Academic literature on the topic 'Tissue-on-chip'
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Journal articles on the topic "Tissue-on-chip"
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Narciso, Cody, Kyle R. Cowdrick, Victoria Zellmer, Teresa Brito-Robinson, Pavel Brodskiy, David J. Hoelzle, Siyuan Zhang, and Jeremiah J. Zartman. "On-chip three-dimensional tissue histology for microbiopsies." Biomicrofluidics 10, no. 2 (March 2016): 021101. http://dx.doi.org/10.1063/1.4941708.
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Dorrigiv, Dina, Kayla Simeone, Laudine Communal, Jennifer Kendall-Dupont, Amélie St-Georges-Robillard, Benjamin Péant, Euridice Carmona, Anne-Marie Mes-Masson, and Thomas Gervais. "Microdissected Tissue vs Tissue Slices—A Comparative Study of Tumor Explant Models Cultured On-Chip and Off-Chip." Cancers 13, no. 16 (August 21, 2021): 4208. http://dx.doi.org/10.3390/cancers13164208.
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Predicting patient responses to anticancer drugs is a major challenge both at the drug development stage and during cancer treatment. Tumor explant culture platforms (TECPs) preserve the native tissue architecture and are well-suited for drug response assays. However, tissue longevity in these models is relatively low. Several methodologies have been developed to address this issue, although no study has compared their efficacy in a controlled fashion. We investigated the effect of two variables in TECPs, specifically, the tissue size and culture vessel on tissue survival using micro-dissected tumor tissue (MDT) and tissue slices which were cultured in microfluidic chips and plastic well plates. Tumor models were produced from ovarian and prostate cancer cell line xenografts and were matched in terms of the specimen, total volume of tissue, and respective volume of medium in each culture system. We examined morphology, viability, and hypoxia in the various tumor models. Our observations suggest that the viability and proliferative capacity of MDTs were not affected during the time course of the experiments. In contrast, tissue slices had reduced proliferation and showed increased cell death and hypoxia under both culture conditions. Tissue slices cultured in microfluidic devices had a lower degree of hypoxia compared to those in 96-well plates. Globally, our results show that tissue slices have lower survival rates compared to MDTs due to inherent diffusion limitations, and that microfluidic devices may decrease hypoxia in tumor models.
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Tavakol, Daniel Naveed, Sharon Fleischer, and Gordana Vunjak-Novakovic. "Harnessing organs-on-a-chip to model tissue regeneration." Cell Stem Cell 28, no. 6 (June 2021): 993–1015. http://dx.doi.org/10.1016/j.stem.2021.05.008.
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Authasing, S., S. Chantanetra, S.Mitatha, and P. P. Yupapin. "Tissue Culture On-chip Design using Multivariable Molecular Network." Procedia Engineering 32 (2012): 286–90. http://dx.doi.org/10.1016/j.proeng.2012.01.1269.
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WANG, Wei-Xin, Wei-Ping LIU, Bin WU, Guang-Tie LIANG, and Da-Yu LIU. "Construction of Tumor Tissue Microarray on a Microfluidic Chip." Chinese Journal of Analytical Chemistry 43, no. 5 (May 2015): 637–42. http://dx.doi.org/10.1016/s1872-2040(15)60823-4.
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Haim, Yulia, Tanya Tarnovscki, Dana Bashari, and Assaf Rudich. "A chromatin immunoprecipitation (ChIP) protocol for use in whole human adipose tissue." American Journal of Physiology-Endocrinology and Metabolism 305, no. 9 (November 1, 2013): E1172—E1177. http://dx.doi.org/10.1152/ajpendo.00598.2012.
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Chromatin immunoprecipitation (ChIP) has become a central method when studying in vivo protein-DNA interactions, with the major challenge being the hope to capture “authentic” interactions. While ChIP protocols have been optimized for use with specific cell types and tissues including adipose tissue-derived cells, a working ChIP protocol addressing the challenges imposed by fresh whole human adipose tissue has not been described. Utilizing human paired omental and subcutaneous adipose tissue obtained during elective abdominal surgeries, we have carefully identified and optimized individual steps in the ChIP protocol employed directly on fresh tissue fragments. We describe a complete working protocol for using ChIP on whole adipose tissue fragments. Specific steps required adaptation of the ChIP protocol to human whole adipose tissue. In particular, a cross-linking step was performed directly on fresh small tissue fragments. Nuclei were isolated before releasing chromatin, allowing better management of fat content; a sonication protocol to obtain fragmented chromatin was optimized. We also demonstrate the high sensitivity of immunoprecipitated chromatin from adipose tissue to freezing. In conclusion, we describe the development of a ChIP protocol optimized for use in studying whole human adipose tissue, providing solutions for the unique challenges imposed by this tissue. Unraveling protein-DNA interaction in whole human adipose tissue will likely contribute to elucidating molecular pathways contributing to common human diseases such as obesity and type 2 diabetes.
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Nitsche, Katharina S., Iris Müller, Sophie Malcomber, Paul L. Carmichael, and Hans Bouwmeester. "Implementing organ-on-chip in a next-generation risk assessment of chemicals: a review." Archives of Toxicology 96, no. 3 (February 1, 2022): 711–41. http://dx.doi.org/10.1007/s00204-022-03234-0.
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AbstractOrgan-on-chip (OoC) technology is full of engineering and biological challenges, but it has the potential to revolutionize the Next-Generation Risk Assessment of novel ingredients for consumer products and chemicals. A successful incorporation of OoC technology into the Next-Generation Risk Assessment toolbox depends on the robustness of the microfluidic devices and the organ tissue models used. Recent advances in standardized device manufacturing, organ tissue cultivation and growth protocols offer the ability to bridge the gaps towards the implementation of organ-on-chip technology. Next-Generation Risk Assessment is an exposure-led and hypothesis-driven tiered approach to risk assessment using detailed human exposure information and the application of appropriate new (non-animal) toxicological testing approaches. Organ-on-chip presents a promising in vitro approach by combining human cell culturing with dynamic microfluidics to improve physiological emulation. Here, we critically review commercial organ-on-chip devices, as well as recent tissue culture model studies of the skin, intestinal barrier and liver as the main metabolic organ to be used on-chip for Next-Generation Risk Assessment. Finally, microfluidically linked tissue combinations such as skin–liver and intestine–liver in organ-on-chip devices are reviewed as they form a relevant aspect for advancing toxicokinetic and toxicodynamic studies. We point to recent achievements and challenges to overcome, to advance non-animal, human-relevant safety studies.
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Moradi, Ehsanollah, Sasan Jalili-Firoozinezhad, and Mehran Solati-Hashjin. "Microfluidic organ-on-a-chip models of human liver tissue." Acta Biomaterialia 116 (October 2020): 67–83. http://dx.doi.org/10.1016/j.actbio.2020.08.041.
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Zoio, Patrícia, Sara Lopes-Ventura, and Abel Oliva. "Barrier-on-a-Chip with a Modular Architecture and Integrated Sensors for Real-Time Measurement of Biological Barrier Function." Micromachines 12, no. 7 (July 12, 2021): 816. http://dx.doi.org/10.3390/mi12070816.
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Biological barriers are essential for the maintenance of organ homeostasis and their dysfunction is responsible for many prevalent diseases. Advanced in vitro models of biological barriers have been developed through the combination of 3D cell culture techniques and organ-on-chip (OoC) technology. However, real-time monitoring of tissue function inside the OoC devices has been challenging, with most approaches relying on off-chip analysis and imaging techniques. In this study, we designed and fabricated a low-cost barrier-on-chip (BoC) device with integrated electrodes for the development and real-time monitoring of biological barriers. The integrated electrodes were used to measure transepithelial electrical resistance (TEER) during tissue culture, thereby quantitatively evaluating tissue barrier function. A finite element analysis was performed to study the sensitivity of the integrated electrodes and to compare them with conventional systems. As proof-of-concept, a full-thickness human skin model (FTSm) was grown on the developed BoC, and TEER was measured on-chip during the culture. After 14 days of culture, the barrier tissue was challenged with a benchmark irritant and its impact was evaluated on-chip through TEER measurements. The developed BoC with an integrated sensing capability represents a promising tool for real-time assessment of barrier function in the context of drug testing and disease modelling.
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Sateesh, Jasti, Koushik Guha, Arindam Dutta, Pratim Sengupta, Dhanya Yalamanchili, Nanda Sai Donepudi, M. Surya Manoj, and Sk Shahrukh Sohail. "A comprehensive review on advancements in tissue engineering and microfluidics toward kidney-on-chip." Biomicrofluidics 16, no. 4 (July 2022): 041501. http://dx.doi.org/10.1063/5.0087852.
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This review provides a detailed literature survey on microfluidics and its road map toward kidney-on-chip technology. The whole review has been tailored with a clear description of crucial milestones in regenerative medicine, such as bioengineering, tissue engineering, microfluidics, microfluidic applications in biomedical engineering, capabilities of microfluidics in biomimetics, organ-on-chip, kidney-on-chip for disease modeling, drug toxicity, and implantable devices. This paper also presents future scope for research in the bio-microfluidics domain and biomimetics domain.
Dissertations / Theses on the topic "Tissue-on-chip"
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Rathbone, Daniel Rodion. "A low volume oxygenator for open well Liver-on-a-Chip tissue culture." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/120193.
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Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2018.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 139-142).
MicroPhysiological Systems (MPS) show significant promise in speeding drug development and advancing basic research. They may serve better than animal models for obtaining accurate human response data and thereby reducing failed clinical trials. The CN Bio LiverChip is one such commercial MPS device which cultures liver cells on a perforated polystyrene scaffold and actively circulates cell culture medium through them. Reducing the total circulating volume is desirable to increase the concentration of difficult-to-detect compounds, improve autocrine signaling, and achieve more physiologically relevant drug decay times. However, achieving adequate oxygenation at lower volumes is challenging due to surface tension effects. This thesis describes an open-well, flow-through MPS platform with a low-volume oxygenator, at a total circulating volume of approximately 500 [mu]L. The oxygenator uses the interior corner of a hydrophilic spiral to constrain the circulating fluid and to create a thin fluid region, which decreases the diffusion depth relative to exposed surface area, thereby improving oxygenation. The oxygenator performs equivalently to the LiverChip at a fraction of the volume, and features a downward slope that prevents fluid from accumulating in the oxygenator, which could deplete the cell culture well. The fluidic configuration and other design considerations are described, as well as hardware testing results and improved methods for preventing fluid from bypassing the scaffold. This project was supported by NIH grant number UH3-TR000496.
by Daniel Rodion Rathbone.
S.M.
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Minier, Nicolas. "Development of an organ-on-chip microfluidic device incorporating an actuatable hydrogel layer to produce barrier tissue mimicries on chips." Thesis, Compiègne, 2021. https://bibliotheque.utc.fr/Default/doc/SYRACUSE/2021COMP2644.
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Alors que l’éthique et la loi poussent la recherche à plus de sécurité, ainsi qu’à une moindre utilisation des animaux, il est devenu crucial de développer des systèmes in vitro d’une plus grande pertinence. Depuis la fin du XXe siècle, plusieurs systèmes ont fait leur apparition pour tenter de pallier les difficultés rencontrées, et notamment les « organes-sur-puces » (organ-on-chip systems). Ces systèmes microfluidiques de culture cellulaire avancés permettant de recréer certaines fonctions tissulaires grâce au contrôle très précis des conditions du microenvironnement cellulaire. Malgré les avancées de la bioingénierie et l’amélioration de nos méthodes de culture in vitro, la discipline est jeune et de nombreux progrès restent à faire. Les travaux présentés ici détaillent le développement d’un organe-sur-puce incluant une membrane d'hydrogel déformable et dégradable, aux propriétés physico-chimiques proches de tissus mous tels que les poumons ou les intestins. Cette puce semble pertinente pour accueillir des tissus barrières, composés de plusieurs types cellulaires, organisés de part et d'autre, ainsi qu'au sein de cette barrière, souvent soumise à des stimuli mécaniques. Durant ce doctorat, plusieurs objectifs ont été atteints : - Concevoir et fabriquer un organe-sur-puce incluant un hydrogel biocompatible et déformable, ainsi qu’un système microfluidique permettant le contrôle indépendant du flux et de la déformation de la membrane d’hydrogel. - Caractériser la déformation subie par l’hydrogel. - Cultiver dans la puce des cellules intestinales, formant un épithélium structuré en trois dimensions, et caractériser sa perméabilité à des molécules de tailles variéesModern day ethics and laws call for more safety and use of fewer animals in biomedical research. It became crucial to develop novel in vitro devices of higher relevance. Since the end of the twentieth century, several systems have been proposed by researchers in attempts to palliate the shortcomings of current systems. Notably, organs-on-chip systems are specifically tailored to recapitulate tissue functions in a manner that remains easily accessible for the experimenter. Despite the significant improvements that were brought during the last century to in vitro cell and tissue culture systems, the field of bioengineering is still young and much progress remains to be done. The work presented here details the development of an organ-on-chip that includes a biocompatible and actuatable hydrogel membrane, with controlled physico-chemical properties. Such chip is relevant when hosting barrier tissues, which are composed of several cell types, disposed on each side of a barrier, as well as within its bulk, and are often submitted to mechanical stimuli. During this PhD, several objectives have been attained. Notably, we: - Designed and produced an organ-on-chip including a biocompatible and actuatable hydrogel layer, as well as a microfluidic system allowing the independent control of both flow and actuation. - Characterized the deformation of the hydrogel layer. - Cultured intestinal cells within the chip, which formed a three dimensionally structure epithelium, and characterized its apparent permeability to molecules of varying sizes
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Sivaraman, Anand 1977. "A microfabricated 3D tissue engineered "Liver on a Chip" : information content assays for in vitro drug metabolism studies." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/28661.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2004.Includes bibliographical references (p. 180-195).
(cont.) approaches to improving hepatocyte function in culture have been described, not all of the important functions--specifically the biotransformation functions of the liver--can as yet be replicated at desired in ivo levels, especially in culture formats amenable to routine use in drug development. The in vivo microenvironment of hepatocytes in the liver capillary bed includes signaling mechanisms mediated by cell-cell and cell-matrix interactions, soluble factors, and mechanical forces. This thesis focuses on the design, fabrication, modeling and characterization of a microfabricated bioreactor system that attempts to mimic the in vivo microenvironment by allowing for the three dimensional morphogenesis of liver tissue under continuous perfusion conditions. A key feature of the bioreactor that was designed is the distribution of cells into many tiny ([approximately]0.001 cm³) tissue units that are uniformly perfused with culture medium. The total mass of tissue in the system is readily adjusted for applications requiring only a few thousand cells to those requiring over a million cells by keeping the microenvironment the same and scaling the total number of tissue units in the reactor. Using a computational fluid dynamic model in ADINA® and a species conservation mass transfer model in FEMLAB®, the design of the bioreactor and the fluidic circuit was optimized to mimic physiological shear stress rates ...
Recent reports indicate that it takes nearly $800 million dollars and 10-15 years of development time to bring a drug to market. The pre-clinical stage of the drug development process includes a panel of screens with in vitro models followed by comprehensive studies in animals to make quantitative and qualitative predictions of the main pharmacodynamic, pharmacokinetic, and toxicological properties of the candidate drug. Nearly 90% of the lead candidates identified by current in vitro screens fail to become drugs. Among lead compounds that progress to Phase I clinical trials, more than 50% fail due to unforeseen human liver toxicity and bioavailability issues. Clearly, better methods are needed to predict human responses to drugs. The liver is the most important site of drug metabolism and a variety of ex vivo and in vitro model systems have therefore been developed to mimic key aspects of the in vivo biotransformation pathways of human liver-- a pre-requisite for a good, predictive pharmacologically relevant screen. Drug metabolism or biotransformation in the liver involves a set of Phase I (or p450 mediated) and Phase II enzyme reactions that affect the overall therapeutic and toxic profile of a drug. The liver is also a key site of drug toxicity following biotransformation, a response that is desirable but difficult to mimic in vitro. A major barrier to predictive liver metabolism and toxicology is the rapid (hours) loss of liver-specific functions in isolated hepatocytes when maintained under standard in itrom cell culture condition. This loss of function may be especially important in predicting toxicology, where the time scale for toxic response may greatly exceed the time scale for loss of hepatocyte function in culture. Although a wide variety of
by Anand Sivaraman.
Ph.D.
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Boulais, Lilandra. "Cryogel-integrated hepatic cell culture microchips for liver tissue engineering." Thesis, Compiègne, 2020. http://www.theses.fr/2020COMP2561.
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L’un des enjeux de l’industrie pharmaceutique aujourd’hui est de développer des modèles de foie in vitro fidèles pour améliorer la prédictivité des études précliniques, notamment l’étude de la toxicité et de l’efficacité des médicaments candidats. Ces dernières années, l’ingénierie tissulaire, approche multidisciplinaire pour développer des tissus, a mené au développement de nouvelles méthodes de culture cellulaire. Parmi elles, les cultures de cellules en 3D ou en perfusion ont permis d’obtenir des activités hépatiques similaires à celles observées in vivo. L’objectif de cette thèse est de combiner ces deux méthodes de culture cellulaire pour créer un modèle de foie in vitro encore plus fidèle. Pour cela, nous cherchons à développer un cryogel d’alginate intégré en micropuce avec des propriétés mécaniques adaptables à celles du foie en fonction de l’état physiologique à reproduire (foie sain ou pathologique). Dans la première partie, nous développons et caractérisons le cryogel d’alginate au niveau microscopique et macroscopique, à l’extérieur (échantillons cylindriques) puis à l’intérieur de la biopuce. Trois paramètres sont étudiés ici : la température de cryopolymérisation, la concentration d’alginate ainsi que la quantité d’agents réticulants. Les propriétés mécaniques, la porosité, l’absorption, l’interconnectivité des pores et la résistance au flux sont analysés.La deuxième partie vise à cultiver des cellules hépatiques au sein de ce nouveau dispositif. Pour cette étude de faisabilité la lignée cellulaire HepG2/C3A est utilisée. Les résultats montrent des cellules viables et fonctionnelles (production d’albumine, transformation d’APAP). De plus, nous observons une structure tissulaire 3D, qui se maintient après retrait du cryogel d’alginate. La dernière partie a pour but de complexifier le modèle hépatique, notamment par des co-cultures. Pour se rapprocher de la structure du sinusoïde, des cellules hépatiques sont cultivées avec des cellules endothéliales (HUVEC) selon deux approches. De plus, la possibilité de suivre des cellules tumorales circulantes (MDA-MB-231) dans le système est étudiéeToday, one of the challenges for the pharmaceutical industry is to develop accurate in vitro liver models to improve the predictability of preclinical studies, in particular the study of the toxicity and efficacy of drug candidates. In recent years, tissue engineering, a multidisciplinary approach to develop tissues, has led to the development of new cell culture methods. Among them, cell cultures in 3D or in perfusion allowed to obtain hepatic activities similar to those observed in vivo. The objective of this thesis is to combine these two cell culture methods to create an even more accurate in vitro liver model. To do so, we are seeking to develop an alginate cryogel integrated into a microchip with mechanical properties adaptable to those of the liver depending on the physiological state to be reproduced (healthy or pathological liver).In the first part, we develop and characterize the alginate cryogel at the microscopic and macroscopic level, outside (cylindrical samples) and then inside the biochip. Three parameters are studied here: the cryopolymerization temperature, the alginate concentration and the quantity of cross-linking agents. Mechanical properties, porosity, absorption, pore interconnectivity and flow resistance are analyzed. The second part aims to culture liver cells within this new device. For this feasibility study the HepG2/C3A cell line is used. The results show viable and functional cells (albumin production, APAP transformation). In addition, we observe a 3D tissue structure, which is maintained after removal of the alginate cryogel. The last part aims to complexify the hepatic model, in particular by co-cultures. To get closer to the sinusoid structure, liver cells are cultured with endothelial cells (HUVEC) according to two approaches. In addition, the possibility to follow circulating tumor cells (MDA-MB-231) in the system is studied
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Krammer, Thibault. "Développement d'un réseau microvasculaire sur puce microfluidique pour la reconstruction tissulaire." Thesis, Université Grenoble Alpes (ComUE), 2019. http://www.theses.fr/2019GREAV044.
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L’ingénierie tissulaire vise à développer in vitro des tissus fonctionnels ou des organes afin de fournir des plateformes de tests de médicaments ou des tissus transplantables et améliorer les traitements fournis aux patients. Cependant, les constructions tissulaires physiologiques développées à ce jour n’intègrent pas un réseau vasculaire perfusable. In vivo, le réseau vasculaire approvisionne les cellules de l’organisme en oxygène et nutriments et évacue les déchets cellulaires et le dioxyde de carbone. Il possède également un rôle prépondérant dans le maintien de l’homéostasie des organes. L’approvisionnement des cellules s’effectue au niveau des capillaires sanguins : vaisseaux creux dont la paroi est uniquement composée d’une couche de cellules endothéliales. Le réseau de capillaires sanguins est un réseau dense perfusant l’ensemble des tissus de l’organisme. De par la limite de diffusion de l’oxygène dans les tissus, chaque cellule est située au maximum à 200 µm d’un capillaire. Les difficultés de construction d’un réseau de capillaires sanguins perfusable et d’intégration au sein de constructions tissulaires limitent le développement de tissus physiologiques épais.Une technique innovante de développement d’un réseau microvasculaire à l’intérieur d’une construction épaisse est présentée dans cette thèse. Cette technique consiste en l’assemblage de micro-unités tissulaires sphériques au sein d’une chambre microfluidique, et en le développement d’un réseau de capillaires au niveau des pores interstitiels formés par l’empilement de sphères. Les micro-unités tissulaires sont composées de biopolymères représentatifs de la matrice extracellulaire et contiennent des cellules du tissu d’intérêt. Une couche de cellules endothéliales est développée à la surface de ces microsphères. L’empilement de ces microsphères crée un milieu poreux dans lequel du milieu nutritif est perfusé. Le contrôle de l’écoulement au sein d’une telle structure permet l’application de stimuli physiques influençant l’auto-assemblage des cellules endothéliales en capillaires au sein de l’espace interstitiel de l’empilement.Durant cette thèse, un dispositif de fabrication de microsphères à partir de biopolymères naturels a été développé. La structure formée par les empilements de sphères a été étudiée et les écoulements au sein de tels milieux ont été caractérisés de sorte à appliquer des stimuli physiques contrôlés aux cellules. Un système microfluidique de perfusion, de type bioréacteur, intégrant une chambre de développement a été fabriquée. Une construction tissulaire épaisse a pu être formée au sein de ce système et le développement du réseau vasculaire a été favorisé. La formation du réseau a été montrée par la présence de capillaires sanguins perfusés au sein de la structure. La technique développée promet une application au développement de nombreux tissus et des applications pour des dispositifs d’organes-sur-puces ou d’ingénierie tissulaireTissue engineering aims to develop functional tissues or organs in vitro in order to provide drug testing platforms or transplantable tissues and improve the treatments provided to patients. However, the physiological tissue structures developed to date do not integrate and perfusable vascular network. In vivo, the vascular network supplies the body’s cells with oxygen and nutrients and removes cellular waste and carbon dioxide. It also has a major role in maintaining organ homeostasis. Blood capillaries are hollow vessels whose walls are only composed of a layer of endothelial cells and diffuse nutrients. The blood capillary network is dense and perfuse all tissues. Due to the limit oxygen diffusion inside tissues, each cell is located at most 200µm away from a capillary. The difficulties of building a network of perfusable capillaries and integrating them into tissue constructs limit the development of thick physiological tissues.An innovative technique for developing a microvascular network within a thick construction is presented in this thesis. This technique consists of assembling spherical tissue micro-units within a microfluidic chamber, and developing a network of capillaries through the interstitial pores formed by the spheres packing. Tissue micro-units are composed of biopolymers representative of the extracellular matrix and contain cells from the tissue of interest. A layer of endothelial cells is developed on the surface of these microspheres. The stacking of these microspheres creates a porous medium in which nutrient medium is perfused. Flow control within such a structure allows the application of physical stimuli influencing the self-assembly of endothelial cells into capillaries within the interstitial space of the sphere packing.During this thesis, a device for manufacturing microspheres from natural biopolymers was developed. The structure formed by the stacks of spheres was studied and the flow within such environments were characterized so as to apply controlled physical stimuli to cells. A bioreactor-like perfusion system has been built. A thick tissue structure could be formed within this system and the development of the vascular network was promoted. The formation of the network was demonstrated by the presence of infused blood capillaries within the structure. The technique developed promises to be applied to the development of many tissues and applications for organ-on-chip or tissue engineering devices
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Essaouiba, Amal. "Development of a liver-pancreas in vitro model using microfluidic organ-on-chip technologies." Thesis, Compiègne, 2020. http://www.theses.fr/2020COMP2573.
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Le diabète mellitus, également désigné comme la maladie du siècle, est une pathologie mortelle qui affecte le système endocrinien. Les mécanismes liés à la rupture de la boucle de rétroaction, qui régule le métabolisme et induit le diabète, ne sont pas entièrement connus. La compréhension des mécanismes d'action de l'insuline est donc essentielle pour le développement de stratégies thérapeutiques efficaces afin du lutter contre cette maladie. Par conséquent, il est impératif de trouver un modèle robuste et fiable, capable de surmonter les limites de la culture cellulaire traditionnelle en 2D et de l'expérimentation animale, pour la recherche sur le diabète. L'objectif de cette thèse est de développer un nouveau modèle de co‐culture foie‐pancréas en utilisant des systèmes microphysiologiques avancés (MPs) afin d’aborder plus efficacement le mécanisme impliqué dans la régulation endocrinienne hépatique et pancréatique. Ce travail met en évidence la capacité des systèmes multi‐organes sur puce qui combinent la compartimentation avancée des cellules en 3D, la microfluidique et la technologie des cellules souches pluripotentes induites (iPSC), pour atteindre une complexité biologique élevée et des fonctions rarement reproduites par une seule de ces technologies d’ingénierie tissulaireDiabetes mellitus (DM) or the so called disease of the century is a life threatening dysfunction that affects the endocrine system. The mechanisms underlying the break in the feedback loop that regulates the metabolism and the consequent diabetes induction are not fully known. Understanding the mechanisms of insulin action is therefore crucial for the further development of effective therapeutic strategies to combat DM. Accordingly, it is imperative to find a robust and reliable model for diabetes research able to overcome the limitations of traditional 2D in vitro cell culture and animal experimentation. The aim of this thesis is to develop a new liver‐pancreas co‐culture model using advanced microphysiological systems (MPs) to tackle more effectively the mechanism involving the hepatic and pancreatic endocrine regulation. This work highlights the power of multi organ‐on‐chip systems that combines the advanced 3D‐cell compartmentalization, microfluidics and induced pluripotent stem cells (iPSC) technology to achieve a high biological complexity and functions that are rarely reproduced by only one of these tissue engineering technologies
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Shah, Pratikkumar. "Development of a Lab-on-a-Chip Device for Rapid Nanotoxicity Assessment In Vitro." FIU Digital Commons, 2014. http://digitalcommons.fiu.edu/etd/1834.
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Increasing useof nanomaterials in consumer products and biomedical applications creates the possibilities of intentional/unintentional exposure to humans and the environment. Beyond the physiological limit, the nanomaterialexposure to humans can induce toxicity. It is difficult to define toxicity of nanoparticles on humans as it varies by nanomaterialcomposition, size, surface properties and the target organ/cell line. Traditional tests for nanomaterialtoxicity assessment are mostly based on bulk-colorimetric assays. In many studies, nanomaterials have found to interfere with assay-dye to produce false results and usually require several hours or days to collect results. Therefore, there is a clear need for alternative tools that can provide accurate, rapid, and sensitive measure of initial nanomaterialscreening. Recent advancement in single cell studies has suggested discovering cell properties not found earlier in traditional bulk assays. A complex phenomenon, like nanotoxicity, may become clearer when studied at the single cell level, including with small colonies of cells. Advances in lab-on-a-chip techniques have played a significant role in drug discoveries and biosensor applications, however, rarely explored for nanomaterialtoxicity assessment. We presented such cell-integrated chip-based approach that provided quantitative and rapid response of cellhealth, through electrochemical measurements. Moreover, the novel design of the device presented in this study was capable of capturing and analyzing the cells at a single cell and small cell-population level. We examined the change in exocytosis (i.e. neurotransmitterrelease) properties of a single PC12 cell, when exposed to CuOand TiO2 nanoparticles. We found both nanomaterials to interfere with the cell exocytosis function. We also studied the whole-cell response of a single-cell and a small cell-population simultaneously in real-time for the first time. The presented study can be a reference to the future research in the direction of nanotoxicity assessment to develop miniature, simple, and cost-effective tool for fast, quantitative measurements at high throughput level. The designed lab-on-a-chip device and measurement techniques utilized in the present work can be applied for the assessment of othernanoparticles' toxicity, as well.
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Carvalho, Mariana Rodrigues de. "Tissue engineered in vitro models on a chip for cancer research." Doctoral thesis, 2019. http://hdl.handle.net/1822/64605.
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Tese de Doutoramento em Engenharia de Tecidos, Medicina Regenerativa e Células EstaminaisBy 2030, the global burden is expected to grow to 21.7 million new cancer cases and 13 million cancer deaths simply due to the growth and aging of the population. Among all types of cancer, colorectal cancer is a major cause of morbidity and mortality worldwide, and accounts for over 9 % of all cancer incidence. It is the third most common cancer worldwide and affects men and women equally. In order to win the battle against cancer, further advances are in great need to unveil identification of cancer-causing agents in in vitro and in vivo animal models, as well as for the development of personalized therapies, drug screening, and to provide insightful knowledge on the mechanisms of tumor growth and metastasis. Microfluidic devices, together with tissue engineering strategies and nanotechnology have emerged as a powerful platform to tackle the previously mentioned hurdles. These themes are the focus of Section 1, in Chapters I, II and III. In this thesis we focus on the application of CMCht/PAMAM dendrimer nanoparticles.as the synthesis, uptake efficiency/internalization and cytotoxic effect of fluorescent-labeled CMCht/PAMAM dendrimer nanoparticles was investigated using different cancer cell lines in both traditional culture flasks and under physiological flow inside a microfluidic platform (Chapter V). Other than nanoparticles, the use of different biomaterials to modulate 3D microenvironment of tumors is of the utmost importance. Therefore, the use of HRP-crosslinked SF hydrogels with spatial tunable properties was proposed in a colorectal cancer extravasation 3D model on a commercial chip Vena4™ (Chapter VI). To increase the complexity of the cancer models, a microfluidic chip was designed and fabricated for the incorporation of tumor and vascular parts, allowing for gradients of gemcitabine released from CMCht/PAMAM nanoparticles to be tested (Chapter VII). Chemical modification in the CMCht/PAMAM dendrimer nanoparticles in order to target colorectal cancer was also achieved in Chapter VIII. In Chapter IX, a new proof of concept consisting of a microfluidic silk platform, flexible and implantable, was developed in house. The results and platforms developed in this thesis are discussed in Chapter X and represent a strong advance in the field of lab-on-chip research and will be a useful tool for drug discovery and study of migration/metastasis phenomena, allowing for a versatile choice of tissues, biomaterials and biological assays.
Até 2030, o número global de novos casos de cancro deverá crescer para 21,7 milhões, com cerca de 13 milhões de mortes, simplesmente devido ao crescimento e envelhecimento da população. Entre todos os tipos de cancro, o cancro colorretal é uma das principais causas de morbidade e mortalidade em todo o mundo, representando mais de 9 % entre todos os tipos de cancro. Com o objectivo de ganhar a guerra contra o cancro, novos avanços são rapidamente precisos, a fim de identificar, em modelos animais in vitro e in vivo os agentes causadores de cancro, bem como para o desenvolvimento de terapias personalizadas, teste de novos fármacos e aumentar o conhecimento actual sobre os mecanismos de crescimento tumoral e metástases. Dispositivos de microfluídica juntamente com estratégias de engenharia de tecidos e nanotecnologia surgiram como uma poderosa plataforma para lidar com os obstáculos mencionados anteriormente. Esses temas são o foco da Secção 1, nos Capítulos I, II e III. Nesta tese damos enfâse à aplicação de nanopartículas CMCht/PAMAM. A síntese, eficiência, internalização e efeito citotóxico das mesmas foram investigados usando diferentes linhas de células tumorais em frascos de cultura tradicionais e dentro de uma plataforma microfluídica (Capítulo V). Além das nanopartículas, o uso de diferentes biomateriais para modular o microambiente 3D de tumores é de extrema importância. Portanto, o uso de hidrogéis SF reticulados com HRP com propriedades mecânicas ajustáveis foi proposto num modelo 3D de extravasamento de cancro colorretal num chip comercial VenaT4™ (Capítulo VI). Para aumentar a complexidade dos modelos de cancro em chips, uma plataforma microfluídica foi projetada e fabricada para a incorporação de ambas as partes tumorais e vasculares, permitindo testar gradientes de gemcitabina libertados das nanopartículas CMCht/PAMAM (Capítulo VII). Modificações químicas nas nanopartículas para atingir especificamente células cancerígenas também foram alcançadas no Capítulo VIII. No Capítulo IX, uma nova prova de conceito consistindo numa plataforma microfluídica de seda, totalmente flexível e implantável, foi desenvolvida. Os resultados e plataformas desenvolvidos nesta tese representam um forte avanço no campo da investigação do cancro, e serão uma ferramenta útil para a descoberta de drogas e estudo de metastases, permitindo uma escolha versátil de tecidos, hidrogéis e ensaios biológicos.
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"Engineering an integrated microphysiological system for modeling human fibrotic disease." Tulane University, 2021.
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archives@tulane.eduFibrotic diseases comprise up to 45% of deaths in the industrialized world. Few effective anti-fibrotic therapeutics exist, due in part to the lack of human-relevant preclinical models. The goal of this research was to improve the modeling of fibrotic diseases in microphysiological systems (MPS) by engineering quiescence in cultured human fibroblasts prior to MPS incorporation. To create an assay for testing this approach, a versatile organ chip was designed while optimizing workflow for production of the organ chip molds with an SLA 3D printer. After identifying 2D culture conditions that repress fibroblast activation, we tested the hypothesis that the 2D culture protocol would impact the fibrotic baseline in our MPS. 3D confocal microscopy and multi-metric image analysis of immunostaining for cellular and extracellular matrix (ECM) components via intensity and pattern quantification revealed the establishment of more physiological baseline for MPS fibrosis models. To test in a disease-relevant context, we created a model of the stromal reaction in lung cancer using our organ chip and demonstrated that our integrated MPS can be used to quantify the fibrosis-inducing effects of cancer cells that drive stromal reactions.
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Max Wendell
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Javor, Josh. "BioMEMS for cardiac tissue monitoring and maturation." Thesis, 2021. https://hdl.handle.net/2144/42600.
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Diseases of the heart have been the most common cause of death in the United States since the middle of the 20th century. The development of engineered cardiac tissue over the last three decades has yielded human induced pluripotent stem cell-derived (hiPSC) cardiomyocytes (CMs), microscale “heart-on-a-chip” platforms, optical interrogation techniques, and more. Having spawned its own scientific field, ongoing research promises lofty goals to address the heart disease burden around the world, such as patient-specific disease models, and clinical trials on chip-based platforms. The greatest academic pursuit for engineered cardiac tissues is to increase their maturity, thereby increasing relevance to native adult tissue. Investigation of cardiomyocyte maturity necessitates the development of 3D-tissue compatible techniques for measuring and perturbing cardiac biology with enhanced precision.
This dissertation focuses on the development of biological microelectromechanical systems (BioMEMS) for precision measurement and perturbation of cardiac tissue. We discuss three unique approaches to interfacing MEMS-based tools with cardiac biology. The first is a high resolution magnetic sensor, which directly measures the spatial gradient of a magnetic field. This has an ideal application in magnetocardiography (MCG), as the flux of ions during cardiac contractions produces measurable magnetic signals around the tissue and can be leveraged for noncontact diagnosis. The second is a highly functionalized heart-on-a-chip platform, wherein the mechanical contractions of cardiac microtissues can be simultaneously recorded and actuated. Contractile dynamics are leading indicators of maturity in engineered cardiac tissue and mechanical conditioning has shown recent promise as a critical component of cardiac maturation. The third is the imaging of contractile nanostructures in engineered cardiomyocytes at depth in a 3D microtissue. We use small angle X-ray scattering (SAXS) to discern the periodic arrangement of myofilaments in their native 3D environment. We enable a significant structural analysis to provide insight for functional maturation. Enabling these three thrusts required developing two supporting technologies. The first is the engineered control of dynamic second order systems, a foundational element of all our MEMS and magnetic techniques. We demonstrate numerous algorithms to improve settling time or decrease dead-time such that samples with fast temporal effects can be measured. The second is a microscale gluing technique for integrating myriad of materials with MEMS devices, yielding unique sensors and actuators.2022-05-15T00:00:00Z
Books on the topic "Tissue-on-chip"
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Ramadan, Qasem, Massimo Alberti, Martin Dufva, and Yi-Chung Tung, eds. Medical and Industrial Applications of Microfluidic-based Cell/Tissue Culture and Organs-on-a-Chip: Advances in Organs-on-a-Chip and Organoids Technologies. Frontiers Media SA, 2019. http://dx.doi.org/10.3389/978-2-88963-114-8.
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Lepora, Nathan F. Biohybrid systems. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780199674923.003.0048.
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This chapter introduces the “biohybrid systems” section of the Handbook of Living Machines and briefly reviews some important examples of systems formed by coupling biological to engineered components. These include brain–machine interfaces, both non-invasive, using different external measurement and scanning devices, and invasive approaches focusing on implantable probes. Next we consider fabrication methods for micro- and nanobiohybrid systems and an example of a biohybrid system at the organism level, in the form of a robot–animal biohybrid, developed using methods from synthetic biology. There are many application for biohybrid systems in healthcare: we include exemplar chapters describing intelligent prostheses such as artificial hands with tactile sensing capabilities, sensory organ–chip hybrids in the form of cochlear implants, and artificial implants designed to replace damaged neural tissue and restore lost memory function.
Book chapters on the topic "Tissue-on-chip"
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Morimoto, Yuya, Nobuhito Mori, and Shoji Takeuchi. "In Vitro Tissue Construction for Organ-on-a-Chip Applications." In Bioanalysis, 247–74. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-6229-3_9.
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Wang, Zongjie, Roya Samanipour, and Keekyoung Kim. "Organ-on-a-Chip Platforms for Drug Screening and Tissue Engineering." In Biomedical Engineering: Frontier Research and Converging Technologies, 209–33. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-21813-7_10.
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Yoon, Jeong-Yeol. "Organ-on-a-Chip." In Tissue Engineering, 193–217. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-83696-2_11.
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Tong, Ziqiu, Wing-Yin Tong, Bo Peng, Yingkai Wei, Arianna Oddo, and Nicolas H. Voelcker. "Using Integrated Cancer-on-Chip Platforms to Emulate and Probe Various Cancer Models." In Nanotechnology Characterization Tools for Tissue Engineering and Medical Therapy, 151–204. Berlin, Heidelberg: Springer Berlin Heidelberg, 2019. http://dx.doi.org/10.1007/978-3-662-59596-1_4.
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Aboutalebianaraki, Nadia, Angela Shar, Madisyn Messmore, Kaylee Misiti, and Mehdi Razavi. "Musculoskeletal tissue-on-a-chip." In Principles of Human Organs-on-Chips, 407–28. Elsevier, 2023. http://dx.doi.org/10.1016/b978-0-12-823536-2.00010-9.
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Douglas, Kenneth. "Organs-on-a-Chip." In Bioprinting, 155–82. Oxford University Press, 2021. http://dx.doi.org/10.1093/oso/9780190943547.003.0010.
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Abstract: This chapter explores organs-on-a-chip, miniaturized bioprinted organ tissues enclosed in a microfluidic housing (microfluidics refers to very small-scale plumbing) that can mimic functions of human physiology or disease and are particularly effective when multiple tissue types—for example, lung, heart, and liver—can interact on the same chip. The chapter sets forth the historical evolution of organs-on-a-chip and instances several studies. In one investigation, experimenters found a totally unexpected result in which a drug produced an inflammation of lung tissue that in turn led to toxic results in nearby heart tissue. In another inquiry, researchers focused on a bioprinted, functional, airway-on-a-chip to characterize inflammatory diseases such as asthma and chronic obstructive lung disease and vet potential medications for their treatment. Their work included quantitative comparisons of normal lung tissue and asthmatic lung tissue to a variety of insults, including household dust mites.
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Shupe, Thomas, Aleksander Skardal, and Anthony Atala. "Body-on-a-chip: three-dimensional engineered tissue models." In Principles of Tissue Engineering, 1443–58. Elsevier, 2020. http://dx.doi.org/10.1016/b978-0-12-818422-6.00078-2.
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Pappalardo, Alberto, Alvarez Cespedes, Ha Linh Vu, and Hasan Erbil Abaci. "Advances in skin-on-a-chip and skin tissue engineering." In Principles of Human Organs-on-Chips, 123–66. Elsevier, 2023. http://dx.doi.org/10.1016/b978-0-12-823536-2.00005-5.
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Çakır Hatır, Pınar. "Biomedical Nanotechnology." In Research Anthology on Emerging Technologies and Ethical Implications in Human Enhancement, 634–62. IGI Global, 2021. http://dx.doi.org/10.4018/978-1-7998-8050-9.ch033.
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This chapter aims to provide an overview of recent studies in the field of biomedical nanotechnology, which is described as the combination of biology and nanotechnology. The field includes innovations such as the improvement of biological processes at the nanoscale, the development of specific biomaterials, and the design of accurate measurement devices. Biomedical nanotechnology also serves areas like the development of intelligent drug delivery systems and controlled release systems, tissue engineering, nanorobotics (nanomachines), lab-on-a-chip, point of care, and nanobiosensor development. This chapter will mainly cover the biomedical applications of nanotechnology under the following titles: the importance of nanotechnology, the history of nanotechnology, classification of nanostructures, inorganic, polymer and composite nanostructures, fabrication of nanomaterials, applications of nanostructures, the designs of intelligent drug delivery systems and controlled release systems, bioimaging, bioseparation, nano-biomolecules, lab-on-a-chip, point of care, nanobiosensor development, tissue engineering and the future of biomedical nanotechnology.
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Çakır Hatır, Pınar. "Biomedical Nanotechnology." In Biomedical and Clinical Engineering for Healthcare Advancement, 30–65. IGI Global, 2020. http://dx.doi.org/10.4018/978-1-7998-0326-3.ch003.
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This chapter aims to provide an overview of recent studies in the field of biomedical nanotechnology, which is described as the combination of biology and nanotechnology. The field includes innovations such as the improvement of biological processes at the nanoscale, the development of specific biomaterials, and the design of accurate measurement devices. Biomedical nanotechnology also serves areas like the development of intelligent drug delivery systems and controlled release systems, tissue engineering, nanorobotics (nanomachines), lab-on-a-chip, point of care, and nanobiosensor development. This chapter will mainly cover the biomedical applications of nanotechnology under the following titles: the importance of nanotechnology, the history of nanotechnology, classification of nanostructures, inorganic, polymer and composite nanostructures, fabrication of nanomaterials, applications of nanostructures, the designs of intelligent drug delivery systems and controlled release systems, bioimaging, bioseparation, nano-biomolecules, lab-on-a-chip, point of care, nanobiosensor development, tissue engineering and the future of biomedical nanotechnology.
Conference papers on the topic "Tissue-on-chip"
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Goyal, Girija, Jaclyn Long, and Donald E. Ingber. "Abstract A76: Microenginered human lymphoid tissue on chip." In Abstracts: AACR Special Conference on Tumor Immunology and Immunotherapy; October 1-4, 2017; Boston, MA. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/2326-6074.tumimm17-a76.
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Poulikakos, L. V., S. Bordy, J. Byun, Z. Haddadin, P. Kirya, S. Khan, D. Y. Kim, et al. "Colorimetric Metasurfaces for Quantitative, On-Chip Tissue Diagnostics." In CLEO: Science and Innovations. Washington, D.C.: Optica Publishing Group, 2022. http://dx.doi.org/10.1364/cleo_si.2022.sth5j.7.
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We leverage the unique properties of anisotropic, colorimetric metasurfaces to selectively visualize disease-relevant fiber density and orientation in biological tissue, paving the way toward rapid, precise and low-cost diagnostics ranging from cancer to neurodegenerative disease.
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Zhang, Yibo, Yoonjung Shin, Kevin Sung, Sam Yang, Harrison Chen, Hongda Wang, Da Teng, et al. "3D on-chip microscopy of optically cleared tissue." In Optics and Biophotonics in Low-Resource Settings IV, edited by David Levitz, Aydogan Ozcan, and David Erickson. SPIE, 2018. http://dx.doi.org/10.1117/12.2290558.
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Jin, Laidi, Tian Tian, Danyang Liu, Hongjv Mao, and Huiying Liu. "·Reconstituting Organ-Level Periodontal Soft Tissue on a Chip." In 2021 21st International Conference on Solid-State Sensors, Actuators and Microsystems (Transducers). IEEE, 2021. http://dx.doi.org/10.1109/transducers50396.2021.9495506.
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Okino, Yuki, Toshifumi Asano, and Keisuke Morishima. "Molecular dynamics of orientation controlled muscle tissue on a chip." In 2015 International Symposium on Micro-NanoMechatronics and Human Science (MHS). IEEE, 2015. http://dx.doi.org/10.1109/mhs.2015.7438346.
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Balciunas, Evaldas, Linas Jonusauskas, Vytautas Valuckas, Daiva Baltriukiene, Virginija Bukelskiene, Roaldas Gadonas, and Mangirdas Malinauskas. "Lithographic microfabrication of biocompatible polymers for tissue engineering and lab-on-a-chip applications." In SPIE Photonics Europe, edited by Jürgen Popp, Wolfgang Drexler, Valery V. Tuchin, and Dennis L. Matthews. SPIE, 2012. http://dx.doi.org/10.1117/12.923042.
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Woon Tiong Ang, Changhong Yu, Jie Chen, Tarek El-Bialy, Michael Doschak, Hasan Uludag, and Ying Tsui. "System-on-chip ultrasonic transducer for dental tissue formation and stem cell growth and differentiation." In 2008 IEEE International Symposium on Circuits and Systems - ISCAS 2008. IEEE, 2008. http://dx.doi.org/10.1109/iscas.2008.4541793.
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Dias, R. A., J. H. Correia, and G. Minas. "On-Chip Integrated Optical Sensors for Fluorescence Detection of Cancer Tissue: Application to Capsule Endoscopy." In 2007 14th IEEE International Conference on Electronics, Circuits and Systems (ICECS '07). IEEE, 2007. http://dx.doi.org/10.1109/icecs.2007.4511020.
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Yoo, Kyoung Min, and Ray T. Chen. "On-Chip Si3N4 Spatial Heterodyne Fourier Transform Spectrometer for the Optical Window in Biological Tissue." In CLEO: Applications and Technology. Washington, D.C.: OSA, 2021. http://dx.doi.org/10.1364/cleo_at.2021.jtu3a.122.
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Tourlomousis, Filippos, and Robert C. Chang. "Computational Modeling of 3D Printed Tissue-on-a-Chip Microfluidic Devices as Drug Screening Platforms." In ASME 2014 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2014. http://dx.doi.org/10.1115/imece2014-38454.
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Physiological tissue-on-a-chip technology is enabled by adapting microfluidics to create micro scale drug screening platforms that replicate the complex drug transport and reaction processes in the human liver. The ability to incorporate three-dimensional (3d) tissue models using layered fabrication approaches into devices that can be perfused with drugs offer an optimal analog of the in vivo scenario. The dynamic nature of such in vitro metabolism models demands reliable numerical tools to determine the optimum tissue fabrication process, flow, material, and geometric parameters for the most effective metabolic conversion of the perfused drug into the liver microenvironment. Thus, in this modeling-based study, the authors focus on modeling of in vitro 3d microfluidic microanalytical microorgan devices (3MD), where the human liver analog is replicated by 3d cell encapsulated alginate hydrogel based tissue-engineered constructs. These biopolymer constructs are hosted in the chamber of the 3MD device serving as walls of the microfluidic array of channels through which a fluorescent drug substrate is perfused into the microfluidic printed channel walls at a specified volumetric flow rate assuring Stokes flow conditions (Re<<1). Due to the porous nature of the hydrogel walls, a metabolized drug product is collected as an effluent stream at the outlet port. A rigorous modeling approached aimed to capture both the macro and micro scale transport phenomena is presented. Initially, the Stokes Flow Equations (free flow regime) are solved in combination with the Brinkman Equations (porous flow regime) for the laminar velocity profile and wall shear stresses in the whole shear mediated flow regime. These equations are then coupled with the Convection-Diffusion Equation to yield the drug concentration profile by incorporating a reaction term described by the Michael-Menten Kinetics model. This effectively yields a convection-diffusion–cell kinetics model (steady state and transient), where for the prescribed process and material parameters, the drug concentration profile throughout the flow channels can be predicted. A key consideration that is addressed in this paper is the effect of cell mechanotransduction, where shear stresses imposed on the encapsulated cells alter the functional ability of the liver cell enzymes to metabolize the drug. Different cases are presented, where cells are incorporated into the geometric model either as voids that experience wall shear stress (WSS) around their membrane boundaries or as solid materials, with linear elastic properties. As a last step, transient simulations are implemented showing that there exists a tradeoff with respect the drug metabolized effluent product between the shear stresses required and the residence time needed for drug diffusion.
Reports on the topic "Tissue-on-chip"
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Eshed-Williams, Leor, and Daniel Zilberman. Genetic and cellular networks regulating cell fate at the shoot apical meristem. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7699862.bard.
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The shoot apical meristem establishes plant architecture by continuously producing new lateral organs such as leaves, axillary meristems and flowers throughout the plant life cycle. This unique capacity is achieved by a group of self-renewing pluripotent stem cells that give rise to founder cells, which can differentiate into multiple cell and tissue types in response to environmental and developmental cues. Cell fate specification at the shoot apical meristem is programmed primarily by transcription factors acting in a complex gene regulatory network. In this project we proposed to provide significant understanding of meristem maintenance and cell fate specification by studying four transcription factors acting at the meristem. Our original aim was to identify the direct target genes of WUS, STM, KNAT6 and CNA transcription factor in a genome wide scale and the manner by which they regulate their targets. Our goal was to integrate this data into a regulatory model of cell fate specification in the SAM and to identify key genes within the model for further study. We have generated transgenic plants carrying the four TF with two different tags and preformed chromatin Immunoprecipitation (ChIP) assay to identify the TF direct target genes. Due to unforeseen obstacles we have been delayed in achieving this aim but hope to accomplish it soon. Using the GR inducible system, genetic approach and transcriptome analysis [mRNA-seq] we provided a new look at meristem activity and its regulation of morphogenesis and phyllotaxy and propose a coherent framework for the role of many factors acting in meristem development and maintenance. We provided evidence for 3 different mechanisms for the regulation of WUS expression, DNA methylation, a second receptor pathway - the ERECTA receptor and the CNA TF that negatively regulates WUS expression in its own domain, the Organizing Center. We found that once the WUS expression level surpasses a certain threshold it alters cell identity at the periphery of the inflorescence meristem from floral meristem to carpel fate [FM]. When WUS expression highly elevated in the FM, the meristem turn into indeterminate. We showed that WUS activate cytokinine, inhibit auxin response and represses the genes required for root identity fate and that gradual increase in WUCHEL activity leads to gradual meristem enlargement that affect phyllotaxis. We also propose a model in which the direction of WUS domain expansion laterally or upward affects meristem structure differently. We preformed mRNA-seq on meristems with different size and structure followed by k-means clustering and identified groups of genes that are expressed in specific domains at the meristem. We will integrate this data with the ChIP-seq of the 4 TF to add another layer to the genetic network regulating meristem activity.
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Ginzberg, Idit, and Walter De Jong. Molecular genetic and anatomical characterization of potato tuber skin appearance. United States Department of Agriculture, September 2008. http://dx.doi.org/10.32747/2008.7587733.bard.
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Potato (Solanum tuberosum L.) skin is composed of suberized phellem cells, the outer component of the tuber periderm. The focus of the proposed research was to apply genomic approaches to identify genes that control tuber skin appearance - smooth and shiny skin is highly preferred by the customers while russeted/netted skin potatoes are rejected. The breeding program (at Cornell University) seeks to develop smooth-skin varieties but has encountered frequent difficulties as inheritance of russeting involves complementary action by independently segregating genes, where a dominant allele at each locus is required for any degree of skin russeting. On the other hand, smooth-skin varieties frequently develop unsightly russeting in response to stress conditions, mainly high soil temperatures. Breeding programs in Israel aimed towards the improvement of heat tolerant varieties include skin quality as one of the desired characteristics. At the initiation of the present project it was unclear whether heat induced russeting and genetically inherited russeting share the same genes and biosynthesis pathways. Nevertheless, it has been suggested that russeting might result from increased periderm thickness, from strong cohesion between peridermal cells that prevents the outer layers from sloughing off, or from altered suberization processes in the skin. Hence, the original objectives were to conduct anatomical study of russet skin development, to isolate skin and russeting specific genes, to map the loci that determine the russet trait, and to compare with map locations the candidate russet specific genes, as well as to identify marker alleles that associated with russet loci. Anatomical studies suggested that russet may evolve from cracking at the outer layers of the skin, probably when skin development doesn’t meet the tuber expansion rate. Twodimensional gel electrophoresis and transcript profiling (cDNA chip, potato functional genomic project) indicated that in comparison to the parenchyma tissue, the skin is enriched with proteins/genes that are involved in the plant's responses to biotic and abiotic stresses and further expand the concept of the skin as a protective tissue containing an array of plantdefense components. The proteomes of skin from heat stressed tubers and native skin didn’t differ significantly, while transcript profiling indicated heat-related increase in three major functional groups: transcription factors, stress response and protein degradation. Exceptional was ACC synthase isogene with 4.6 fold increased level in the heat stressed skin. Russeting was mapped to two loci: rusB on chromosome 4 and rusC on chromosome 11; both required for russeting. No evidence was found for a third locus rusA that was previously proposed to be required for russeting. In an effort to find a link between the russeting character and the heat-induced russeting an attempt was made to map five genes that were found in the microarray experiment to be highly induced in the skin under heat stress in the segregating russet population. Only one gene was polymorphic; however it was localized to chromosome 2, so cannot correspond to rusB or rusC. Evaluation of AFLP markers tightly linked to rusB and rusC showed that these specific alleles are not associated with russeting in unrelated germplasm, and thus are not useful for MAS per se. To develop markers useful in applied breeding, it will be necessary to screen alleles of additional tightly linked loci, as well as to identify additional russet (heat-induced and/or native) related genes.