Application of Micro-Engineered Kidney, Liver, and Respiratory System Models to Accelerate Preclinical Drug Testing and Development

doi:10.3390/bioengineering9040150

Review

. 2022 Apr 2;9(4):150.

doi: 10.3390/bioengineering9040150.

Application of Micro-Engineered Kidney, Liver, and Respiratory System Models to Accelerate Preclinical Drug Testing and Development

Hanieh Gholizadeh^{1

2

3}, Shaokoon Cheng³, Agisilaos Kourmatzis⁴, Hanwen Xing⁵, Daniela Traini^{1

2}, Paul M Young^{2

6}, Hui Xin Ong^{1

2}

Affiliations

¹ Macquarie Medical School, Faculty of Medicine, Health, and Human Sciences, Macquarie University, Ryde, NSW 2109, Australia.
² Respiratory Technology, The Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW 2037, Australia.
³ School of Engineering, Faculty of Science and Engineering, Macquarie University, Ryde, NSW 2113, Australia.
⁴ School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Sydney, NSW 2006, Australia.
⁵ Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, NSW 2007, Australia.
⁶ Department of Marketing, Macquarie Business School, Macquarie University, Ryde, NSW 2109, Australia.

PMID: 35447710
PMCID: PMC9025644
DOI: 10.3390/bioengineering9040150

Review

Application of Micro-Engineered Kidney, Liver, and Respiratory System Models to Accelerate Preclinical Drug Testing and Development

Hanieh Gholizadeh et al. Bioengineering (Basel). 2022.

. 2022 Apr 2;9(4):150.

doi: 10.3390/bioengineering9040150.

Authors

Hanieh Gholizadeh^{1

2

3}, Shaokoon Cheng³, Agisilaos Kourmatzis⁴, Hanwen Xing⁵, Daniela Traini^{1

2}, Paul M Young^{2

6}, Hui Xin Ong^{1

2}

Affiliations

¹ Macquarie Medical School, Faculty of Medicine, Health, and Human Sciences, Macquarie University, Ryde, NSW 2109, Australia.
² Respiratory Technology, The Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW 2037, Australia.
³ School of Engineering, Faculty of Science and Engineering, Macquarie University, Ryde, NSW 2113, Australia.
⁴ School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Sydney, NSW 2006, Australia.
⁵ Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, NSW 2007, Australia.
⁶ Department of Marketing, Macquarie Business School, Macquarie University, Ryde, NSW 2109, Australia.

PMID: 35447710
PMCID: PMC9025644
DOI: 10.3390/bioengineering9040150

Abstract

Developing novel drug formulations and progressing them to the clinical environment relies on preclinical in vitro studies and animal tests to evaluate efficacy and toxicity. However, these current techniques have failed to accurately predict the clinical success of new therapies with a high degree of certainty. The main reason for this failure is that conventional in vitro tissue models lack numerous physiological characteristics of human organs, such as biomechanical forces and biofluid flow. Moreover, animal models often fail to recapitulate the physiology, anatomy, and mechanisms of disease development in human. These shortfalls often lead to failure in drug development, with substantial time and money spent. To tackle this issue, organ-on-chip technology offers realistic in vitro human organ models that mimic the physiology of tissues, including biomechanical forces, stress, strain, cellular heterogeneity, and the interaction between multiple tissues and their simultaneous responses to a therapy. For the latter, complex networks of multiple-organ models are constructed together, known as multiple-organs-on-chip. Numerous studies have demonstrated successful application of organ-on-chips for drug testing, with results comparable to clinical outcomes. This review will summarize and critically evaluate these studies, with a focus on kidney, liver, and respiratory system-on-chip models, and will discuss their progress in their application as a preclinical drug-testing platform to determine in vitro drug toxicology, metabolism, and transport. Further, the advances in the design of these models for improving preclinical drug testing as well as the opportunities for future work will be discussed.

Keywords: body-on-chip; disease-on-chip; drug discovery; drug transport; metabolism; organ-on-chip; toxicology.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
A summary of the investigations on three important drug assessments: drug metabolism, toxicology, and drug transport using liver-, kidney-, and lung-on-chip models. The figure summarizes the advantages of these organ-on-chip models to enhance drug testing.

**Figure 2**
The biomechanical cues emulated by kidney-, liver-, and respiratory-system-on-chips and the summary of the observations in terms of the effects on the cellular morphology, permeability, and drug response. Figure is created with BioRender.com.

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References

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[1] McGonigle P., Ruggeri B. Animal models of human disease: Challenges in enabling translation. Biochem. Pharmacol. 2014;87:162–171. doi: 10.1016/j.bcp.2013.08.006. - DOI - PubMed

[2] McGonigle P., Ruggeri B. Animal models of human disease: Challenges in enabling translation. Biochem. Pharmacol. 2014;87:162–171. doi: 10.1016/j.bcp.2013.08.006. - DOI - PubMed

[3] Khetani S.R., Bhatia S.N. Microscale culture of human liver cells for drug development. Nat. Biotechnol. 2008;26:120–126. doi: 10.1038/nbt1361. - DOI - PubMed

[4] Khetani S.R., Bhatia S.N. Microscale culture of human liver cells for drug development. Nat. Biotechnol. 2008;26:120–126. doi: 10.1038/nbt1361. - DOI - PubMed

[5] Esch E.W., Bahinski A., Huh D. Organs-on-chips at the frontiers of drug discovery. Nat. Rev. Drug Discoov. 2015;14:248–260. doi: 10.1038/nrd4539. - DOI - PMC - PubMed

[6] Esch E.W., Bahinski A., Huh D. Organs-on-chips at the frontiers of drug discovery. Nat. Rev. Drug Discoov. 2015;14:248–260. doi: 10.1038/nrd4539. - DOI - PMC - PubMed

[7] Wu Q., Liu J., Wang X., Feng L., Wu J., Zhu X., Wen W., Gong X. Organ-on-a-chip: Recent breakthroughs and future prospects. Biomed. Eng. Online. 2020;19:1–19. doi: 10.1186/s12938-020-0752-0. - DOI - PMC - PubMed

[8] Wu Q., Liu J., Wang X., Feng L., Wu J., Zhu X., Wen W., Gong X. Organ-on-a-chip: Recent breakthroughs and future prospects. Biomed. Eng. Online. 2020;19:1–19. doi: 10.1186/s12938-020-0752-0. - DOI - PMC - PubMed

[9] Kimura H., Sakai Y., Fujii T. Organ/body-on-a-chip based on microfluidic technology for drug discovery. Drug Metab. Pharmacok. 2018;33:43–48. doi: 10.1016/j.dmpk.2017.11.003. - DOI - PubMed

[10] Kimura H., Sakai Y., Fujii T. Organ/body-on-a-chip based on microfluidic technology for drug discovery. Drug Metab. Pharmacok. 2018;33:43–48. doi: 10.1016/j.dmpk.2017.11.003. - DOI - PubMed

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Application of Micro-Engineered Kidney, Liver, and Respiratory System Models to Accelerate Preclinical Drug Testing and Development

Affiliations

Application of Micro-Engineered Kidney, Liver, and Respiratory System Models to Accelerate Preclinical Drug Testing and Development

Authors

Affiliations

Abstract

Conflict of interest statement

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