BIOMIMESYS® 3D technology
BIOMIMESYS® is the only 3D culture technology that reproduces the best extracellular matrix with all the desirable biological properties.
The BIOMIMESYS® products are formed by crosslinking reaction of hydrosoluble modified Hyaluronic Acid (HA) and other 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. GAG has the properties to polymerise and thus makes a solid scaffold which keeps the structure of the tissue. Furthermore, this component has different functions, such as binding to water molecules which allow water adsorption and binding to different growth factors.
HCS pharma has found a process to use hyaluronic acid as biopolymer to synthesize their unique 3D cell culture system, allowing them to keep all properties of hyaluronic acid and thus enabling them to reproduce at the best the ECM with all biological properties (same structure, cell adhesion, water stockage, signal reservoir …). Their BIOMIMESYS® technology is the only one on the market with the following 2 properties; having a solid structure and being able to bind to water molecules, thus allowing water adsorption. They named this 3D system “hydroscaffold” after these 2 distinct properties.
Depending on the organ, extracellular matrix components are different and are at various rates, allowing a more or less dense and compact cellular environment (different Elastic Modulus, porosity, …). BIOMIMESYS® 3D technology allows them to reproduce the cell environment of each organ.
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BIOMIMESYS® Adipose tissue
BIOMIMESYS® Adipose tissue is 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 including adipose ECM components, the mechanical properties of HCS pharma’s HA-based scaffold display a Young’s modulus of 0.5 kPa, which is in the same range of adipose tissue ECM. With its 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 the 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 they 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) which constitute the majority of the ECM liver; also plays 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 a significant role 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 its pore size ranging from 60 µm to 130 µm in diameter.
Spheroid: Viability & Growth: Increased Culture Time
Primary human hepatocytes and hepatocarcinoma cell line, such 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 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 a high porosity around 150 ± 30µm.
BIOMIMESYS® Brain provides also enough space for gas, medium and nutrients’ flow circulation in fragile neuronal cell with cell-cell and cells-matrix interactions, along with a mechanical support required for an easy handling of the 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
Seeded neuronal cells could be grown in 3D, under the form of spheroids. They could be maintained for a longer time in BIOMIMESYS® Brain than in 2D. At first intraspheroid neurites could be observed (Day 6, Day 13), and later neurites were also seen between the spheroids (Day 20).
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 has developed the 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 vary depending on the:
● 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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