TY - JOUR
T1 - Modular Microphysiological System for Modeling of Biologic Barrier Function
AU - Ishahak, Matthew
AU - Hill, Jordan
AU - Amin, Quratulain
AU - Wubker, Laura
AU - Hernandez, Adiel
AU - Mitrofanova, Alla
AU - Sloan, Alexis
AU - Fornoni, Alessia
AU - Agarwal, Ashutosh
N1 - Funding Information:
Funding. This work was supported by NIDDK-supported Human Islet Research Network (HIRN, RRID: SCR_014393 ; https://hirnetwork.org ; UC4DK104209 and UG3DK122638 to AA). MI was supported by F31DK118860-01A1. AF was supported by the NIH grants R01DK117599, R01DK104753, R01CA227493, U54KD083912, UM1DK100846, U01DK116101, and UL1TR000460 (Miami Clinical Translational Science Institute).
PY - 2020/11/12
Y1 - 2020/11/12
N2 - Microphysiological systems, also known as organs-on-chips, are microfluidic devices designed to model human physiology in vitro. Polydimethylsiloxane (PDMS) is the most widely used material for organs-on-chips due to established microfabrication methods, and properties that make it suitable for biological applications such as low cytotoxicity, optical transparency, gas permeability. However, absorption of small molecules and leaching of uncrosslinked oligomers might hinder the adoption of PDMS-based organs-on-chips for drug discovery assays. Here, we have engineered a modular, PDMS-free microphysiological system that is capable of recapitulating biologic barrier functions commonly demonstrated in PDMS-based devices. Our microphysiological system is comprised of a microfluidic chip to house cell cultures and pneumatic microfluidic pumps to drive flow with programmable pressure and shear stress. The modular architecture and programmable pumps enabled us to model multiple in vivo microenvironments. First, we demonstrate the ability to generate cyclic strain on the culture membrane and establish a model of the alveolar air-liquid interface. Next, we utilized three-dimensional finite element analysis modeling to characterize the fluid dynamics within the device and develop a model of the pressure-driven filtration that occurs at the glomerular filtration barrier. Finally, we demonstrate that our model can be used to recapitulate sphingolipid induced kidney injury. Together, our results demonstrate that a multifunctional and modular microphysiological system can be deployed without the use of PDMS. Further, the bio-inert plastic used in our microfluidic device is amenable to various established, high-throughput manufacturing techniques, such as injection molding. As a result, the development plastic organs-on-chips provides an avenue to meet the increasing demand for organ-on-chip technology.
AB - Microphysiological systems, also known as organs-on-chips, are microfluidic devices designed to model human physiology in vitro. Polydimethylsiloxane (PDMS) is the most widely used material for organs-on-chips due to established microfabrication methods, and properties that make it suitable for biological applications such as low cytotoxicity, optical transparency, gas permeability. However, absorption of small molecules and leaching of uncrosslinked oligomers might hinder the adoption of PDMS-based organs-on-chips for drug discovery assays. Here, we have engineered a modular, PDMS-free microphysiological system that is capable of recapitulating biologic barrier functions commonly demonstrated in PDMS-based devices. Our microphysiological system is comprised of a microfluidic chip to house cell cultures and pneumatic microfluidic pumps to drive flow with programmable pressure and shear stress. The modular architecture and programmable pumps enabled us to model multiple in vivo microenvironments. First, we demonstrate the ability to generate cyclic strain on the culture membrane and establish a model of the alveolar air-liquid interface. Next, we utilized three-dimensional finite element analysis modeling to characterize the fluid dynamics within the device and develop a model of the pressure-driven filtration that occurs at the glomerular filtration barrier. Finally, we demonstrate that our model can be used to recapitulate sphingolipid induced kidney injury. Together, our results demonstrate that a multifunctional and modular microphysiological system can be deployed without the use of PDMS. Further, the bio-inert plastic used in our microfluidic device is amenable to various established, high-throughput manufacturing techniques, such as injection molding. As a result, the development plastic organs-on-chips provides an avenue to meet the increasing demand for organ-on-chip technology.
KW - glomerulus-on-chip
KW - lung-on-chip
KW - microfluidic
KW - microphysiological system
KW - organ-on-chip
UR - http://www.scopus.com/inward/record.url?scp=85096642637&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096642637&partnerID=8YFLogxK
U2 - 10.3389/fbioe.2020.581163
DO - 10.3389/fbioe.2020.581163
M3 - Article
AN - SCOPUS:85096642637
VL - 8
JO - Frontiers in Bioengineering and Biotechnology
JF - Frontiers in Bioengineering and Biotechnology
SN - 2296-4185
M1 - 581163
ER -