BIOMIMESYS® Liver

HCS Pharma – Siège de Lille
Biocentre Fleming Bat A
250 rue Salvador Allende
59120 LOOS
BIOMIMESYS®
is a registered trademark
of HCS Pharma
+33 769 999 137
www.biomimesys.com
hello@biomimesys.com
Innovative Hydroscaffolds™ for 3D Cell Culture to better mimic the tissue microenvironment and provide
more predictive tools for drug development and metabolic studies
Other BIOMIMESYS® products available
PRODUCT
BIOMIMESYS® Liver represents a new generation of
mimetic HydroscaffoldS™ for 3D culture of
hepatocyte-like cells. Available in a ready-to-use
format, it enables the culture of hepatocytes and
hepatocyte-like cells under physiological conditions
that are representative of the microenvironment
found in the liver. The highly porous nature of the
Hydroscaffold™ allows the rapid uptake of
nutrients, oxygen, etc. into the cells to create a
reproducible study model for all downstream
analyses used with 3D hepatocyte-like cell culture
(metabolism, toxicity…).
Hyaluronic acid (HA) is a major component of the cells’ extracellular matrix (ECM), biofunctionalized with
liver ECM components (Collagens type I and IV, galactosamine and cell binding domain of Fibronectin),
BIOMIMESYS® Liver Hydroscaffold™ for 3D hepatocytes culture is thus an ideal study model because it is:
Figure 1: SEM picture with artificially stained collagen

59120 LOOS
BIOMIMESYS®
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+33 769 999 137
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 Representative of the hepatocytes’ microenvironment in terms of cell-cell interactions, matrix
composition and cell-matrix interactions
 Highly porous to analyze easily the supernatant (for toxicity and metabolism studies)
 Transparent for direct visualization of cells
 HYALURONIC ACID (HA) + Collagen I & IV system, major component of the adipocyte extracellular
matrix (ECM), where it plays an IMPORTANT ROLE in connective tissue.
 HA-based Hydroscaffolds™ are formed by HA-grafted RGDS and galactosamine + Collagen I & IV
system crosslinking HA with ADH to form reticulated chains.
 High molecular weight HA.
 PHYSICOCHEMICAL FEATURES
o Porosity100-200 µm
o Rheology: Young’s modulus: E= 0.6 ± 0.04kPa
o Swelling ratio = 60 ± 5g/g ?
HEPATOCYTES: HIGHLY POLARIZED AND COMPLEX CELLS
The liver is composed of various cell types, 60% of parenchymal cells or hepatocytes and 40% non-
parenchymal cells (1).
Hepatocytes are highly polarized cells with apical domain representing about 10 to 15% of the cell surface.
This domain is composed of a canalicular network formed between adjacent hepatocytes connected by tight
junctions. These bile ducts are approximately 1µm in diameter and carry bile acid secreted by hepatocytes.
The hepatocytes are highly complex cells providing a variety of functions, the main ones are grouped in the
term “ADMET” (Absorption, Distribution, Metabolism, Excretion, Transport). Hepatocytes control
homeostasis and toxicity of molecules, as they absorb these molecules from blood to metabolize and
redistribute them to various organs. Hepatocytes are also involved in the processing or degradation of
molecules with therapeutic purposes that can generate potentially toxic secondary compounds.
Therefore, during the development phase, about 40% of new drug candidates are discarded due to toxicity
(2). Early detection of this toxicity will not only allow saving money and time but also ethics by limiting the
use of animals.
BIOMIMESYS®
Liver: LIVER EXTRACELLULAR MICROENVIRONMENT
Like most cells, the hepatocyte microenvironment plays an important role in the maintenance of
differentiation, polarization and cellular functions. The extracellular matrix (ECM) is a complex mixture of
functional and structural proteins, glycoproteins and glycosaminoglycans (GAG) organized in a tissue-specific
three-dimensional structure. Hence, many studies have shown the relevance of using de-cellularized organs

59120 LOOS
BIOMIMESYS®
of HCS Pharma
+33 769 999 137
www.biomimesys.com
for hepatocyte culture, recreating a microenvironment favorable to the survival and maintenance of cell
functions (3, 4).
The liver extracellular microenvironment notably contains collagen I, collagen IV and fibronectin which play
a key role in the structuring of the tissue and maintenance of hepatocyte functions (5).
To mimic this bioactive microenvironment, HCS Pharma has developed the world’s first biomimetic
Hydroscaffold™ made of HA, collagen type I and IV, galactosamine and RGDS motif of fibronectin dedicated
to the culture of hepatocytes: BIOMIMESYS® Liver.
Figure 2: Scanning Electron Microscopy (SEM) of BIOMIMESYS® Liver showing collagen fibers, artifically stained in brown (A and C),
decellularized human liver (B, ref 5) and collagen fiber in decellularized rat liver (D, ref 6).
Cell cultures in BIOMIMESYS®Liver were performed with the HepG2 cell line and cryopreserved human
primary hepatocytes.
Seeding was performed following the protocol described in the “first steps” document with the following
cell densities and volumes:
 Primary Hepatocytes: 25 μl with 75,000 cells / gel
 HepG2: 25 µl with 50 000 cells / gel

59120 LOOS
BIOMIMESYS®
of HCS Pharma
+33 769 999 137
www.biomimesys.com
References
1. Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte
sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity,
cell signaling and ADME. Godoy P. et al. Archives Toxicology, 87:1315-1530, 2013
2. Can the pharmaceutical industry reduce attrition rates? Kola I., Landis J. Nat Rev Drug Discov. 3,8:711-
715, 2004
3. Three-dimensional culture of hepatocytes on porcine liver tissue-derived extracellular matrix. Lang
R. et al. Biomaterials. 32,29:7042-52, 2011.
4. Decellularization and cell seeding of whole liver biologic scaffolds composed of extracellular matrix.
Faulk D. et al. J Clin Exp Hepatol. 5, 1:69-80,
5. Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation.
Mazza G. et al. Sci Rep.7;5:13079, 2015.
6. Green tea extract therapy diminishes hepatic fibrosis mediated by dual exposure to carbon
tetrachloride and ethanol: A histopathological study. Safer A. et al., Exp Ther Med. 9(3):787-794,
2015.
PROOF OF CONCEPT
INCREASED CULTURE TIME
MAINTAINED HEPATOCYTE FUNCTIONS
MAINTAINED CYP ACTIVITY & INDUCIBILITY
ALLOWING HEPATOTOXICITY STUDIES
READY TO USE
BIOMIMESYS® is EASY to handle g & READY-TO-USE. Upon receiving the vacuum sealed 96-well plate, open
it (under a hood) and add the cells directly on top of the matrix. Changing the culture medium is easy as
well. To remove medium, simply draw the medium with a pipette between the matrix and the edge of the
well. To refresh the medium, place fresh medium onto the surface of the matrix.

59120 LOOS
BIOMIMESYS®
of HCS Pharma
+33 769 999 137
www.biomimesys.com
96 well plate format
COMPATIBLE TECHNOLOGIES
BIOMIMESYS® Hydroscaffold™ has many properties (translucent, porous, and biodegradable) that make it
ideal for use with numerous downstream applications. The growing cells are easily retrieved from the matrix
by a gentle and rapid procedure, this means that cells cultured in BIOMIMESYS® may be analyzed using all
technologies as shown below.
TRANSPARENT POROUS BIODEGRADABLE SOLID
Microscopy PCRs Flow cytometry Histology
Plate Reader (OD,
fluorescence,
luminescence
Western-Blot
ELISA
10-40µl of cell
suspension
dropped on the
surface of
BIOMIMESYS®
Culture medium
is gently added
on the side of
the well to
obtain qs. 200µl

59120 LOOS
BIOMIMESYS®
of HCS Pharma
+33 769 999 137
www.biomimesys.com
PRICING
BIOMIMESYS®
Liver is sold for RESEARCH USE ONLY.
96-WELL PLATE
**price per plate**
Quantity of 96-well plates 1 ≥ 10 ≥ 100 ≥ 1000
BIO_LIV_96_96_transp
(96 well plate with 96 Hydroscaffolds™)
BIO_LIV_96_24_transp
Quantity of 96-well *BLACK*plates 1 ≥ 10 ≥ 100 ≥ 1000
BIO_LIV_96_96_black
BIO_LIV_96_96_black
BIO_LIV_384-384_black
Contact Information
HCS Pharma
http://www.biomimesys.com

BIOMIMESYS® Liver

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