A thermoplastic microfluidic microphysiological system to recapitulate hepatic function and multi-cellular interactions.

Authors:
Shyam Sundhar Bale
Shyam Sundhar Bale
Rensselaer Polytechnic Institute
United States
Rebecca Thompson
Rebecca Thompson
University of Toledo
United States
Hesham Azizgolshani
Hesham Azizgolshani
Department of Mechanical Engineering
Mingjian Lu
Mingjian Lu
Institute for Diabetes
Orlando | United States
James Gosset
James Gosset
Leiden University
Netherlands

Biotechnol Bioeng 2019 Apr 9. Epub 2019 Apr 9.

Draper, 555 Technology Square, Cambridge, MA.

Hepatic in vitro platforms ranging from multi-well cultures to bioreactors and microscale systems have been developed as tools to recapitulate cellular function and responses to aid in drug screening and disease model development. Recent developments in microfabrication techniques and cellular materials enabled fabrication of next-generation, advanced microphysiological systems (MPSs) that aim to capture the cellular complexity and dynamic nature of the organ presenting highly controlled extracellular cues to cells in a physiologically relevant context. Historically, MPSs have heavily relied on elastomeric materials in their manufacture, with unfavorable material characteristics ( such as lack of structural rigidity) limiting their use in high-throughput systems. Herein, we aim to create a microfluidic bilayer model (microfluidic MPS) using thermoplastic materials to allow hepatic cell stabilization and culture, retaining hepatic functional phenotype and capturing cellular interactions. The microfluidic MPS consists of two overlapping microfluidic channels separated by a porous tissue-culture membrane that acts as a surface for cellular attachment and nutrient exchange; and an oxygen permeable material to stabilize and sustain primary human hepatocyte (PHH) culture. Within the microfluidic MPS, PHHs are cultured in the top channel in a collagen sandwich gel format with media exchange accomplished through the bottom channel. We demonstrate PHH culture for 7 days, exhibiting measures of hepatocyte stabilization, secretory and metabolic functions. In addition, the microfluidic MPS dimensions provide a reduced media-to-cell ratio in comparison with multi-well systems, minimizing dilution and enabling capture of cellular interactions and responses in a hepatocyte-Kupffer co-culture model under an inflammatory stimulus. Utilization of thermoplastic materials in the model and ability to incorporate multiple hepatic cells within the system is our initial step towards the development of a thermoplastic-based high-throughput microfluidic MPS platform for hepatic culture. We envision the platform to find utility in development and interrogation of disease models of the liver, cellular interactions and therapeutic responses. This article is protected by copyright. All rights reserved.

Download full-text PDF

Source
http://dx.doi.org/10.1002/bit.26986DOI Listing
April 2019
1 Read

Publication Analysis

Top Keywords

microfluidic mps
20
cellular interactions
12
capture cellular
8
phh culture
8
thermoplastic materials
8
microfluidic
7
cellular
7
hepatic
6
mps
5
hepatic functional
4
functional phenotype
4
model ability
4
stabilization culture
4
tissue-culture membrane
4
ability incorporate
4
phenotype capturing
4
culture retaining
4
retaining hepatic
4
capturing cellular
4
channels separated
4

Similar Publications