<p>Includes Bibliographical references (leaves 83- 94).Forty-three male athymic nude mice were implanted with human vaginal mucosal cysts under general anaesthesia with Ketamine [25mg/kg] and Medetomidine [0.5mg/kg]. Cysts in 37 mice were recovered after 9 weeks of growth. twenty three cyst linings had retained the original structure of the vaginal epithelium. No marked deifference was present between the thickness of 9 week old linings and donor vaginal epithelium. The contaminants isolated from the skin of mice before implantation were mainly normal commercals of healthy experimental animals. There was no distinct difference in the number of cases with intact cyst formation between the terramycin/vitamin cocktaik group. The frequency of poor wound healing and/ or murine epidermis ingrowth was three times higher in animals stitched with silk sutures that in those cases where nylon sutures were used.</p>

<p>Includes Bibliographical references (leaves 83- 94).Forty-three male athymic nude mice were implanted with human vaginal mucosal cysts under general anaesthesia with Ketamine [25mg/kg] and Medetomidine [0.5mg/kg]. Cysts in 37 mice were recovered after 9 weeks of growth. twenty three cyst linings had retained the original structure of the vaginal epithelium. No marked deifference was present between the thickness of 9 week old linings and donor vaginal epithelium. The contaminants isolated from the skin of mice before implantation were mainly normal commercals of healthy experimental animals. There was no distinct difference in the number of cases with intact cyst formation between the terramycin/vitamin cocktaik group. The frequency of poor wound healing and/ or murine epidermis ingrowth was three times higher in animals stitched with silk sutures that in those cases where nylon sutures were used.</p>

Magister Scientiae Dentium - MSc(Dent) / Includes Bibliographical references (leaves 83- 94).Forty-three male athymic nude mice were implanted with human vaginal mucosal cysts under general anaesthesia with Ketamine [25mg/kg] and Medetomidine [0.5mg/kg]. Cysts in 37 mice were recovered after 9 weeks of growth. twenty three cyst linings had retained the original structure of the vaginal epithelium. No marked deifference was present between the thickness of 9 week old linings and donor vaginal epithelium. The contaminants isolated from the skin of mice before implantation were mainly normal commercals of healthy experimental animals. There was no distinct difference in the number of cases with intact cyst formation between the terramycin/vitamin cocktaik group. The frequency of poor wound healing and/ or murine epidermis ingrowth was three times higher in animals stitched with silk sutures that in those cases where nylon sutures were used. / South Africa

Thesis (Ph.D)--Biomedical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Bellamkonda, Ravi; Committee Member: Babensee, Julia; Committee Member: Butera, Robert; Committee Member: DeWeerth, Steve; Committee Member: Lee, Robert; Committee Member: McKeon, Robert. Part of the SMARTech Electronic Thesis and Dissertation Collection.

<p>The success of implanted medical devices, such as biosensors, is dependent on the immune reaction to the surface of the implanted material. This immune reaction, termed the foreign body reaction, is potentially affected by the physical and chemical properties of the implanted material. Macrophages interact with the surface of the implanted material and secrete intercellular signals, including cytokines and growth factors, which direct the actions of immune cells in the surrounding tissue. The type and quantity of cytokines and growth factors produced by macrophages at an implant surface could be an indicator of the outcome of the foreign body reaction. </p><p>This study investigated the effect of the surface chemistry of an implanted device on the production of cytokines and growth factors. First, microdialysis sampling was characterized as a technique for collecting cytokines and growth factors from the tissue surrounding an implant. Based on this characterization, it was determined that a direct sampling method would be more suitable than microdialysis sampling for determining accurate tissue concentrations of cytokines and growth factors. Second, an in vitro model was developed and utilized to assess cytokine and growth factor production from monocyte/macrophage cultures seeded onto commonly implanted polymeric biomaterials with varying surface chemistries. The materials included in this study were polyethylene (PE), polyurethane (PU), polymethyl methacrylate (PMMA), expanded polytetrafluoroethylene (ePTFE), and a cytotoxic organo-tin polyvinyl chloride (ot-PVC) as a positive control. From this in vitro model, it was determined that the varying surface chemistries of these non-toxic materials, excluding ot-PVC, did not significantly affect the types and quantities of cytokines and growth factors produced. Finally, an in vivo model for evaluating the cytokine and growth factor response to an implanted biomaterial was utilized for comparison with the in vitro findings. In this model, biomaterials were implanted subcutaneously within the lumen of a stainless steel mesh cage. The mesh cage served to create a "pocket" where wound exudate fluid collected within the cage, surrounding the implanted biomaterial. The materials included in this study were PE, PU, and ot-PVC. Cytokines and growth factors produced at the material surface were sampled directly from the exudate fluid. The results from this in vivo study indicate that cytokine and growth factor production were not significantly impacted by the varying surface chemistries of the implanted biomaterials. The in vivo data support the findings from the in vitro model, suggesting that the foreign body reaction proceeds in a similar fashion for each of these non-cytotoxic, polymeric biomaterials with varying surface chemistries.</p> / Dissertation

Les biopiles enzymatiques miniatures représentent un potentiel important pour la future génération de dispositifs médicaux implantables, utilisés pour le diagnostic, le pronostic et le traitement. Ces derniers fonctionnent actuellement avec des sources d'énergie externes. Ces biopiles utilisant les molécules présentes dans les fluides biologiques sont des dispositifs médicaux prometteurs. Le glucose, qui est abondamment disponible dans le corps, est à l’étude comme biocarburant permettant de produire de l’énergie. Les enzymes utilisées pour produire l'énergie à partir des produits biochimiques sont immobilisées sur des électrodes en or par des médiateurs redox. Cependant, la faible puissance actuellement disponible et la sensibilité des enzymes à l'environnement limitent leur application in vivo. Malgré des recherches intensives, de nombreux problèmes restent à résoudre, notamment l'amélioration de la puissance, de la stabilité et de la biocompatibilité des biopiles.La réaction à corps étranger et l'isolement du dispositif médical par la formation d'une capsule fibreuse peuvent d'une part dénaturer les enzymes et, d'autre part, entraver la diffusion des analytes et de l'oxygène. Le travail décrit dans cette thèse vise à protéger les biopiles fonctionnant à base de glucose. Afin de résoudre les problèmes mentionnés ci-dessus, les hydrogels, actuellement développés pour diverses applications telles que l'administration de médicaments, l'ingénierie tissulaire et les dispositifs médicaux, offrent des propriétés prometteuses en tant que matériaux de revêtement.La première partie de la thèse est centrée sur l'évaluation de différents hydrogels injectables de faible poids moléculaire, en analysant à la fois la gélification in vitro et in vivo, la cinétique de dégradation, la réaction à corps étranger et l'angiogenèse. Les hydrogels présentent une dégradation lente et une intégration tissulaire optimale. Une angiogenèse accrue a été observée en raison de la libération d'une molécule pro-angiogénique pendant la dégradation de l'hydrogel.Dans la seconde partie de la thèse, l'un des hydrogels étudiés a été utilisé pour recouvrir l'électrode en or : le choix de l'enzyme a été basé sur des études de stabilité in vitro. En parallèle, le processus de revêtement a été optimisé, à la fois pour son uniformité et son épaisseur. Même si un revêtement plus épais présente l’avantage de protéger l’électrode contre la réaction à corps étranger, il est nécessaire de limiter l’épaisseur afin de maintenir une diffusion efficace des analytes et de l’oxygène.Les expériences en cours décrites dans la dernière partie de la thèse sont axées sur l'optimisation de l'implantation chez le rat et la mesure de l'activité des biopiles. De plus, les électrodes ont été connectées à une antenne pour établir une communication sans fil ; en effet, cela permettrait une mesure non invasive de l'activité enzymatique.En conclusion, ces travaux ont permis d'identifier un hydrogel pouvant être utilisé pour revêtir les électrodes de biopiles. Le sous-produit libéré lors de la biodégradation favorise l'angiogenèse au voisinage du matériau. Grâce à ce revêtement, on peut donc s'attendre à un échange accru d'analytes et d'oxygène, préalable indispensable à l'activité enzymatique. / Miniature enzymatic biofuel cells hold great potential to power the future generation of implantable medical devices, which are currently working on external power sources used for diagnosis, prognosis and treatment. Enzymatic biofuel cells appear to be promising in harvesting the energy from biochemicals present in physiological body fluids. Glucose, which is abundantly available in the body, is being explored as a biofuel to harvest energy. The enzymes employed to harvest the energy from the biochemicals are electrically wired on gold electrodes by redox mediators. However, the limitation of insufficient power, and the sensitivity of the enzymes towards host environment restrict their in vivo application. Despite several attempts, numerous challenges remain to be addressed such as improved current density, increased stability, and biocompatibility of enzymatic biofuel cells.Foreign body reaction and isolation of the medical device by formation of a fibrous capsule may firstly denature the enzymes, and secondly hinder the diffusion of analytes and oxygen. The work described in this thesis aims at protecting glucose based biofuel cells. As a strategy for combatting the bottlenecks mentioned above, hydrogels, currently developed for various applications such as drug delivery, tissue engineering, and medical device, offer promising properties as coating materials.The first part of the thesis is focused on evaluating different low molecular weight injectable hydrogels by analysing both in vitro and in vivo gel formation, degradation kinetics, foreign body reaction and angiogenesis. The hydrogels exhibit slow degradation, and optimal tissue integration. Enhanced angiogenesis was observed due to a pro-angiogenic molecule released during hydrogel degradation.In the second part of the thesis, one of the studied hydrogels was used to coat the gold electrode functionalised with enzyme: the selection of the enzyme was based on in vitro stability studies. In parallel, the process of coating was optimised, both for uniformity and thickness. Although a thicker coating should protect the electrode against foreign body reaction, it was necessary to limit the thickness in order to maintain an efficient analyte and oxygen diffusion.Ongoing experiments described in the last part of the thesis are focused on the optimisation of implantation in rat and measurement of the biofuel cell activity. In addition, the electrodes were connected to an antenna for wireless communication; indeed, such a device would allow for a non-invasive measurement of enzyme activity.To conclude, this work allowed for the identification of a hydrogel that can be used to coat the electrodes of biofuel cells. The byproduct released during the biodegradation favours angiogenesis in the vicinity of the material. Thanks to this coating, we can therefore expect an enhanced exchange of analytes and oxygen, which is a prerequisite for enzyme activity.

Thesis (118-130)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 118-130).

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 113-116).

No description available.

The dermal filler Sculptra® has been employed to treat facial volume loss and age-related wrinkles in Europe since 1999. Sculptra® injections were administered 87,946 times (increase of 25.7% to 2012) in the USA in 2013. Except for histological analysis and clinical reports, data based on molecular biology or biochemistry, enlightening the mechanisms of action, do not exist to date. In contrast, such data are available for cross-linked hyaluronic acid, which is also administered for facial augmentation. To overcome this gap of knowledge, a comprehensive study about macroscopic to microscopic events occurring after Sculptra® injections was conducted. The augmentation of facial tissue with Sculptra® is approved; however, as the required repetitive biopsies could not be taken from the face, Sculptra® was injected to the inner side of the upper arms of 21 volunteers. Furthermore, this “off label use” was documented: The effect of the injections on the volunteer’s subjective quality of life was investigated using a questionnaire. For objective evaluation, the upper arms were photographed and sonographic measurements were applied. Photos of the treated upper arms revealed no changes in their shape during the study course. The amount of Sculptra® administered was not sufficient to augment the upper arms of postmenopausal women. Furthermore, these applied Sculptra® treatments of the upper arm did not improve the volunteers’ quality of life significantly. Upon sonographic measurement, however, a highly significant decrease in echogenicity was retrieved by comparing baseline subepidermal tissue values (t0) with 20 month (t2) values from either arm. Upon comparison of both treated sides, echogenicity was comparable; therefore 22 MHz sonography is an objective non-invasive measure to document the subcutaneous effect of Sculptra®. Immunofluorescence staining of sections from biopsies characterised the cell infiltrate and collagen type. CD68+ macrophages were found in direct proximity to PLLA, CD90+ fibroblasts aligned adjacently, while αSMA positive structures indicated myofibroblasts and neovascularisation. Substantial collagen type III deposition was detected right next to PLLA particles and collagen type I in the periphery of a given PLLA encapsulation. mRNA expression was strongly up-regulated for collagen type I and III transcripts, as well as for TGFß1 and TIMP1. PLLA particles were still retrievable 28 months after subcutaneous application. The augmenting effect of Sculptra® is generated by a complex reaction, comprised of various cells, chemokines and cytokines, leading to the proliferation of fibroblasts and their differentiation into myofibroblasts, synthesising a substantial amount of collagen in order to restore subcutaneous volume deficiencies. Degradation of facial and extra facial PLLA particles is considerably slower than described previously. The augmenting effect of Sculptra® diminishes over a period of 18-20 months in the face, but the degradation of PLLA particles seems to be much slower. Whether Sculptra® stimulates the synthesis of other ECM components, such as HA, or rationalises a continuous stimulus for collagen production, at least as long as it is not synthesised, should be analysed in further studies.