = 0,017) and luminal reference area (mean difference = -1,34 mm2; p = 0,008). CTA and IVUS showed nonsignificant bias to identify BVS luminal minimal area, but very wide limits of agreement (percent error= 186%). Both methods agreed in showing no cases of binary restenosis. Regardless of correlations or mean differences, all measures showed high variability, caracterized by wide limits of agreement. The least variations resulted from diameter quantifications, whereas estimated percent stenosis presented more disparities. These discrepancies between both methods showed that CTA analysis is still not fully developed to replace IVUS in the assessment of quantitative measurements in vessels treated with BVS. It remains, however, clinically useful for visual qualitative analysis.

Introdução: A tomografia das artérias coronárias (ANGIO-TC) tem o potencial de medir as dimensões dos vasos e pode ser opção, aos métodos invasivos, para análises quantitativas em intervenções coronárias com suportes vasculares bioabsorvíveis (SVB) poliméricos radiolucentes. Objetivos: Medidas quantitativas pela ANGIO-TC do lúmen de segmentos coronários de pacientes submetidos a implante de um SVB com eluição de novolimus (DESolve®) foram comparadas às do ultrassom intracoronário (USIC). Os objetivos primários foram a comparação da área mínima e do volume do lúmen do SVB. Outros objetivos incluíram medidas nas margens do dispositivo, de referências do vaso e dos percentuais de estenose do SVB. A precisão de identificação do local de menor dimensão foi estimada pela distância entre este e a borda proximal do SVB. Método: Vinte e um pacientes submetidos a implante de um SVB DESolve e que foram reestudados após 6 meses com cinecoronariografia e USIC realizaram, também, ANGIO-TC. Sem conhecimento dos valores um do outro, um operador, em cada método, efetuou as medidas de volume, área e diâmetro mínimos do lúmen do SVB, de áreas e diâmetros mínimos do lúmen nas margens proximal e distal do SVB, de diâmetros e áreas de referência luminais e dos percentuais de estenose de diâmetros e áreas do SVB. Diferenças entre as médias foram significativas quando testes resultaram o valor de p< 0,05. Coeficientes de correlação foram calculados e a concordância foi analisada pelo método de Bland-Altman. Resultados: Os métodos não se mostraram correlacionados ao medirem área mínima do lúmen do SVB e a ANGIO-TC subestimou significativamente os valores em relação ao USIC (diferença de médias= -1,27 mm2; p= 0,004). As medidas do volume do lúmen do SVB mostraram correlação (r= 0,58; p= 0,006) e foram equivalentes (diferença de mediana= 5,4 mm3; p= 0,14). Em ambas, houve ampla variabilidade entre as medidas (variação percentual do erro de 128% para a área e de 119% para o volume). Os métodos mostraram correlações significativas para todas as demais variáveis. As médias das medidas de diâmetros, pela ANGIO-TC, não mostraram diferenças significativas em relação ao USIC. A ANGIO-TC subestimou significativamente as medidas da área mínima do lúmen no segmento distal ao SVB (diferença= -1,09 mm2; p = 0,017) e da área de referência dos vasos (diferença = -1,34 mm2; p = 0,008). Apesar do viés mínimo, os métodos mostraram ampla variação ao identificar o ponto de menor dimensão do SVB (erro percentual = 186%). A ANGIO-TC, assim como o USIC, não identificou casos de reestenose. Os métodos mostraram melhor nível de concordância ao medirem diâmetros e maiores discrepâncias ao estimarem percentuais de estenose. Conclusões: Em segmentos coronários com SVB polimérico, a ANGIOTC não obteve correlação e subestimou a área mínima do lúmen em relação ao USIC. Quantificações do volume do lúmen foram equivalentes e correlacionadas. Independentemente do nível de correlação, o padrão de concordância das medidas evidenciou um nível de acurácia insatisfatório para a ANGIO-TC substituir o USIC para quantificações de lumens em estudos com SVB radiolucentes, embora permaneça útil para análises visuais na prática clínica. / Computed tomography coronary angiography (CTA) is able to quantify vessel dimensions and might potentially be an alternative to substitute invasive methods for quantitative analysis in percutaneous coronary interventions with bioresorbable vascular scaffolds (BVS). This study compared quantitative measurements derived from CTA images to intravascular ultrasound (IVUS) in coronary segments implanted with radiolucent DESolve(TM) novolimuseluting BVS. Primary objectives were comparisons of BVS minimal luminal area and luminal volume in BVS. Secondary objectives included comparisons of minimal luminal areas and diameters in proximal and distal segments to the BVS, luminal vessel reference areas and diameters and BVS percent area and diameter stenosis. Precision of identifying BVS luminal minimal area were assessed by measuring distance from this point to proximal BVS border. Twenty-one patients underwent both CTA and IVUS, six months after BVS deployment. Each method was performed by an experienced operator, blinded to other\'s quantifications. Correlation coefficients were calculated and mean differences with 95% limits of agreement were assessed by Bland-Altman analysis. A p-value less than 0.05 were considered statistically significant. CTA did not show correlation to IVUS and significantly underestimated minimal luminal area in BVS (mean differences = -1.27 mm2; p = 0.004). Quantitative measurements of luminal volume in BVS were equivalent (median difference = 5.4 mm3; p = 0.14) and showed modest correlation (r= 0.58; p= 0.006). Both variables showed wide limits of agreement (percent error = 128% in minimal luminal area and 119% in luminal volume). Correlations were significant in all other variables. Both methods did not show significant differences quantifying all-segment diameters, and percent area and diameter stenosis. CTA significantly underestimated measurements of minimal luminal area in distal segment after BVS (mean difference = -1,09 mm2; p = 0,017) and luminal reference area (mean difference = -1,34 mm2; p = 0,008). CTA and IVUS showed nonsignificant bias to identify BVS luminal minimal area, but very wide limits of agreement (percent error= 186%). Both methods agreed in showing no cases of binary restenosis. Regardless of correlations or mean differences, all measures showed high variability, caracterized by wide limits of agreement. The least variations resulted from diameter quantifications, whereas estimated percent stenosis presented more disparities. These discrepancies between both methods showed that CTA analysis is still not fully developed to replace IVUS in the assessment of quantitative measurements in vessels treated with BVS. It remains, however, clinically useful for visual qualitative analysis.

Une série d'homopolymères tels que poly(L-lactide) (PLLA), poly(triméthylène carbonate) (PTMC), poly (e-caprolactone) (PCL) et les copolymers ont été synthétisés par polymérisation par ouverture de cycles de monomère appropriés en utilisant du zinc lactate ou octanoate d'étain comme catalyseur. Leurs propriétés thermiques, dégradation hydrolytique, dégradation enzymatique, propriétés mécaniques et comportement à mémoire de forme ont été étudiées à l'aide de DSC, RMN, SEC, ESEM, DMA et machine à traction Instron. Les copolymères de triméthylène carbonate et DL-lactide (PTDLA) peuvent être dégradés non seulement par simple hydrolyse, mais aussi par la protéinase K. Le copolymère PTDLA composé de 50/50 TMC/LA est très élastique, Tg servant de température de transition entre les formes temporaire et permanente. Le PTMC ne peut pas être dégradé par simple hydrolyse ou par la protéinase K, mais peut être dégradé par les lipases de Candida Antarctica et Hog Pancreas. La biocompatibilité des PLLA, PTMC, PCL, PTLLA, PTDLA et PTCA a été évaluée par des expériences d'hémolyse, adhésion des plaquettes, MTT et culture cellulaire. Les résultats montrent des tous les polymères présentent très bonnes propriétés hémolytiques et anti-coagulantes, bonne adhésion, propagation et prolifération des cellules. / A series of homopolymers such as poly(L-lactide) (PLLA), poly(trimethylene carbonate) (PTMC), poly(e-caprolactone) (PCL) and various copolymers were synthesized by ring opening polymerization of appropriate monomer feeds using zinc lactate or stannous octoate as catalyst. Their thermal properties, hydrolytic degradation, enzymatic degradation, mechanical properties and shape memory behavior were investigated by using DSC, NMR, SEC, ESEM, DMA and Instron tensile instrument. Among the various polymers, copolymers of trimethylene carbonate and DL-lactide (PTDLA) can be degraded not only by pure hydrolysis, but also by proteinase K. PTDLA composed of the same TMC and LA contents is highly elastic, Tg acting as the switch temperature between temporary and permanent shapes. PTMC cannot be degraded by pure hydrolysis or by proteinase K, but can be degraded by lipases from Candida Antarctica or Hog Pancreas. The biocompatibility of PLLA, PTMC, PCL, PTLLA, PTDLA and PTCA was evaluated from haemolysis experiments, platelet adhesion, MTT assay and cell culture. The results showed that all the polymers present outstanding haemolytic and anti-coagulant properties, and good cellular adhesion, spreading and proliferation.

No description available.

No description available.

Les bioresorbable stents (BRS), en français intitulés tuteurs coronariens biorésorbables, sont constitués d’un polymère biorésorbable, plutôt que de métal, et ne créent pas d’artéfacts métalliques significatifs en tomodensitométrie (TDM). Cela permet une meilleure évaluation de la plaque coronarienne sous ces tuteurs en TDM qu’avec les anciens tuteurs qui sont en métal. OBJECTIF: Évaluer l’évolution de la composition de la plaque, sa fraction lipidique (FL)— marqueur de vulnérabilité de la plaque, dans les 3 zones pré-tuteur (bord proximal), intra-tuteur et post-tuteur (bord distal), et le volume de la plaque entre 1 et 12 mois post-implantation de BRS. MÉTHODOLOGIE: Il s’agit d’une étude observationnelle longitudinale réalisée chez 27 patients consécutifs (âge moyen 59,7 +/- 8,6 ans) et recrutés prospectivement pour une imagerie par TDM 256-coupes à 1 et 12 mois post-implantation de BRS (35 tuteurs total). Les objectifs primaires sont: volume de plaque totale et de FL (mm3) comparés entre 1 et 12 mois. Afin de tenir compte de la corrélation intra-patient, des analyses de variance des modèles linéaires mixtes avec ou sans spline sont utilisés avec deux facteurs répétés temps et zone/bloc (1 bloc= 5 mm en axe longitudinal). La valeur % FL= volume absolu du FL/ volume total de la plaque. RÉSULTATS: Notre analyse par bloc ou par spline n’a pas démontré une différence significative dans les volumes de plaque ou des FL dans les zones pre- intra- and post-tuteur entre 1 et 12 mois. CONCLUSION: Notre étude a réussi à démontrer la faisabilité d’une analyse non-invasive quantitative répétée de la plaque coronarienne et de la lumière intra-tuteur avec l’utilisation de TDM 256 coupes. Cette étude pilote n’a pas démontré de différence significative dans les volumes des plaques et atténuation entre 1- et 12- mois de follow-up post-implantation de BRS. Notre méthode pourrait être appliquée à l’évaluation des différents structures ou profils pharmacologiques de ces tuteurs. / Coronary bioresorbable stents (BRS) are made of a bioresorbable polymer rather than metal. Unlike metallic stents, BRS do not produce significant artifacts in computed tomography (CT) and are radiolucent in CT, making it possible to evaluate coronary plaque beneath an implanted stent. PURPOSE: The purpose of our study was to evaluate the volumes of plaque and low attenuation plaque components (LAP —a marker of plaque vulnerability) of pre-, intra- and post-stent plaque location between 1 and 12 months post-implantation. METHODS: In our prospective longitudinal study, we recruited 27 consecutive patients (mean age 59.7 +/- 8.6 years) with bioresorbable stents (n=35) for a 256-slice ECG-synchronized CT evaluation at 1 month and at 12 months post stent implantation. Total plaque volume (mm3) as well as absolute and relative (%) LAP volume per block in the pre-, intra- and post-stent zones were analyzed; comparison of 1 and 12 months post BRS implantation. Changes in these variables were assessed using mixed effects models with and without spline, which also accounted for correlation between repeated measurements with factors such as time and zone/block (1 block = 5 mm in longitudinal axis). The value % LAP= LAP absolute volume/ total plaque volume. RESULTS: Our block or spline model analysis showed no significant difference in plaque or LAP volumes in pre-, intra- and post-stent zones measured at 1 month and at 12 months. CONCLUSION: Our study demonstrates the feasibility of repeated non-invasive quantitative analysis of intrastent coronary plaque and in-stent lumen using a 256-channel CT scan. This pilot study did not show significant differences in plaque volume and attenuation between 1- and 12-month follow-up from stent implantation. The method we used could be applied to the evaluation of different stent structures or different pharmacological profiles of bioresorbable stents.