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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.

Poly(vinyl alcohol) hydrogel as a biocompatible viscoelastic mimetic for articular cartilage.

Britland, Stephen T., Eagland, D., Smith, Annie G., Twigg, Peter C., Grant, Colin A., Egan, A., Moody, A., Crowther, N.J. January 2006 (has links)
No / The prevalence of suboptimal outcome for surgical interventions in the treatment of full-thickness articular cartilage damage suggests that there is scope for a materials-based strategy to deliver a more durable repair. Given that the superficial layer of articular cartilage creates and sustains the tribological function of synovial joints, it is logical that candidate materials should have surface viscoelastic properties that mimic native articular cartilage. The present paper describes force spectroscopy analysis by nano-indentation to measure the elastic modulus of the surface of a novel poly(vinyl alcohol) hydrogel with therapeutic potential as a joint implant. More than 1 order of magnitude decrease in the elastic modulus was detected after adsorption of a hyaluronic acid layer onto the hydrogel, bringing it very close to previously reported values for articular cartilage. Covalent derivatization of the hydrogel surface with fibronectin facilitated the adhesion and growth of cultured rat tibial condyle chondrocytes as evidenced morphologically and by the observance of metachromatic staining with toluidine blue dye. The present results indicate that hydrogel materials with potential therapeutic benefit for injured and diseased joints can be engineered with surfaces with biomechanical properties similar to those of native tissue and are accepted as such by their constituent cell type.

The development of functional peptide scaffolds for cell culture

Szkolar, Laura January 2016 (has links)
Peptides and peptide derivatives have shown great scope as biomaterials and for biomedicaltherapy application. It has been demonstrated that classes of these peptides can form fibrillar hydrogels making them a good candidate for ECM mimics. In particular, the ionic complementary peptides, composed of alternating hydrophobic and hydrophilic amino acidshave been reported as successful cell scaffolds. The simple structure of such ionic complementary peptides is generally seen to spontaneously self-assemble into β-sheet richfibrils in the presence of water. The highly aqueous environment, along with the inter meshing of fibres, results in an architecture akin to the natural ECM of the body, making peptide hydrogels highly suitable as cell culture scaffolds. The structure of such hydrogels, usually comprising 8-32 amino acids, has been widely reported as easily modifiable, thus, allowing for control of the final material properties. This study explores the potential use of a range of ionic-complementary peptides for the culture of primary bovine chondrocytes. Modifications and additions to peptide sequence, such as charge and amino acid substitution, were investigated. In all studies only 1 design parameter (sequence, charge etc.) was varied, to allow for better understanding of the effect of materials properties upon cell response. The encapsulation of primary bovine chondrocytes was undertaken, with the aim of providing a suitable cell scaffold capable of maintaining chondrocyte viability and function in vitro. Despite in vivo work being beyond the scope of this thesis, the properties of the hydrogel scaffold were designed with final aim of being suitable for use with matrix associated autologous chondrocyte implantation (MACI) in clinical therapy.


January 2018 (has links)
acase@tulane.edu / Bringing a newly formulated drug used for neurological applications to the market is a highly time and labor-intensive process. The current pathway of bringing a drug to market requires extensive drug testing on animal models at the pre-clinical stage. Live animal models are expensive, low-throughput and increasingly recognized to be poor predictors of clinical outcomes in the process of drug development. An in vitro testing platform would address these above stated problems by providing a pre-screening process that could improve the high attrition rates of novel pharmaceutical compounds and also reduce the demand for the number of animals used for testing. This dissertation presents the progress of studies that were conducted to create a three-dimensional myelinated in vitro peripheral nerve-on-a-chip model that could be subject to electrophysiological and histological testing to be used as a tool for drug screening. In the first study, our model utilized an ultra-violet light cured methacrylated heparin hydrogel as the growth permissive substrate and a polyethylene glycol gel as a growth restrictive boundary that contained three-dimensional neural growth from an embryonic rat’s dorsal root ganglion explant. The model enabled electrophysiological field recording testing to measure metrics such as compound action potential amplitude and nerve conduction velocity. However, the heparin hydrogel presented issues with immunohistochemistry and histological studies leading us to recreate the model with a different growth permissive substrate. The second study utilized a methacrylated gelatin hydrogel in place of the heparin as the growth substrate. The dense neural growth was rapider than heparin while the gel allowed electrophysiological and histological testing to conclusively show the presence of myelin. Data from the histological testing was used to tabulate structural measurement such as percentage of myelinated axons and g-ratios which were then correlated with the electrophysiological data. This study paved way to use this model to simulate a demyelinating physiology and assess the effectiveness of a possible neuroprotective agent. The third and final study investigated the usage of the peripheral nerve-on-a-chip as model of demyelination by using forskolin and twitcher mouse serum, adapted from the established in vivo model of Krabbe’s disease. The effects of demyelination were observed using electrophysiological, immunohistochemistry, and histological studies. The corticosteroid dexamethasone was also included in the demyelination models to assess its extent of neuroprotection against the demyelinating agents. The results established a novel myelinated peripheral nerve-on-a-chip model which could be subject to electrophysiological, immunohistochemistry, and histological studies. The model has the potential to be used to simulate various pathologies and evaluate the efficacy of drugs before animal testing could be conducted. / 1 / Ashwin Sivakumar

A muscle mimetic polyelectrolyte–nanoclay organic–inorganic hybrid hydrogel: its self-healing, shape-memory and actuation properties

Banerjee, S.L., Swift, Thomas, Hoskins, Richard, Rimmer, Stephen, Singha, N.K. 17 January 2019 (has links)
yes / Here in, we describe a non-covalent (ionic interlocking and hydrogen bonding) strategy of self-healing in a covalently crosslinked organic-inorganic hybrid 15 nanocomposite hydrogel, with special emphasize on it's improved mechanical stability. The hydrogel was prepared via in-situ free radical polymerization of sodium acrylate (SA) and successive crosslinking in the presence of poly(2-(methacryloyloxy)ethyl trimethyl ammonium chloride) (PMTAC) grafted cationically armed starch and organically modified montmorillonite (OMMT). This hydrogel shows stimuli triggered self-healing following damage in both neutral and acidic solutions (pH=7.4 and pH=1.2). This was elucidated by tensile strength and rheological analyses of the hydrogel segments joined at their fractured points. Interestingly this hydrogel can show water based shape memory effects. It was observed that the ultimate tensile strength (UTS) of the self-healed hydrogel at pH = 7.4 was comparable to extensor digitorum longus (EDL) muscle of the New Zealand white rabbit. The as synthesized self-healable hydrogel was found to be non-cytotoxic against NIH 3T3 fibroblast cells. / Medical Research Council (MRC (MR/N501888/2))

Muscles artificiels à base d’hydrogel électroactif / Artificial muscle fabrication based on electroactive hydrogel

Bassil, Maria 15 September 2009 (has links)
Les hydrogels de Polyacrylamide (PAAM) hydrolysés sont des matériaux électroactifs biocompatibles non biodégradables. Ils possèdent des propriétés très proches de celles du muscle naturel et leur mode opérationnel basé sur la diffusion d’ions est similaire à celui existant dans les tissus musculaires naturels. Compte tenu de ces caractéristiques, ces hydrogels sont de bons candidats pour la conception de nouveaux muscles artificiels. Le problème qui limite leur utilisation réside dans leur temps de réponse qui reste encore inférieur à celui du système de fibres musculaires naturelles. Leur fonction actuatrice est limitée par le phénomène de diffusion en raison de leur structure massique qui est à l’origine de cycles de fonctionnement relativement lents. Dans le but de développer un nouveau système artificiel mimant le comportement du muscle squelettique naturel cette étude se divise en deux grandes étapes. La première étape vise le développement d’une étude de la synthèse de l’hydrogel de PAAM et de son mode de fonctionnement. Dans cette étude les effets des paramètres gouvernant la polymérisation sur les propriétés des hydrogels sont évalués. Les propriétés électrochimiques et le mécanisme d’activation des actuateurs soumis à une excitation électrique sont étudiés et le mode de fonctionnement des actuateurs est caractérisé et expliqué. La seconde étape est la proposition et le développement d’une nouvelle architecture de muscle artificiel à base de PAAM. Cette architecture consiste en une structure fibreuse du gel encapsulée par une couche en gel conducteur jouant le rôle d’électrodes. La structure fibreuse permet au système d’exhiber une réponse rapide et la couche en gel améliore ses propriétés mécaniques. Comme un premier pas dans la réalisation du modèle nous avons mis en place un nouveau procédé basé sur la technique d’électrofilage qui permet la génération de fibres linéairement disposées. En utilisant ce processus nous avons réussi à fabriquer des microfibres de PAAM réticulées, électroactives montrant des réponses rapides. / Hydrolyzed Polyacrylamide (PAAM) hydrogels are electroactive, biocompatible and non-biodegradable materials. Their main attractive characteristic is their operative similarity with biological muscles and particularly their life-like movement. They suit better the artificial muscle fabrication despite their response time which stays low compared to natural human muscle due to their bulky structure and due to the kinetics of the size dependence of their volume change. In order to copy the natural skeletal muscle design into a new artificial muscle system this study is divided into two steps. The first step is the development of a comprehensive study of the hydrogel itself in order to obtain the elementary background needed for the design of actuating devices based on this material. The effect of polymerization parameter on the hydrogel properties is investigated. The electrochemical properties and actuation mechanisms of the hydrogel is studied, the bending of PAAM actuators induced by electric field is discussed and a mechanism for the bending phenomenon is proposed. The second step is the proposition of a new artificial muscle architecture based on PAAM hydrogel. The model consists on a fiber like elements of hydrolyzed PAAM, working in parallel, embedded in a thin conducting gel layer which plays the role of electrodes. The fiber-like elements enable the system to exhibit relatively rapid response and the gel layers enhance their mechanical properties. Aiming to realize the model we have put in place a new electrospinning setup which is a modified process for the production of micro to nanofibers via electrostatic fiber spinning of polymer solutions. The main advantage of this technology is to produce aligned electrospun fibers over large areas by simple and a low cost process making it possible to produce fiberbased devices efficiently and economically. Using this setup, we succeeded in the fabrication of electroactive crosslinked hydrogel microfibers that can achieve fast electroactive response

Design of polysaccharide-based nanogels for the controlled release of insulin / Conception de nanogels à base de polysaccharides pour la libération contrôlée d'insuline

Poirot, Robin 21 December 2017 (has links)
La prise en charge du diabète de type I se fait à l’heure actuelle par des injections pluriquotidiennes d’insuline ou par l’utilisation d’une pompe à insuline qui va mimer l’activité pancréatique. Dans ce contexte, les nanogels sensibles au glucose représentent des candidats à fort potentiel pour une délivrance contrôlée de l’insuline.La majorité des matériaux développés à ce jour ne présentent pas d’études en vue d’application in vivo et ce, pour diverses raisons telles que la non validation du caractère biocompatible et biorésorbable de la matrice polymère. Afin de répondre à ces deux critères, nous avons choisi de développer des nanogels à base de polysaccharides biocompatibles et biodégradables.Des travaux antérieurs au sein du laboratoire ont porté sur la conception d’hydrogels à base d’acide hyaluronique. Le polysaccharide a été fonctionnalisé avec des dérivés de l’acide phénylboronique (PBA) et du maltose. Ces modifications permettent dans des conditions physiologiques de générer des réticulations boronate-ester. Ces liaisons permettent d’induire une modification de la structure des hydrogels en réponse à divers stimuli tel que le pH ou l’addition de composés saccharidiques.Afin de faciliter l’administration de tels matériaux, nous avons étendu ce concept à la formation de nanogels. Des nanogels sensibles au pH et/ou à l’addition de saccharides ont pu être obtenus en conditions physiologiques grâce au choix judicieux des polysaccharides partenaires modifiés par le PBA et des molécules portant des fonctions diol. Ces nanogels sont capables de piéger l’insuline lors de leur formation avec une efficacité d’encapsulation allant de 45% à 80% et une capacité d’encapsulation de 10% à 60%. Les premiers tests ont montré un faible relargage de l’insulin par nos nanogels.Finalement, au vue de la sensibilité au pH de nos nanogels et l’environnement acide présent autour des tumeurs, leur utilisation pour le traitement du cancer a été étudié. Des analyses in vitro ont démontré une faible toxicité de nos gels sur les cellules cancéreuses. Les premières expériences in vivo ont montré la capacité des nanogels à circuler dans le sang. / Type 1 diabetes management is currently done by multiple insulin injections or by the use of an insulin pump that will mimic pancreatic activity. In this context, glucose-sensitive nanogels represent high potential candidates for controlled delivery of insulin.The majority of materials developed so far are limited to biological in vitro studies, which is partly due to the non-biocompatibility and limited biodegradability of polymers used for the preparation of such materials. To fulfill these criteria, we proposed to develop nanogels based on biocompatible and biodegradable polysaccharides.Previous work in our laboratory focused on the design of boronate-crosslinked hydrogels based on hyaluronic acid. This polysaccharide was functionalized with derivatives of phenylboronic acid (PBA) and of maltose. The dynamic covalent boronate ester crosslinks between the polysaccharide chains enabled to induce a structural change of the hydrogel in response to various stimuli such as pH or addition of carbohydrate molecules.In order to facilitate administration of such materials, we extended the concept to the formation of nanogels. Sugar- and pH-sensitive nanogels could be successfully obtained in physiological conditions thanks to the judicious choice of the polysaccharide partners, bearing PBA moieties and diol-containing molecules.These nanogels can entrap insulin during their formation with an entrapment efficiency of 45% to 80% and a loading capacity ranging from 10% to 60%. Preliminary experiments indicated a low release of insulin from the nanogels.Finally, in view of the pH-sensitivity of these nanogels and the slight acidic pH of the tumor environment, we investigated their potential application for the treatment of cancer. In vitro experiment demonstrated a low toxicity of our nanogels on cancer cells. Preliminary in vivo experiments indicated that the nanogels can circulate in the bloodstream.

Conception et développement d’hydrogels pour l’ingénierie tissulaire appliquée au tissu osseux / Design and development of hydrogels for bone tissue engineering

Maisani, Mathieu 22 September 2017 (has links)
Le besoin clinique de nouvelles stratégies pour pallier les limites des techniques actuelles dans le cas de régénération osseuse a permis l’émergence de l’ingénierie tissulaire osseuse. Les stratégies basées sur les techniques d’ingénierie tissulaire semblent être une alternative à l’utilisation de greffes et ainsi de s’affranchir des limites qu’elles présentent. L’approche adoptée dans le cadre de cette thèse consiste en le développement et l’utilisation d’hydrogels comme matériaux d’échafaudage pour le comblement et la régénération de tissus osseux. De nombreuses approches utilisant elles aussi des hydrogels existent, chacune possède ses avantages et limites. Dans ce contexte, nos travaux ont consisté en l’utilisation d’un hydrogel non-polymérique comme matériau de base dans le développement des stratégies. Brièvement, plusieurs types cellulaires sont présents au sein du tissu osseux et vont participer aux processus de formation et de régénération osseuse. L’objectif de nos stratégies a été l’apport de cellules souches exogènes puis leur différenciation en cellules ostéoformatrices, ou le recrutement et la différenciation des cellules de l’hôte en cellules ostéoformatrices. Le gel de GNF a été utilisé comme matrice tridimensionnelle pour ses propriétés d’injectabilité, de gélification en l’absence d’agent de réticulation toxique et son potentiel ostéoinducteur. Ce travail a consisté au développement de stratégies pour l’ingénierie tissulaire osseuse en associant le gel de GNF à une matrice naturelle de collagène cellularisée ou à des molécules bioactives pour promouvoir la régénération de lésions osseuses. Ces travaux ont permis de développer et caractériser des stratégies pertinentes pour la régénération de lésions osseuses basées sur l’utilisation d’hydrogels. / New strategies to overcome the clinical limitations of current techniques for bone defect filling and regeneration has led to the involvement of bone tissue engineering. Indeed, strategies based on tissue engineering techniques seem to be an alternative to the use of grafts and thus to defeat their limits. The approach employed in this thesis consists in development and use of hydrogels as scaffold materials for bone defect filling and regeneration. There are many approaches that also use hydrogels, each one with its advantages and limitations. In this context, our work consisted in the use of a non-polymeric hydrogel as basic material in the development of strategies for bone tissue engineering. Briefly, several cell types are present within bone tissue and will participate in the processes of bone formation and regeneration. The objective of our strategies was the contribution of exogenous stem cells and then their differentiation into osteogenic cells or the recruitment and differentiation of the host cells into osteogenic cells within the material. The GNF gel was used as a three-dimensional matrix considering its properties of injectability, gelation in the absence of toxic crosslinking agent and its osteoinductive potential. The goal was to develop strategies for bone tissue engineering by combining the GNF gel with a natural matrix of cellular collagen or bioactive molecules to promote the regeneration of bone lesions. This work allowed to develop and characterize strategies relevant to the regeneration of bone lesions based on the use of hydrogels.

Degradable poly(ethylene glycol) based hydrogels for pulmonary drug delivery and in vitro T cell differentiation applications

Fleury, Asha Tarika 08 October 2013 (has links)
Hydrogels, defined as three-dimensional, hydrophilic networks, offer extensive biomedical applications. The areas of application are heavily concentrated in drug delivery and tissue engineering because of the hydrogels’ ability to mimic extracellular matrixes of tissue while maintaining a high level of biocompatibility. Specifically, poly(ethylene glycol) (PEG) is a well-established biomaterial in hydrogel applications due to its high water-solubility, low toxicity, high biocompatibility, and stealth properties. This thesis discusses two applications of PEG-based degradable hydrogels. The first is the targeted, site-specific, controlled release of biologic drugs administered by inhalation. There are many challenges to designing a pulmonary delivery system for inhalation of biologic drugs such as low respirable fractions and short resident time in the lungs. In this report, the hydrogel microcarriers for encapsulated drugs were formed by cross-linked PEG and peptide sequences synthesized during a mild emulsion process. The microgels underwent freeze-drying in the presence of cryoprotectants and formulated for dry powder inhalation. The microgels displayed swelling properties to avoid local macrophage clearance in the lungs and exhibited triggered release and degradation in response to enzyme for disease specific release. Dry formulations were tested for aerosolization properties and indicated ability to be delivered to the deep lung by a dry powder inhaler. Lastly, microgels were successfully delivered to mice lungs via intratracheal aerosol delivery. This thesis also discusses the use of PEG-based hydrogel as a biomaterial microenvironment for encapsulated stem cells as a means of in vitro T cell differentiation. A 3D hydrogel system creates a biomimetic reconstruction of the cell’s natural microenvironment and allows us to adjust factors such as ligand density and mechanical properties of the hydrogel in order to promote cells differentiation. This report utilizes hydrogels of cross-linked hyaluronic acid and PEG to encapsulate mice bone marrow hematopoietic progenitor cells in the presence of notch ligands, displayed through stromal cells, magnetic microbeads, or immobilized within the hydrogel matrix. Mechanical properties of the hydrogels were tested and the release of encapsulated cells was performed by enzymatic degradation or dissolution. The differentiation data obtained indicated successful differentiation of stem cells into early T cells through the hydrogel system. / text

Über die Denaturierungstemperatur des Enzyms Glukoseoxidase als Mass seiner Funktionsstabilität sowie ihre nano-kalorimetrische Bestimmung

Weiß, Thomas. January 2006 (has links)
Freiburg i. Br., Univ., Diss., 2007.

Nano-structured temperature sensitive hydrogels crosslinked by high energy radiation

Schmidt, Thomas January 2005 (has links)
Zugl.: Dresden, Techn. Univ., Diss., 2005

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