Development of a new liver-on-chip including BIOMIMESYS® technology for mimicking the liver extracellular matrix: first results and perspectives

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Objective: to develop a new liver-on-chip model that includes a relevant 3D matrix for hepatic cell growth and function with the use of of BIOMIMESYS® Liver hydroscaffold for a physiological 3D hepatocyte culture.

Santé

Development of a new liver-on-chip including BIOMIMESYS®
technology for mimicking the liver extracellular matrix:
first results and perspectives
Introduction
Objective: to develop a new liver-on-chip model that includes a relevant 3D matrix for hepatic cell growth and function
 use of BIOMIMESYS® Liver hydroscaffold for a physiological 3D hepatocyte culture
Results (2)Methods
Conclusion
Victoria Maes1,2, Rachid Jellali2, Marie Lesaffre1, Lilandra Boulais2, Elodie Vandenhaute1, Zied Souguir1, Cécile Legallais2, Nathalie Maubon1
1 HCS Pharma, 250 rue Salvador Allende, Biocentre Fleming Bâtiment A, 59120 Loos, France
2 Sorbonne Universités, Université de Technologie de Compiègne, CNRS, UMR 7338 Biomécanique - Bioingénierie, Compiègne 60205, France
UTC biochip
Cell culture
HepG2/C3A cell line
Patented process
= physiological Hyaluronic Acid (HA)-
based hydroscaffold for 3D cell culture
SEM images of BIOMIMESYS®Design of the microfluidic bioreactor [1]
Phase contrast micrographs (2D culture)
Cellular analyses
Comparison of static condition
(BIOMIMESYS® in 96-well plates) vs
dynamic condition (BIOMIMESYS® in
biochips, with microfluidic flow)
• Viability: Live/Dead assay
• Metabolic activity: glucose and
albumin assays
• Characterization of cells: staining of
neutral lipid and actin
[1] Baudoin et al., 2011 in Biochemical Engineering Journal
Results (1)
 BIOMIMESYS® can be processed into PDMS chips
Current commercial format BIOMIMESYS® within a biochip
Lyophilized (white)
BIOMIMESYS®
hydroscaffold
+ cell culture medium
Rehydrated
(translucent)
BIOMIMESYS®
matrix
 BIOMIMESYS® does not impair the flowrate
 HepG2/C3A grow as spheroids in biochip with
BIOMIMESYS® Liver
HepG2/C3A 24 hours after seeding in biochips (no perfusion yet):
 HepG2/C3A grow better in dynamic (25 µL/min)
vs static conditions in BIOMIMESYS® Liver
Biochip + collagen coating
Cells as islets ( )
Biochip + BIOMIMESYS®
Cells as spheroids ( )
250,000 cells/chip
24h adhesion (A)
+ 72h perfusion (B)
500,000 cells/chip
24h adhesion (C)
+ 72h perfusion (D)
50,000 (G) and 100,000 (H)
cells/hydroscaffold
96h after seeding (static
condition)
 HepG2/C3A remain fully functional in biochips
containing BIOMIMESYS® Liver
40,000 cells/chip
24h adhesion + 5 days (E)
and 12 days (F) perfusion
peristaltic pump
tubing
well
connector
biochip
Liver
=
complex organ
How to model it?
[2] Shang et al., 2019 in Lab on a Chip
or
[2]
Live/dead assay (day 4)
This first study shows that BIOMIMESYS® technology is compatible with
microfluidic systems. In this matrix and under dynamic conditions,
HepG2/C3A cells showed a good viability and functionality.
These results provide the basis for the development of a more complex
microphysiological system to model the liver - with primary cells or
iPSC-derived cells - including a relevant extrcellular matrix.
96-well plate
Biochip
BIOMIMESYS® Liver
D5 D7 D9
96-well plate
BIOMIMESYS® Liver
Biochip
BIOMIMESYS® Liver
Albuminproduction/biochip(ng/h)
Albuminproduction/well(ng/h)
Albumin secretion (ng/h)
D5 D7 D9
96-well plate
Biochip
96-well plate
BIOMIMESYS® Liver
Biochip
BIOMIMESYS® Liver
Glucoseconsumption(µg/h)
125 000 cell/cm2 250 000 cell/cm2
96-well plate
BIOMIMESYS® Liver
Biochip
BIOMIMESYS® Liver
Glucose consumption (µg/h, day 4)
To get this poster,
flash the QR-code
125,000c/cm2250,000c/cm2
A B
C D
E F
HG
Biochip 96-well plate

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