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

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.

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

  1. 1. 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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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.

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