Dataset Information

Gravity-Based Flow Efficient Perfusion Culture System for Spheroids Mimicking Liver Inflammation.

ABSTRACT: The spheroid culture system provides an efficient method to emulate organ-specific pathophysiology, overcoming the traditional two-dimensional (2D) cell culture limitations. The intervention of microfluidics in the spheroid culture platform has the potential to enhance the capacity of in vitro microphysiological tissues for disease modeling. Conventionally, spheroid culture is carried out in static conditions, making the media nutrient-deficient around the spheroid periphery. The current approach tries to enhance the capacity of the spheroid culture platform by integrating the perfusion channel for dynamic culture conditions. A pro-inflammatory hepatic model was emulated using a coculture of HepG2 cell line, fibroblasts, and endothelial cells for validating the spheroid culture plate with a perfusable channel across the spheroid well. Enhanced proliferation and metabolic capacity of the microphysiological model were observed and further validated by metabolic assays. A comparative analysis of static and dynamic conditions validated the advantage of spheroid culture with dynamic media flow. Hepatic spheroids were found to have improved proliferation in dynamic flow conditions as compared to the static culture platform. The perfusable culture system for spheroids is more physiologically relevant as compared to the static spheroid culture system for disease and drug analysis.

SUBMITTER: Kim YS

PROVIDER: S-EPMC8533112 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Gravity-Based Flow Efficient Perfusion Culture System for Spheroids Mimicking Liver Inflammation.

Kim Young-Su YS Asif Arun A Chethikkattuveli Salih Abdul Rahim AR Lee Jae-Wook JW Hyun Ki-Nam KN Choi Kyung-Hyun KH

Biomedicines 20211001 10

The spheroid culture system provides an efficient method to emulate organ-specific pathophysiology, overcoming the traditional two-dimensional (2D) cell culture limitations. The intervention of microfluidics in the spheroid culture platform has the potential to enhance the capacity of in vitro microphysiological tissues for disease modeling. Conventionally, spheroid culture is carried out in static conditions, making the media nutrient-deficient around the spheroid periphery. The current approac ...[more]

PMID: 34680487

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Project description:Microphysiological systems, also known as body-on-a-chips, are promising "human surrogates" that may be used to evaluate potential human response to drugs in preclinical drug development. Various microfluidics-based platforms have been proposed to interconnect different organ models and provide perfusion in mimicking the blood circulation. We have previously developed a pumpless platform that combines gravity-driven fluid flow and a rocking motion to create reciprocating flow between reservoirs for recirculation. Such platform allows design of self-contained and highly integrated systems that are relatively easy and cost-effective to construct and maintain. To integrate vasculature and other shear stress-sensitive tissues (e.g. lung and kidney) into pumpless body-on-a-chips, we propose "UniChip" fluid network design, which transforms reciprocating flow input into unidirectional perfusion in the channel(s) of interest by utilizing supporting channels and passive valves. The design enables unidirectional organ perfusion with recirculation on the pumpless platform and provides an effective backflow-proof mechanism. To demonstrate principles of UniChip design, we created a demonstration chip with a single straight channel as a simple example of the organ perfusion network. A BiChip providing bidirectional perfusion was used for comparison. Computational and experimental fluid dynamic characterization of the UniChip confirmed continuous unidirectional flow in the perfusion channel and the backflow-proof mechanism. Vascular endothelial cells cultured on UniChips for 5 d showed changes matching cell responses to unidirectional laminar flows. Those include cell elongation and alignment to the flow direction, continuous network of VE-cadherin at cell borders, realignment of F-actin and suppressed cell proliferation. Cells on BiChips manifested distinct responses that are close to responses to oscillatory flows, where cells remain a polygonal shape with intermittent VE-cadherin networks and few F-actin realignment. These results demonstrate that microfluidic devices of UniChip design provide recirculating unidirectional perfusion suitable for long-term culture of shear stress-sensitive tissues. This is the first time a gravity-drive flow system has achieved continuous unidirectional perfusion with recirculation. The inherent backflow-proof mechanism allows hassle-free long-term operation of body-on-a-chips. Overall, our UniChip design provides a reliable and cost-effective solution for the integration of vasculature and other shear stress-sensitive tissues into pumpless recirculating body-on-a-chips, which can expedite the development and widespread application of moderately high-throughput, high-content microphysiological systems.

Dataset Information

Gravity-Based Flow Efficient Perfusion Culture System for Spheroids Mimicking Liver Inflammation.

Publications

Gravity-Based Flow Efficient Perfusion Culture System for Spheroids Mimicking Liver Inflammation.

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