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Kidney on a Chip Development and Drug Efficacy Testing for Renal Hypoxic Reperfusion Injury

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Abstract
The microphysiological system (MPS), dynamic complex cell culture technology has the ability
to mimic the human pathophysiological system. The main goal of MPS is to recreate
physiologically relevant human diseases to improve drug efficacy and unknown mechanism of
disease conditions. The significance of MPS is to mimic the human pathophysiological system to
replace animals, patient-relevant data, high precision-low toxicity, and save money and time.
Moreover, animal models have limitations to mimic human physiology and human disease
conditions. The MPS has the capacity to perform conventional bioassays including western blot,
ELISA, qRT-PCR, flow cytometry, biochemical assays and embedded sensors assays. Human
kidneys are responsible for filtration, filtering blood and removing waste materials, the kidney is
the vital organ for drug screening, efficacy, and toxicity studies. The hypoxic condition can affect
renal function, predominantly homeostasis, blood pressure, the balance of electrolytes, body fluids
and pH. Finally, the hypoxic condition leads to chronic kidney disease (CKD) and other organ
diseases as well. The renal hypoxic condition is challenging to perform in an animal model due to
the lack of a human pathophysiological system, ethical concerns, intraspecies genetic variations,
lack of robustness, and time and money. This thesis work encloses the advancement of the
microphysiological system for renal hypoxic reperfusion injury model and drug efficacy test to
overcome the current limitations of an animal model. Renal MPS was incorporated with
impedance-based transepithelial-endothelial electrochemical resistance (TEER) for real-time
monitoring of renal normoxic conditions, hypoxic conditions, and drug efficacy. Furthermore,
TEER data was incorporated with conventional assays for further validation. This thesis can serve
as a replacement for animals to improve drug discovery and disease models.
Author(s)
Chethikkattuveli Salih Abdul Rahim
Issued Date
2023
Awarded Date
2023-02
Type
Dissertation
URI
https://dcoll.jejunu.ac.kr/common/orgView/000000011102
Alternative Author(s)
케시카누벨리 살리
Affiliation
Graduate School Jeju National University
Department
대학원 메카트로닉스공학과
Advisor
Choi Kyung Hyun
Table Of Contents
1. Objectives of Thesis 1
2. Introduction 2
3. Research Background 5
3.1 Impact of Serum Concentration in Cell Culture Media 5
3.2 Extracellular Matrix Optimization for Microphysiological System 7
3.3 Renal Microphysiological System 9
4. Methodology 10
4.1 MPS Design and Development 11
4.2 Renal MPS Cell Culture 14
4.3 Renal Hypoxic reperfusion Injury on a Chip Model Development 16
4.4 Proximal Tubule Permeability Assay 17
4.5 TEER apparatus and assessment method 17
4.6 Drug Efficacy Testing on a Chip 20
4.7 Biochemical Assays. 20
4.7.1 Cell Viability Assay, Dicholorodihydroflourescein Diacetate Staining and Image Processing 20
4.7.2 Elisa Assay for Renal Biomarkers 21
5. Results and Discussion 21
5.1 Renal hypoxic Reperfusion Injury on a Chip Model 21
5.2 Impact of Renal hypoxic Injury on Proximal Tubule Barrier Integrity 25
5.3 Proximal Tubule Permeability Assay 27
5.4 Renal Hypoxic Injury Biomarkers Analysis 28
5.5 Drug Efficacy and Biomarkers Analysis 31
6. Conclusion and Future Perspectives 33
7. Reference 34
Degree
Doctor
Publisher
Graduate School Jeju National University
Citation
Chethikkattuveli Salih Abdul Rahim. (2023). Kidney on a Chip Development and Drug Efficacy Testing for Renal Hypoxic Reperfusion Injury.
Appears in Collections:
Faculty of Applied Energy System > Mechatronics Engineering
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