Iwai North America Inc.

541 Taylor Way Suite# 4
 San Carlos, CA 94070
 Phone : (650) 486-1541
Fax : (650) 394-8638
 Open weekdays 9 AM-6 PM (PST)
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BioMIMESYS® is an Organ specific Extracellular Matrix (ECM) formed by crosslinking reaction of hydrosoluble modified Hyaluronic Acid (HA) and other ECM components (collagens, fibronectin, etc.) with ADH (Adipic acid dihydrazide), to create a "Hydroscaffold" 3D cell culture system.
2D cell culture is not a true reflection of the physiological cell environment. In a real body, cells grow in 3D, connecting to other cells and the extracellular matrix (ECM) to build tissues and organs. Therefore, 3D cell culture can better mimic the original tissue’s specific characteristics. Some of the processes studied in 2D culture such as gene expressionapoptosis, and, importantly, drug uptake and toxicity may not be directly transferable to in vivo experiments. 
The Importance of ECM

ECM has greatly determines cell activity and viability (1) by:

    • Maintaining the structure of tissues and organs

    • Defining microenvironment for cells

    • Determining cell behavior and function

Changes dynamically through development and function (healthy - diseased). And, notably, ECM composition is organ-specific.

Side Note: Components of ECM

 ECM consists of interlocking mesh of   fibrous proteins and glycosaminoglycans

 Proteins 

    • Collagen – structural support
    • Elastin – provide elasticity 

 Glycosaminoglycans

    • Proteoglycans(GAG) – hydration
    • Polysaccharides (Hyaluronic acid) -                  load bearer, hydration

 Glycoproteins

    • Fibronectin – connect cell with collagen       fibers, movement of cells
    • Laminin – basal laminae, cell adhesion

 Linker proteins such as nidogen and entactin,   which connect collagens with other protein   components.

The ideal ECM for research is decellularized organs, but the cost, reproducibility, and scalability make it impractical for continuous use. The following characteristics of the ECM that Biomimesys provides makes it the best alternative.
1) BIOMIMESYS is a physiological hydroscaffold to mimic tissue-specific ECM 

• BIOMIMESYS® scaffold possesses a similar structure and mechanical property in hydrated stage to natural organs (Fig.2)

• Made of high molecular weight Hyaluronic acid (1.6 MDa), adipic acid dihydrazide crosslinker, undenatured collagen and other ECM. 

• Tissue/organ-specific scaffold available and customizable. Various ECM compositions and physical properties are available and customizable to mimic healthy and diseased tissues. 

2) High porosity for greater diffusion

• The porous nature of the scaffold provides greater diffusion of oxygen and nutrients for better viability and greatly decreases the formation of necrotic core, often seen in other spherical 3D models.

• The abundance of metabolic enzyme activities and normal cellular polarity makes it ideal for in vitro models

Side Note:

In addition to oxygen tension, cell behavior in 3D cultures is regulated by a variety of other biophysical and biochemical properties of the microenvironment including CO2 concentration, availability and diffusion properties of nutrients and waste products, matrix rigidity and the presence of matrix-binding factors in the culture medium. (Fig. 3)  

3) Many potential applications and Cells tested

• Microscopy (Immunofluorescence, histology)
• Plate readers (OD, fluorescence & luminescence)
• Protein and RNA extraction, PCR, Western-Blot

References:

1. Lu P, Weaver VM, Werb Z. The extracellular matrix: A dynamic niche in cancer progression. J Cell Biol. 2012 Feb 20;196(4):395.

2.  Wang L, Johnson JA, Zhang Q, Beahm EK. Combining decellularized human adipose tissue extracellular matrix and adipose-derived stem cells for adipose tissue engineering. Acta Biomater. 2013 Nov;9(11):8921–31. 

3.  Colom A, Galgoczy R, Almendros I, Xaubet A, Farre R, Alcaraz J. Oxygen diffusion and consumption in extracellular matrix gels: implications for designing three-dimensional cultures. J Biomed Mater Res A. 2014 Aug;102(8):2776–84. 

4. McMurtrey RJ. Analytic Models of Oxygen and Nutrient Diffusion, Metabolism Dynamics, and Architecture Optimization in Three-Dimensional Tissue Constructs with Applications and Insights in Cerebral Organoids. Tissue Eng Part C Methods. 2016 Mar 1;22(3):221–49. 

5. Al-Ani A, Toms D, Kondro D, Thundathil J, Yu Y, Ungrin M. Oxygenation in cell culture: Critical parameters for reproducibility are routinely not reported. PloS One. 2018;13(10):e0204269.
Why 3D Cell Culture?
Characteristics of Hyaluronic Acid

• Main component of the interstitial gel.
• Found on the inner surface of the cell membrane and translocate out of the cell during biosynthesis.
• Known to be less toxic and cause less allergic reaction. Can be used for in vivo experiment model! 
• Absorb significant amount of water to allowing tissues to swell thus enabling it to resist compression.  
• Acts as an environmental cue that regulates cell behavior during embryonic development, healing processes, inflammation, and tumor development. 
• Interacts with a specific transmembrane receptor, CD44 (Ref: Lodish et al, Peach 1993).
Ideal 3D Models - Why BIOMIMESYS
Fig.1: Mechanisms of ECM function.
Lu et al. J Cell Biol. 196, 395-206, 2012

Cells Tested

Cell Lines

Human brain metastasis SA87
Human breast adenocarcinoma MCF-7
Human breast carcinoma CAL-51
Human cervix adenocarcinoma HeLa
Human colorectal adenocarcinoma DlD-1 / HT29 / Caco-2
Human glioblastoma CB109 / CB74 / CB191
Human liver hepatocellular carcinoma HepG2
Human liver hepatoma PLC / PRF-5
Human lung carcinoma NCI-H460
Human osteosarcoma SaOs
Human ovarian carcinoma IGROV-1
Human pancreas carcinoma PANC-1
Human prostate cancer PC3
Human hepatic stellate LX2
Normal human colon fibroblast CCD18-co
Normal mouse preadipocytes 3T3-L1 / 3T3-F442A

Primary Cells

Human white pre-adipocyte subcutaneous HWP cryopreserved
Human hepatocytes HH cryopreserved

Stem Cells

Hematopoietic CD34+
Human induced pluripotent stem cells hiPS
Pricing

BIOMIMESYS® is sold for RESEARCH USE ONLY.