Abbreviations used in the paper:
CCK-8: Cell counting kit-8 assay
Fa: fraction absorbed
FBS: fetal bovine serum
FITC: fluorescein isothiocyanate
GO: gene ontology
H&E: Hematoxylin and eosin
HBSS: Hank’s Balanced Salt Solution
KEGG: Kyoto Encyclopedia of Genes and Genomes
Papp: apparent permeability coefficient
PBS: phosphate-buffered saline
PC: polycarbonate
PET: polyethylene terephthalate
PFA: paraformaldehyde
PS: penicillin/streptomycin
RNA-Seq: RNA sequencing
SEM: scanning electron microscopy
TEER: transepithelial electrical resistance
Abstract:
Organ-on-a-chip technology has shown great potential in disease modeling
and drug evaluation. However, traditional organ-on-a-chip devices are
mostly pump-dependent with low throughput, which makes it difficult to
leverage their advantages. In this
study, we have developed a generic, pump-free organ-on-a-chip platform
consisting of a 32-unit chip and an adjustable rocker, facilitating
high-throughput dynamic cell culture with straightforward operation. By
utilizing the rocker to induce periodic fluid forces, we can achieve
fluidic conditions similar to those obtained with traditional pump-based
systems. Through constructing a gut-on-a-chip model, we observed
remarkable enhancements in the expression of barrier-associated proteins
and the spatial distribution of differentiated intestinal cells compared
to static culture. Furthermore, RNA sequencing analysis unveiled
enriched pathways associated with cell proliferation, lipid transport
and drug metabolism, indicating the ability of the platform to mimic
critical physiological processes. Additionally,
we tested seven drugs which
represent a range of high, medium, and low in vivo permeability
using this model and found a strong correlation between their
Papp values and human Fa, indicating reliable and
predictive simulation outcomes for drug absorption. Our findings
highlight the potential of this pump-free organ-on-a-chip platform as a
valuable tool for advancing drug development and enabling personalized
medicine.