BIOMIMESYS® 3D technology
The BIOMIMESYS® products are formed by crosslinking reaction of hydrosoluble modified Hyaluronic Acid (HA) and others extracellular matrix (ECM) components (collagens, fibronectin…) with ADH (Adipic acid dihydrazide), to form the extra-cellular matrix.
In ECM, Hyaluronic acid (HA) is a key player which has different properties. This GAG has the properties to polymerise and thus made a solid scaffold which keeps the structure of the tissue. Furthermore, this component has different functions that binds to water molecules which allow water adsorption and that could bind different growth factors.
The fact that we have found a process to used hyaluronic acid as biopolymer to synthesis our 3D cell culture system allows us to keep all properties of hyaluronic acid and thus to reproduce at the best the ECM with all biological properties (same structure, cell adhesion, water stockage, signal reservoir …). Our BIOMIMESYS® technology is the only one on the market with these 2 properties, which are to be solid and to bind to water molecules and thus to allow water adsorption. It is because of these 2 properties, we called this 3D system : hydroscaffold.
Depending on the organ, extracellular matrix components are different and at various rates, allowing a more or less dense and compact cellular environment (different Elastic Modulus, porosity, …). BIOMIMESYS® 3D technology allows us to reproduce the cell environment of each organ.
(BIOMIMESYS®’s website is here)
BIOMIMESYS® Adipose tissue
BIOMIMESYS® Adipose tissue a biofunctionalized Hyaluronic Acid (HA) hydroscaffold with components of adipose tissue extracellular matrix: collagen I, collagen VI and the cell binding domain of fibronectin (RGDS). BIOMIMESYS® Adipose tissue provides an inductive microenvironment and permits a complete differentiation of preadipocytes which are organized in an in vivo-like round shape and are dose-responsive to well-known modulators of adipocyte lipogenesis and lipolysis.
In addition to include adipose ECM components, the mechanical properties of our HA-based scaffold display a Young’s modulus of 0.5 kPa, which is in the same range of adipose tissue ECM. With a pore size ranging from 70 to 170 µm, BIOMIMESYS® Adipose tissue provides also enough space for medium and nutrients flow circulation, maturation of large fragile primary adipocytes with cell-cell and cells-matrix interactions, along with a mechanical support required for an easy handling of hydroscaffold.
BIOMIMESYS® Adipose tissue increases marker genes expression of adipogenesis, in preadipocytes :
- – early genes as FABP4 (fatty acid binding protein) :
– late genes as GLUT4 (Glucose Transporter) :
With better differentiation, adipocytes show better lipid accumulation when adipocytes are grown in BIOMIMESYS® Adipose tissue compared to 2D culture :
BIOMIMESYS® Adipose Tissue – Technical Data Sheet
BIOMIMESYS® Adipose Tissue – Poster
BIOMIMESYS® Adipose Tissue – Publication
BIOMIMESYS® Liver hydroscaffold is made of RGDS and galactosamine-grafted Hyaluronic acid, Adipic acid dihydrazide crosslinker and extracellular matrix (ECM) proteins (collagen type I and collagen type IV) to mimic liver-ECM composition. The SEM image shows the biomimetic structure of the BIOMEMISYS® Liver hydroscaffold with collagen chains.
A factor which greatly determines cell activity and viability is the extracellular matrix (ECM). Liver cells are organized and maintained by a complex extracellular microarchitecture. ECM compounds play a tremendous role in liver function regulation. Collagens, glycoproteins and glycosaminoglycans (GAG) constitute the majority of the ECM liver; also play important roles in cell physiology.
BIOMIMESYS® Liver hydroscaffold
BIOMIMESYS®Liver (on the right) and ECM from decellularized liver (on the left)
Hyaluronic acid (HA) has significant roles in the physical properties of liver tissue. HA sequesters water to maintain hydration of the ECM and also provides lubrication to enable cell motility and migration. HA is important during new liver tissue formation to promote activity of proliferating cells. These properties and its ability to avoid immune reactions upon transplantation make HA a suitable substrate for 3D cell culture and use for in vivo treatments.
The mechanical properties of BIOMIMESYS® Liver hydroscaffold display a Young’s modulus of 0.6 kPa, which is in the same range of Liver ECM. The hydroscaffold is porous with pores size ranging from 60 µm to 130 µm diameter.
Spheroid: Viability & Growth: Increase Culture Time
Primary human hepatocytes and hepatocarcinoma cell line, as HepG2, remain viable for longer time in culture compared to 2D. Furthermore, primary human hepatocytes keep their metabolic activity for longer time in culture compared to 2D, even in sandwich culture.
Maintains hepatocytes functions: Biliary Canaliculi Formation – HepG2
Formation of canaliculi network with Actin and MRP2 colocalization
Maintains metabolic activities: Cryopreserved human hepatocytes
20 to 30 times more albumin is secreted in BIOMIMESYS®Liver than in 2D. Basal CYP activity was analysed after 7 days of culture in 2D or in 3D.
Basal CYP activities are higher using BIOMIMESYS® Liver compared to 2D culture in sandwich.
BIOMIMESYS® Liver – Technical Data Sheet
BIOMIMESYS® Liver – Poster
BIOMIMESYS® Brain is a unique ready to use biofunctionalized Hyaluronic Acid (HA) hydroscaffold suitable for neuronal cells culture. BIOMIMESYS® Brain is carried out by double crosslinking reaction of components of brain extracellular matrix: collagen I and IV, cell binding domain of fibronectin (RGDS), cationic bioplolymer and Hyaluronic acid. BIOMIMESYS® Brain provides an inductive microenvironment and permits a long term culture of neuronal cell.
In addition to include brain ECM components, the mechanical properties of our biofunctionalized Hyaluronic Acid based hydroscaffold display a low Young’s modulus of 0.1 kPa (soft hydroscaffold), which is in the same range of brain ECM. Always with the aim of better mimicking the structural properties of brain, BIOMIMESYS® Brain is made up of 80% empty volume and with à high porosity around 150 ± 30µm.
BIOMIMESYS® Brain provides also enough space for gas, medium and nutrients flow circulation of fragile neuronal cell with cell-cell and cells-matrix interactions, along with a mechanical support required for an easy handling of hydroscaffold.
Pictures of dopaminergic neurons (Luhmes cells) 6, 13 and 20 days after seeding in BIOMIMESYS® Brain. In green: beta3-tubulin, in blue: nuclei stained with Hoechst; scale bar = 200 µm
BIOMIMESYS® Brain – Technical Data Sheet
Extracellular matrix (ECM) is a complex viscoelastic system composed of various distinct components (GAG, Collagen…) that are often organized into a fibrillar microstructure.
The physicochemical properties (composition and architecture) of the ECM play a critical role in regulating important cellular functions such as spreading, migration, proliferation, and differentiation.
To better mimic the tumor microenvironment, HCS Pharma develops BIOMIMESYS® Oncology , a double interpenetrating network (IPN) hydroscaffold based on Hyaluronic acid (HA) and type I collagen crosslinked with Adipic acid dihydrazid (ADH).
SEM observation of a BIOMIMESYS® Oncology: section magnification
HTC-116 Cells – Day 30 – DAPI (blue) MitoTracker (Yellow) Edu (Green) merged colors – 10 deep layers view
Spheroid growth, Viability, Cell proliferation
BIOMIMESYS® Oncology hydroscaffold provides cell binding sites with CD44 and RHAMM allowing cell-matrix and cell-cell interactions.
Cancer cells growing in BIOMIMESYS® Oncology hydrscaffold proliferate and aggregate to form spheroids from the 5th day of culture. The size and formation of the spheroids varies as a function of:
- ●Seeding density
- ●Length of culture
- ●Cell type
The cells can be cultured for at least 28 days.
Colorectal cancer cells grown in BIOMIMESYS® Oncology
HT-29 Cells – Day 7 – DAPI (blue) MitoTracker (Yellow)
HTC-116 Cells – Day 15 – DAPI (blue) MitoTracker (Yellow) Edu (Green)
HTC-116 Cells – Day 30 – DAPI (blue) MitoTracker (Yellow) Edu (Green) and merged colors
BIOMIMESYS® Oncology – Technical Data Sheet
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