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Development of 3D In Vitro Liver Tumor Models Using Engineered Polymeric Microparticles for Drug Screening Applications.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Development of 3D In Vitro Liver Tumor Models Using Engineered Polymeric Microparticles for Drug Screening Applications./
Author:	Mansouri, Mona.
Description:	1 online resource (319 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 84-11, Section: B.
Contained By:	Dissertations Abstracts International84-11B.
Subject:	Biomedical engineering. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30509630click for full text (PQDT)
ISBN:	9798379442071

Development of 3D In Vitro Liver Tumor Models Using Engineered Polymeric Microparticles for Drug Screening Applications.
Mansouri, Mona.

Development of 3D In Vitro Liver Tumor Models Using Engineered Polymeric Microparticles for Drug Screening Applications. - 1 online resource (319 pages)

Source: Dissertations Abstracts International, Volume: 84-11, Section: B.

Thesis (Ph.D.)--The University of Akron, 2023.

Includes bibliographical references

Since the emergence of spheroid/organoid technology, a significant amount of effort has gone toward improving culture techniques to better recapitulate the native organ and preserve cell phenotype. While hydrogels of various compositions offer interesting opportunities to model human physiology, there are still un-optimized factors to consider in continuing to move the field forward. The goals of this PhD dissertation are (1) to engineer a defined microenvironment that can support the malignant state, function, and phenotype of liver cancer cells (2) to justify the developed liver model's application for in vitro drug screening that is predictive of patient responses. The focus is on key microenvironmental parameters affecting the physiological function of cells, mainly oxygenation and extracellular matrix ligands. To this end, monodispersed and cell-sized chitosan-based microparticles conjugated with fluorine molecules were generated using a custom microfluidic device. Next, they were co-cultured with commonly used human hepatocellular carcinoma cell line (HepG2) and hepatic stellate cells (HSCs) to enhance oxygen levels in aggregate culture. In the next step, the surface of microparticles was decorated with different ligands derived from the native liver extracellular matrix to understand how different proteins modulate cellular behavior. Finally, two tumor models including immortalized and patient-derived liver spheroids cultured with microparticles were applied for toxicity assessments in vitro and the mechanism underlying cell apoptosis was studied. Together, this dissertation advances efforts to create more physiologically relevant organ models and allows a well-defined condition and phenotypic cell signaling to improve the relevance of spheroid and organoid models.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798379442071Subjects--Topical Terms:

535387
Biomedical engineering.
Subjects--Index Terms:

Extracellular matrix ligandsIndex Terms--Genre/Form:

542853
Electronic books.

Development of 3D In Vitro Liver Tumor Models Using Engineered Polymeric Microparticles for Drug Screening Applications.
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500 $a Advisor: Leipzig, Nic D.
502 $a Thesis (Ph.D.)--The University of Akron, 2023.
504 $a Includes bibliographical references
520 $a Since the emergence of spheroid/organoid technology, a significant amount of effort has gone toward improving culture techniques to better recapitulate the native organ and preserve cell phenotype. While hydrogels of various compositions offer interesting opportunities to model human physiology, there are still un-optimized factors to consider in continuing to move the field forward. The goals of this PhD dissertation are (1) to engineer a defined microenvironment that can support the malignant state, function, and phenotype of liver cancer cells (2) to justify the developed liver model's application for in vitro drug screening that is predictive of patient responses. The focus is on key microenvironmental parameters affecting the physiological function of cells, mainly oxygenation and extracellular matrix ligands. To this end, monodispersed and cell-sized chitosan-based microparticles conjugated with fluorine molecules were generated using a custom microfluidic device. Next, they were co-cultured with commonly used human hepatocellular carcinoma cell line (HepG2) and hepatic stellate cells (HSCs) to enhance oxygen levels in aggregate culture. In the next step, the surface of microparticles was decorated with different ligands derived from the native liver extracellular matrix to understand how different proteins modulate cellular behavior. Finally, two tumor models including immortalized and patient-derived liver spheroids cultured with microparticles were applied for toxicity assessments in vitro and the mechanism underlying cell apoptosis was studied. Together, this dissertation advances efforts to create more physiologically relevant organ models and allows a well-defined condition and phenotypic cell signaling to improve the relevance of spheroid and organoid models.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2023
538 $a Mode of access: World Wide Web
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650 4 $a Chemical engineering. $3 560457
650 4 $a Cellular biology. $3 3172791
650 4 $a Oncology. $3 751006
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653 $a Fluorine molecules
653 $a Liver tumor models
653 $a Drug screening
653 $a Microfluidic device
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690 $a 0541
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710 2 $a The University of Akron. $b Chemical Engineering. $3 2094126
773 0 $t Dissertations Abstracts International $g 84-11B.
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