Dry eye syndrome has been associated with the lack of phospholipids in the tear film, leading to disruption of the tear film and subsequent irritation. Characterization of the transport and release of phospholipids from a silicone hydrogel contact lens is required to assess the possible use of these lenses for phospholipid delivery to increase patient comfort. This thesis examines the use of silicone hydrogel contact lenses as phospholipid delivery devices. Contact lenses of silicone hydrogel composition were loaded with varying amounts of radiolabeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) from a solution of n-propanol. These lenses were eluted at 35°C into artificial tear fluid (ATF) or ATFcontaining varying amounts of DMPC. The amount of DMPC loaded into a lens is a linear function of the time of exposure to the DMPC/propanol solution. The initial rate of elution into ATF appears to be diffusion controlled for at least 10 hrs and is proportional to the amount of DMPC loaded. The ease of loading and the controllable release of DMPC from silicone hydrogels present the possibility of using such lenses to counter eye discomfort caused by inherently low levels of phospholipid in tears. To reduce manufacturing steps and concern for residual n-propanol in the lens, it is beneficial to incorporate the DMPC into the monomer formulation and then photopolymerize the lens. Results showed that using this process, DMPC can be placed in the lens and then eluted at faster rates than when it was loaded from n-propanol.

Various silicone elastomers have been evaluated for use in the prosthetic reconstruction of facial defects. Their strength, texture, flexibility, hardness, ease of preparation, pigment receptivity and retention, and their resistance to cleaning were compared and the data consulted when an elastomer was chosen to restore defects, improve aesthetics and reestablish the confidence of a selection of patients. Detailed case reports are provided, together with information on the adhesives or mechanical methods available for retaining the facial prosetheses. Cyanoacrylate adhesives for use on skin surfaces and as tissue adhesives have been studied in detail. A novel n-butyl 413 cyanoacrylate has been developed with a viscosity, haemostatic property and stability to make it particularly suitable for use in skin grafting and tissue repair. It has already been used with good results on patients with severe burns. An improved formulation, containing a fluorescent dye, can be precisely applied through a specially constructed foot-controlled dispenser illuminated by a fibre-optic supplying UV-light. Cyanoacrylates are already being used as tissue adhesives in place of the conventional but potentially disfiguring suture. The availability of improved, imperceptible adhesives and a precision applicator, which can be used in a modern operating theatre, will extend their effectiveness and satisfy some of the needs of Plastic, and Oral and Maxillo-Facial Surgeons. Portable applicators have potential use in battlefield and in veterinary surgery and overcome the imprecision characteristic of earlier methods. / Loctite UK

Silicone polymers and network-materials have proven extremely useful in a variety of applications owing to their superb properties when compared to carbon-based polymers. Polysiloxanes containing functional groups other than simple alkyl moieties have allowed for further manipulations of pendant groups along the polymer backbone leading to a greater range of possible chemical transformations, as well as changes in physical/interfacial properties. One aspect of functional polymers that has yet to be explored with respect to primarily silicone-based systems is that of stimuli-responsive materials. In order for this unique application to work, silicones must be functionalized with a group or groups that can influence the polymer’s properties based on that group’s response to specific external stimuli. Boronic acids represent one such group, wherein the most common stimuli used to affect changes in ionization state and solubility are pH and diol-binding. Boronic acids are also capable of forming weak hydrogen-bonded dimers with other boronic acids, and dynamic covalent bonds with Lewis bases. It is proposed that the covalent attachment of boronic acids and their derivatives onto silicones could lead to stimuli-responsive silicone materials. Herein, the synthesis of silicone-boronic acids and their protected boronic esters is described. The simple two-step method involving boronic acid protection followed by hydrosilylation has led to a variety of molecules differing in molecular weight and three-dimensional geometry through the use of commercially available hydride-functional silicones. Initial results regarding saccharide binding selectivity and the impacts on silicone solubility are provided. The unique interfacial behaviour of silicone-boronic esters and their propensity to form self-assembled, crosslinked films at an air/water interface are also reported. Using several different diol protecting groups and a variety of aqueous sub-phases, the mechanism for changes in physical properties as well as crosslinking were revealed. Finally, the production of new thermoplastic silicone elastomers from silicone-boronic esters and amine-containing molecules is discussed. The Lewis acid/Lewis base complexation that occurs between nitrogen and boron can provide enough strength to produce robust, yet recyclable, silicone elastomers without the use of catalyst or solvent. Elastomers can be easily dissolved and reformed through the introduction and removal of a mono-functional Lewis base. The impact of crosslink density, controlled by the quantities and molecular weights of each polymer component used, on physical characteristics is reported. / Thesis / Doctor of Philosophy (PhD)

Le cancer du col de l’utérus, le quatrième cancer le plus répandu chez la femme, affecte principalement les régions à faible et moyen revenu. Alors que les taux d’incidence et de mortalité sont les plus élevés dans les pays en développement, l’accessibilité aux systèmes de dépistage et traitement y est limitée. La curiethérapie (BT) à haut débit de dose (HDR) fait partie du traitement standard recommandé pour les cancers du col de l’utérus en stade localement avancé IIIB-IVA. Les applicateurs commerciaux pour les traitements de BT combinés intracavitaire et interstitiel (IC/IS) sont très chers et n’offrent que des positions et orientations fixes pour les aiguilles IS. L’applicateur à demi anneaux Montréal (MSR) propose la modification d’un applicateur IC commercial par l’ajout de capuchons Adaptiiv, imprimés 3D à faible coût avec la technologie de photopolymérisation (SLA) en résine stérilisable et biocompatible, permettant l’intégration et l’optimisation d’un maximum de 10 trajectoires IS. Dans cette étude, une nouvelle génération de capuchons réduit le diamètre de l’applicateur MSR d’au plus 8.4 mm et introduit quatre positions d’aiguilles IS additionnelles à l’intérieur du demi anneau (SR), deux positions par SR. Ces capuchons sont imprimés avec la résine BioMed Clear sur l’imprimante SLA Form3B (Formlabs Inc., Massachusetts, États-Unis) et accommodent des angles d’aiguilles IS allant jusqu’à 45°. Les erreurs sur les trajectoires des aiguilles IS de l’applicateur MSR avec les nouveaux capuchons sont évaluées dans un fantôme gynécologique (GYN), développé dans le cadre de ce projet, et comparées dans une analyse statistique aux performances de l’applicateur Venezia (Elekta, Stockholm, Suède). Le fantôme GYN développé comprend une masse implantable en silicone, dont la texture est optimisée avec l’expérience clinique de deux radio-oncologistes spécialisées en BT GYN pour simuler l’insertion d’implants cliniques, pouvant supporter un grand nombre d’aiguilles IS. L’étude sur ce fantôme a démontré que la performance de l’un des capuchons de la nouvelle génération ne présente pas de différence statistiquement et cliniquement significative avec l’applicateur Venezia. Les performances de ce capuchon sont reproductibles dans les différents milieux en silicone et en utilisant différents types d’aiguilles IS. / Cervical cancer, the fourth most common cancer in women, mainly affects low- and middleincome regions. While incidence and mortality rates are highest in developing countries, the accessibility to screening and treatments is limited in those regions. High dose rate (HDR) brachytherapy (BT) is part of the standard of care recommended for locally advanced cervical cancer. Commercial applicators for combined intracavitary-interstitial (IC/IS) BT treatments are very expensive and only offer fixed IS needle positions and orientations. The Montreal split ring (MSR) applicator modifies the CT/MR split-ring IC applicator by the addition of Adaptiiv caps, 3D printed at low cost with stereolithography apparatus (SLA) technology in biocompatible and sterilizable resin in order to allow integration and optimization of up to 10 IS trajectories. In this study, a new generation of caps reduces the diameter of the MSR applicator by at most 8.4 mm and introduces four additional IS needle positions inside the split ring (SR), two positions per SR. These caps are 3D printed using BioMed Clear resin on the Form3B (Formlabs Inc., Massachusetts, USA) SLA printer and accommodate up to 45° IS needle angles. The errors on the IS needle trajectories of the MSR applicator with the new caps are evaluated in a gynecological (GYN) phantom, developed within the framework of this project, and compared in a statistical analysis to the performance of the Venezia applicator (Elekta, Stockholm, Sweden). The developed GYN phantom includes an implantable silicone structure, optimized according to the feedback of two radiation oncologists specialized in GYN BT to simulate clinical implants insertion, which can support a large number of IS needles. The study on this phantom showed that the performance of one of the caps from the new generation does not present a statistically and clinically significant difference with the Venezia applicator. The performance of this cap is reproducible in different silicone media and using different IS needle types.

3D printing technology, which has its origins in rapid prototyping, is increasingly used to build functional devices. Although 3D printing technology has been well developed for thermoplastic polymers and metals, it is still in the research phase for soft polymeric materials such as silicones. Silicones are an industrially vital polymer characterized by a broad spectrum of chemical and physical properties for several smart applications, including on skin printing, smart sensors, multigradient material, and soft actuators. Extrusion-based multimaterial printing is one of the 3D printing techniques that have been adapted due to its compatibility to process silicone-based materials for constructing various functional devices. However, there are several challenges such as achieving on the fly mixing at low Reynolds numbers regime, achieving fast switching while using Newtonian/non-Newtonian inks, and achieving multimaterial printing on nonplanar surfaces. The development of suitable and robust printheads that are able to tackle those challenges can expand the application of this technology to a wide range of fields. In this thesis, several deposition-controlled printhead designs have been created for 3D printing multifunctional devices using an understanding of microfluidics. The established printhead can be controlled to formulate different multigradient structures through on the fly mixing during the material printing. Moreover, the developed printhead can be adapted to print multi viscous inks with high switching rates up to 50 Hz. Through the developed system, the printhead was able to track topologies in real-time, allowing objects to be printed over complex substrates. These new capabilities were applied to fabricate functional structures in order to demonstrate the potential of the developed printhead approaches that can be used in various applications, including smart sensors, soft robotics and multigradient objects. / Thesis / Doctor of Philosophy (PhD) / 3D printing techniques, such as extrusion-based multimaterial printing, have recently been utilized to process silicones due to their versatility in different smart applications, including multigradient material and soft actuators. Although it represents significant progress, there are still several challenges, including the proper mixing during printing with a laminar flow regime, the fast switching between different inks, and the printing over complex topographies. Therefore, various printhead designs have been developed in this thesis to tackle these challenges. In particular, a mixer printhead has been designed to allow mixing during printing for building multigradient objects. Also, a scalable printhead has been developed to allow fast switching for creating pixelated structures. Finally, a simple mechanical system has achieved multimaterial printing over various nonplanar surfaces. To the best of the author's knowledge, the developed printheads can be used in many fields, such as soft robotics and smart devices.

Biochip technology is highly effective method that allows monitoring of biomaterials e.g., yeast and bacteria at a time in computerized automatic operations. Miniaturized nanostructure p-n junction test sites, which are arranged on a solid substrate, are proposed to sense and count the biomaterials. This PhD thesis reports on the impedance of p-n junction-based Si biochips with gold ring top electrodes and unstructured gold bottom electrodes, which allows for counting target biomaterial in a liquid-filled ring top electrode region. The phosphor and boron implanted biochips prepared in dissimilar annealing and doping conditions have been considered and three different types of top electrodes designed and tested to check the influence of the properties of the top electrode on the biochips to achieve more convenient samples for bio sensing technology. The systematic experiments on p-n junction-based Si biochips fabricated by two different sets of implantation parameters (i.e., biochips PS5 and BS5) are studied and the comparable significant change of impedance characteristics in the biochips in dependence on the number of bacteria suspensions, i.e., Lysinibacillus sphaericus JG-A12, in Deionized water at optical density at 600 nm from OD600 = 4–16 in the electrode ring region is demonstrated. The number of biomaterials and the microscopic images can be linked to the impedance changes of the biochip. The electrical equivalent circuit models for the devices have been proposed by using characterized frequency dependent capacitance and conductance of biochips. While the Nyquist spectrum of the biochips are not compromise on perfect semicircle, combination of constant phase elements with resistor in parallel fashion and series inductor and resistor have been utilized to model the impedance of the biochips. Corresponding parameters i.e., capacitors, resistors and inductors have been extracted from the modeling results and the changes in their values by adding the biomaterials obtained. As the result, the linear relation between the numbers of the biomaterial and the impedance of the biochips has been showed. Furthermore, Deionized water and glucose with yeast (Saccharomyces cerevisiae) at optical density OD600 ranging from 4 to 16 has been put in the ring electrode region of impedance biochips and impedance has been measured in dependence on the added volume (20, 21, 22, 23, 24, 25 µL). Modeled impedance of the biochip reveals a linear relationship between the impedance model parameters and yeast concentration. Presented biochips allow for continuous impedance measurements without interrupting the cultivation of the yeast. A multiparameter fit of the impedance model parameters allows to determine the concentration of yeast cy in the range from cy = 3.3x10^7 to cy = 17x10^7 cells/mL. This work shows that independent on the liquid, DI water or glucose, the change of the impedance model parameters with increasing added volume of the liquid is clearly distinguishable from the change of impedance model parameters with increasing concentration of added yeast in the ring electrode region of the impedance biochips. We also counted bacterial cells of E. coli strain K12 in several-microliter DI water or in several-microliter PBS at the low optical density (OD) range (OD = 0.05–1.08) in contact with the surface of Si-based impedance biochips with ring electrodes by impedance measurements. The multiparameter fit of the impedance data allowed calibration of the impedance data with the concentration cb of the E. coli cells in the range of cb = 0.06 to 1.26 × 10^9 cells/mL. The results showed that for E. coli in DI water and in PBS, the modelled impedance parameters depend linearly on the concentration of cells in the range of cb = 0.06 to 1.26 × 10^9 cells/mL, whereas the OD, which was independently measured with a spectrophotometer, was only linearly dependent on the concentration of the E. coli cells in the range of cb = 0.06 to 0.50 × 10^9 cells/mL. with the help of the newly developed ring electrode structure, the modeled capacitance and resistance parameters of the electrical equivalent circuit describing the p-n junction-based biochips depend linearly on the number of bacteria in the ring top electrode region, which successfully proves the potential performance of p-n junction-based Si biochips in observing the bacterial suspension. The proposed p-n junction-based biochips reveal perspective applications in medicine and biology for diagnosis, monitoring, management, and treatment of diseases.

In this dissertation, four test approaches were developed to characterize the adhesion performance and durability of adhesive bonds for specific applications in areas spanning from structural adhesive joints to popular confectionaries such as chewing gum. In the first chapter, a double cantilever beam (DCB) specimen geometry is proposed for combinatorial fracture studies of structural adhesive bonds. This specimen geometry enabled the characterization of fracture energy vs. bondline thickness trends through fewer tests than those required during a conventional "one at a time" characterization approach, potentially offering a significant reduction in characterization times. The second chapter investigates the adhesive fracture resistance and crack path selection in adhesive joints containing patterns of discreet localized weak interfaces created using physical vapor deposition of copper. In a DCB specimen tested under mode-I conditions, fracture energy within the patterned regions scaled according to a simple rule of mixture, while reverse R-curve and R-curve type trends were observed in the regions surrounding weak interface patterns. Under mixed mode conditions such that bonding surface with patterns is subjected to axial tension, fracture energy did not show R-curve type trends while it was observed that a crack could be made to avoid exceptionally weak interfaces when loaded such that bonding surface with defects is subjected to axial compression. In the third chapter, an adaptation of the probe tack test is proposed to characterize the adhesion behavior of gum cuds. This test method allowed the introduction of substrates with well-defined surface energies and topologies to study their effects on gum cud adhesion. This approach and reported insights could potentially be useful in developing chewing gum formulations that facilitate easy removal of improperly discarded gum cuds from adhering surfaces. In the fourth chapter we highlight a procedure to obtain insights into the long-term performance of silicone sealants designed for load-bearing applications such as solar panel support sealants. Using small strain constitutive tests and time-temperature-superposition principle, thermal shift factors were obtained and successfully used to characterize the creep rupture master curves for specific joint configurations, leading to insights into delayed failures corresponding to three years through experiments carried out in one month. / Ph. D.

As infecções causadas por leveduras representam um grave problema em Saúde Pública. O objetivo desta pesquisa é o estudo aderência de Candida spp. (C. albicans ATCC18804, C. albicans SC5314, C. albicans cepa de campo, C. glabrata ATCC2001) sobre cateter urinário de Látex siliconizado (LS) e Silicone total (ST); avaliação da sensibilidade ao M-EDTA® dos biofilmes formados e quantificação dos genes ALS1 e ALS3 expressos por células sésseis de C. albicans. Os biofilmes de Candida spp. foram produzidos sobre cateteres urinários (LS e ST) segmentados em 1,0 cm de comprimento e separadamente introduzidos em poços de placas de poliestireno, sendo incubados a 35±1°C em contato com as suspensões de leveduras por 6, 24 e 48 e 72 horas. Os segmentos de cateter foram examinados por MEV, por cultura microbiológica, para avaliação da viabilidade celular e redução do sal de tetrazólio (XTT), para medir a atividade metabólica das células em biofilme. A sensibilidade das células sésseis ao M-EDTA® foi determinada após a exposição dos biofilmes ao produto; a expressão dos genes ALS1 e ALS3 de C. albicans SC5314 foi analisada por reação em cadeia de polimerase quantitativo (qPCR) e o resultado da recuperação de células viáveis de biofilme de Candida spp. foi expresso em log média ± desvio-padrão. Do biofilme de C. albicans ATCC18804 formado sobre LS, a recuperação foi de 4,48±2,52 e sobre ST; 4,76±1,62. A média de recuperação do biofilme de C. albicans SC5314 sobre LS foi de 4,35±0,39 e sobre ST, de 4,21±0,22. Para C. albicans cepa de campo, a média no LS foi 5,15±0,18 e no ST; 4,79±0,17. Do biofilme de C. glabrata ATCC2001 formado sobre o LS, a recuperação média foi de 4,69±0,19 e sobre ST, de 4,75±0,68. A atividade metabólica das células em biofilme foi expressa em valores de absorbância. Células de C. albicans ATCC18804 aderidas ao LS apresentaram atividade de 0,070±0,06 e sobre ST; 0,0681±0,06. A atividade metabólica do biofilme de C. albicans SC5314 sobre o LS foi de 0,0622±0,05 e sobre ST; 0,0785±0,05. Das células de C. albicans cepa de campo aderidas ao LS detectou-se atividade de 0,1064±0,01 e sobre ST, de 0,904±0,03. Células de C. glabrata ATCC2001 aderidas ao LS apresentaram uma atividade de 0,0785±0,04 e sobre ST; 0,0755±0,03. A observação ao MEV mostrou células leveduriformes de C. albicans SC5314 aderidas ao LS e ao ST formando monocamadas. Candida albicans ATCC18804, C. albicans cepa de campo e C. glabrata ATCC2001 formaram monocamadas de células leveduriformes e produziram filamentos sobre a superfície LS e ST, sugerindo uma estrutura tridimensional do biofilme. A exposição ao M-EDTA® dos biofilmes de C. albicans ATCC18804, C. albicans SC5314, C. albicans cepa de campo e C. glabrata ATCC2001 mostrou que os mesmo foram sensíveis à ação do produto. Após o crescimento de C. albicans SC5314 em biofilme, não houve detecção de expressão dos genes ALS1 e ALS3. Em conclusão, todas as espécies de Candida formaram biofilme sobre os biomateriais. Os biofilmes foram sensíveis a ação do M-EDTA® e C. albicans SC5314 não expressou os genes ALS1 e ALS3. / Infections caused by yeasts represent a serious problem in Public Health. The aim of this research was to study the Candida spp. (C. albicans ATCC18804, C. albicans SC5314, C. albicans wild type, C. glabrata ATCC2001) attachment onto urinary catheters made of Siliconized latex (LS) and Total silicon (ST); evaluating the susceptibility of biofilms to M-EDTA® and quantifying genes ALS1 and AL3 expressed by sessile cells of C. albicans. The Candida spp. biofilms were produced over the surface of urinary catheters (LS and ST). The catheters were cut in 1.0cm in length, introduced in wells of polystyrene plates and incubated at 35±1°C in contact with yeasts suspensions during 6, 24, 48 and 72 hours. The catheter samples were examined by SEM, by microbiology culture to evaluate the viable cells and reduction of tetrazolium salt (XTT) to measure the metabolic activity of Candida spp. cells into biofilms. The sensitivity of sessile cells to M-EDTA® was determinated after the exposition of biofilms to the product. The C. albicans SC5314 expression of ALS1 and ALS3 genes was analyzed by quantitative polymerase chain reaction (qPCR). The results of Candida spp. viable cells recovery were determined in log average ± standard deviation. From C. albicans ATCC18804 biofilm cells formed onto LS, the recovery was 4.48±2.52 e onto ST; 4.76±1.62. The average of recovery from C. albicans SC5314 biofilm formed onto LS was 4.35±0.39 and onto ST; 4.21±0.22. For C. albicans wild type, the recovery onto LS was 5.15±0.18 and above ST; 4.79±0.17. C. glabrata ATCC2001 biofilm formed onto LS, the medium was 4.69±0.19 and onto ST; 4.75±0.68. The metabolic activity from cells into biofilms was determined in absorbance values. C. albicans ATCC18804 cells attachment on LS had an activity of 0.070±0.06 and on ST; 0.0681±0.06. The metabolic activity of C. albicans SC5314 biofilm formed onto LS was 0.0622±0.05 and onto ST; 0.0785±0.05. From C. albicans wild type attached onto LS, the activity detected was 0.1064±0.01 and on ST; 0.904±0.03. C. glabrata ATCC2001 cells attached on LS had an activity of 0.0785±0.04 and on ST; 0.0755±0.03. The SEM observations showed C. albicans SC5314 yeast cells attached on LS and ST forming a monolayer. C. albicans ATCC18804, C. albicans wild type and C. glabrata ATCC2001 formed yeast monolayer and produced filaments over the surface of LS and ST, suggesting the three-dimensional structure of biofilm. The M-EDTA® exposition of C. albicans ATCC18804, C. albicans SC5314, C. albicans wild type and C. glabrata ATCC2001 showed that the biofilms were sensitive to the product action. After the C. albicans SC5314 biofilm growth, there was not expression of the ALS1 and ALS3 genes. In conclusion, all the Candida species formed biofilms on the biomaterials. The biofilms were sensitive to M-EDTA® and the C. albicans SC5314 didn´t express the ALS1 and ALS3 genes.

Objetivo: Avaliar a segurança e eficácia da injeção transesfincteriana de silicone para o tratamento da incontinência anal, assim como correlacionar os resultados clínicos, ultra-sonográficos e manométricos. Métodos: Pacientes incontinentes foram submetidos à manometria e ultra-sonografia anorretal, índice de incontinência (II) e instrumento de qualidade de vida (FIQL), antes e após injeção do silicone (PTQ) sob anestesia local e profilaxia antibiótica. Os critérios de inclusão foram: incontinência anal, lesão isolada ou múltipla do músculo esfíncter interno do ânus, associada ou não à lesão isolada, em um quadrante, do músculo esfíncter externo do ânus. O instrumento FIQL utilizado inclui quatro domínios: estilo de vida, comportamento,depressão e constrangimento.Os parâmetros da manometria foram: pressão média de repouso (PMR), pressão média (PMCV) e máxima (PmaxCV) de contração voluntária, zona de alta pressão (ZAP) e índice de assimetria (IA). Após três meses de tratamento, os pacientes foram reavaliados através do II, FIQL, manometria e ultra-sonografia anorretal. Um grupo controle composto por 10 homens e 10 mulheres continentes e sem história prévia de cirurgia anorretal foi submetido à manometria após consentimento informado. Resultados: Foram estudados 35 pacientes, 28 mulheres e sete homens com idade média de 60,3 (19-80) anos, antes e após injeção do silicone anal. As complicações observadas incluíram dois hematomas (5,7%), um abscesso anal (2,8%), dor anal em dois pacientes (5,7%) e dificuldade evacuatória em um paciente (2,8%). Notou-se uma melhora do índice médio de incontinência de 11,3 para 4,3 (p < 0,001). Houve melhora de todos os domínios estudados no instumento FIQL (p<0,0001). Pacientes incontinentes apresentaram hipotonia esfincteriana quando comparados aos controles (p < 0,05). As pressões esfincterianas antes e após injeção foram respectivamente: PMR (29,4 mmHg x 35,1 mmHg; p = 0,07), PMCV (68,6 mmHg x 75,9 mmHg; p = 0,20) e PmaxCV (102,2 mmHg x 127,0 mmHg; p = 0,11). Houve aumento médio da ZAP de 1,0 para 1,7 cm (p = 0,002) Em relação aos resultados da manometria: o IA aos 3 e 2 cm apresentou redução significativa após injeção do silicone (p < 0.05 e 0,002). A ultra-sonografia de canal anal demonstrou a presença do silicone nos sítios de injeção em todos os pacientes. Conclusão: Em casos selecionados, a injeção transesfincteriana de silicone é um método seguro e proporciona uma melhora do quadro de incontinência anal, observada pela mudança significativa dos parâmetros de qualidade de vida e índice de incontinência. O provável mecanismo de ação pelo qual o agente estudado melhora o quadro de incontinência parece relacionar-se à correção da assimetria esfincteriana e aumento do comprimento da zona de alta pressão. / Aim: To evaluate safety and efficacy of trans-sphincteric silicone injection for the treatment of anal incontinence and to assess correlation between clinical and physiological results. Methods: Incontinent patients prospectively selected by clinical and physiological evaluation underwent trans-sphincteric silicone injection (PTQ) under local anesthesia. Eight channel manometry with asymmetry index and anal ultrasound were performed before and after injections. Incontinence scale (IS) and quality of life instrument (FIQL scale) were applied before and after injection.Inclusion criteria were: anal incontinence, isolated or multiple injury of the internal anal sphincter associated or not to small, restricted, external anal sphincter defect. FIQL scale included four domains: life-style, behavior, depression and embarrassment. Manometry evaluation included mean resting pressure (MRP), mean squeeze pressure (MSP), maximal squeeze pressure (MaxSP), high-pressure zone (HPZ) and asymmetry index (AI). After 3 months of treatment the patients had been reevaluated through the IS, FIQL scale, manometry and ultrasound. A controlled group of 20 healthy volunteers (10 men and 10 women) underwent anal manometry. Results: 35 patients (28 women and seven men) with a mean age of 60.3 (19-80) years were evaluated. Complications observed were two anal hematomas (5,7%), one perianal abscess (2.8%), two patients complained of anal pain (5,7%) and one patient required assistance for defecation (2,8%). Mean incontinence score improved significantly after injection: 11, 3 to 4,3 (p < 0.001). Significant improvement in the FIQL scale was noticed in all domains (p < 0.0001). Incontinent patients had significantly lower anal pressures when compared to controls (p < 0.05). Manometric pressures before and after injection did not change: MRP (29,4 mmHg x 35,1 mmHg; p = 0.07), MSP (68,6 mmHg x 75,9 mmHg; p = 0.20) e MaxSP (102.2 mmHg x 127.0 mmHg; p = 0.11) The HPZ changed from 1 to 1,7 cm after injection (p = 0.002) AI at 3 and 2 cm showed a significantly change (p < 0.05 and p = 0.001, respectively). Ultrasound images demonstrated the presence of silicone in all sites of injection. Conclusion: In selected cases, trans-sphincteric silicone injection is an effective treatment for anal incontinence, as significant changes in quality of life and incontinence scales can be observed. The mechanism of action for which the studied agent improves anal incontinence seems to be related to improvement in the asymmetry index as well as a change in the HPZ.

Malgré le développement de biomatériaux de plus en plus nombreux dans le domaine des greffes osseuses et de la préservation alvéolaire, les résultats sont toujours insuffisants pour assurer des reconstructions ad integrum du tissu osseux. Les techniques d’ingénieries osseuses semblent être la piste à privilégier pour améliorer nos techniques chirurgicales. Le silicium poreux est un matériau prometteur pour l’ingénierie tissulaire et notamment pour la régénération osseuse. En effet, son état de surface permet une adhésion cellulaire importante et ses propriétés non toxique et résorbable en fond un matériau porteur de cellules souches intéressant. Les cellules souches de la pulpe dentaire (DPSC) sont des cellules facilement accessibles dans la cavité buccale. Leurs capacités de prolifération et de différenciation associées au silicium poreux semblent être un atout pour les applications thérapeutique pour la régénération osseuse. Des résultats d’études ultérieures in vitro ont montré leur fort intérêt à une application in vivo. Dans ce travail thèse, nous avons tester l’association silicium poreux et cellules souches de la pulpe dentaire, aux même caractéristiques énoncées dans l’étude de référence in vitro, chez l’animal. Pour cela, le matériau a été produit sous forme de particules de manière a être utilisé comme moyen de comblement osseux, associé ou non à des DPSC. Le modèle de queue de rat a été développé et tester pour diminuer le nombre d’animaux nécessaire à l’étude tout en conservant la puissance statistique des résultats. Les études ont montré la possibilité d’utiliser ce modèle pour la régénération de défauts osseux crées chirurgicalement. De plus, il semblerait que ce modèle puisse également être utile pour les études sur l’ostéointégration de système implantables et sur la régénération osseuse autour de ces implants. Le silicium poreux a ensuite été testé dans ces conditions, associé ou non aux DPSC, en comparaison avec un témoin positif et un témoin négatif. Cette association est apparue comme une piste prometteuse pour la régénération osseuse in vivo. / Despite the development of biomaterials in the field of bone grafts and alveolar preservation, the results are no sufficient to made reconstructions ad integrum of bone tissue. Bone engineering techniques seem to be the preferred way to improve our surgical techniques. Porous silicon is a promising material for tissue engineering and especially for bone regeneration. Indeed, its surface allows cell adhesion. And then, it’s a non-toxic and bioresorbable interesting material properties carrying stem cells. Dental pulp stem cells (DPSC) are easily accessible cells in the oral cavity. Their proliferation and differentiation capacities associated with porous silicon appear to be attractive for therapeutic applications in bone regeneration. The results of the in vitro studies have shown the interest for in vivo application. In this thesis, we have tested the combination of porous silicon and dental pulp stem cells in vivo experimentation, using the same characteristics of the in vitro reference study. For this, the material was produced in particle form to be used as bone filling material, associated or not with DPSC. The rat-tail model was developed and tested to reduce the number of animals needed for the study while maintaining the statistical power of the results. Studies have shown the possibility of using this model for bone regeneration defects surgically created. In addition, it seems that this model can also be useful for studies on osseointegration of implantable systems and bone regeneration around these implants. Then, the porous silicon was tested under these conditions, with or without DPSC, in comparison with a positive control and a negative control. This association has emerged as a promising approach for bone regeneration in vivo.