The value of marine products
is not limited to food, and they can have even greater value if used adequately.
Our research uses the latest physiology, biochemistry, and biotechnology to
create value in the fisheries and aquaculture industries. Here, we introduce the
research on collagen obtained from fish processing byproducts.
Stuegeon aquaculture: Many byproducts are left unused
The aquaculture of sturgeons, which produces high-quality caviar,
is expected to be highly profitable. However, most of the fish body (called byproducts)
after caviar processing is discarded and is very wasteful as only a small part
of the meat is used. Thus, it is important to develop uses of the byproducts byreducing the parts to be discarded (zero emission).
Collagen is extracted from byproductsto generate
materials for tissue engineering, health foods，and cosmetics. The amount
obtained varies greatly depending on the body part and extraction method.
Collagen fibril -material development for tissue engineering-
The collagen molecule is a
type of protein. It is made up of three spiral peptide-bond chains of amino
acids and is a string with a diameter of 1.5 nm and a length of 300 nm.
A thick fibrous bundle of collagen
fibrils is called a collagen fiber bundle. Collagen fibrils and fiber bundles
are distributed among various tissues and organs in our body, supporting the
body three-dimensionally. Thus, they play the role of a reinforcing bar in a
reinforced concrete building. The space between the collagen fibrils and fiber
bundles is filled with proteoglycans, which act as concrete in a reinforced
concrete building. A proteoglycan contains a large number of sugar chains bound
to the core protein and has high water retention. The complex of collagen and
proteoglycan, called the extracellular matrix, plays an important role in life
support by acting as a cell scaffold and storing signal transmitters for cells
to regulate their activity.
An artificial scaffold (such as collagen) is necessary for creating
artificial tissues with cultured cells in biotechnology. Upon binding to a
scaffold, cells acquire various information from the scaffold to proliferate or
differentiate into each tissue. With an appropriate scaffold, the proliferation
or differentiation of cells can be induced as intended.
On the other hand, cells with
a poor scaffold die by themselves (apoptosis). An appropriate scaffold depends
on the type of tissues to be created. As the extracellular matrix structure
found in the tissues of our body differs from tissue to tissue, a custom-made
scaffold is needed for each type of tissue to be created.
Because the tissues of living
organisms have a three-dimensional structure, they do not form with a flat
scaffold. A custom-made scaffold with a three-dimensional structure is needed for
each tissue, which requires a suitable scaffold material.
Tissue engineering and regenerative medicine using sturgeon collagen
Tissue engineering combines stem cells, three-dimensional cell scaffold materials，and cytokines to create artificial tissues. In regenerative
medicine for bone diseases, for example, the stem cells collected from a patient
are proliferated by adding a scaffold (collagen) with an appropriate
three-dimensional structure and differentiation-inducing factors, and then they
are differentiated into osteoblasts and cartilage cells. Once the artificial
bone tissue grows to the size required for treatment, it is transplanted to the
disease site of the patient.
Our laboratory is conducting research on the application of sturgeon collagen to cell scaffold materials fortissue engineering.
The artificial scaffold of fish collagen has many advantages.
Suitable for material synthesis due to its high fibrogenic ability
Fibrotic material has a high
affinity for cells
→Stem cells adhere well to the
scaffold and easily fuse with the surrounding tissues after transplantation.
Free from common infectious
diseases with humans
(In Europe, all scaffolds have been switched to fish collagen)
Collagen is used in four forms
1. Fibril: the fiber of
The form of collagen found inside the body of animals. The molecules
are arranged regularly to form a fiber.
It serves as a cell scaffold,creating
a three-dimensional structure of the tissue.
The price of collagen varies as the manufacturing method and
cost are different depending on the form of collagen. The most expensive collagens
are the molecules and the fibrils composed of molecules. Highly purified
collagen molecules for cell culture are worth approximately 150,000 yen per
gram. More than four grams of collagen can be obtained from the swim bladder of sturgeon (2 kg), which is worth over 600,000 yen. This is approximately
the same value as caviar from a female (20 kg).
(The price of caviar varies depending on the quality, but it is
calculated at 300 yen per gram, which is a medium quality caviar).
Large amounts of collagen can be obtained from byproducts of sturgeons
Because a large amount of
collagen can be obtained from theskin and swim bladder their industrialization is possible.
Type IIcollagen can be obtained from thenotochord. Type IIcollagen is contained in
special tissues, such as the cartilage, and is a valuable collagen with a small
amount distributed on the market. The notochordis a
tissue unique to the ancient fish Acipenseridae, which normally degenerates in other
Type I collagen is extracted from the swim bladder of sturgeons
Collagen molecules are
extracted fromeach part of an animal. To be used as a collagen material for
medical use, it must be thoroughly purified and have no impurities. Purified
collagen molecules need to be returned to fibrils for use as cell culture
scaffolds. This requires establishing the conditions under which the regular
fibrils (fibrils that can efficiently induce cell proliferation and
differentiation) are produced. On satisfying these requirements, we aim to
streamline processing and bring it to the world as an industrial product.
Making fibrils from the swim bladder collagen of sturgeons
Collagen from the swim bladder of sturgeons exhibits special
properties that are different from mammalian collagen. The extracted collagen
molecules dissolve well in an acidic solution (left), but when neutralized with
a buffer solution, they form fibrils and become cloudy and white (right).
This graph shows the change in the cloudiness measured with a
spectrophotometer. As you can see, the swim bladder collagen (red line) becomes
cloudy more quickly (= fibril formation progresses) than the porcine collagen
Zhang et al., 2014, Food Chemistry
These are scanning electron
micrographs of the fibrils prepared as mentioned above. As you can see, fibers
of various thicknesses are formed. Porcine collagen can only make much finer
fibrils. When used as cell scaffolds, it is highly advantageous for collagen
fibrils to be able to quickly produce various forms. This is because cells can
recognize the thickness and orientation of the collagen fibrils in scaffolds
and react in various ways. If the thickness and orientation of the collagen
fibrils of the swim bladder can be controlled, it may be possible to control the
proliferation and differentiation of cells.
The development of coating technology of collagen fibrils enables inventive research
We have developed a technology
to coat cell culture dishes with the collagen fibrils of sturgeons swim bladders.
Scanning electron micrographs of a culture dish coated with (B) collagen
molecules，(C) thin fibrils，and (D) thick fibrils
E, H, and K are polarized light micrographs of mouse osteoblast
progenitor cells cultured in each dish. Each shows a characteristic cell
morphology, and the cells, especially in K, extend in one direction along the
traveling direction of the fibrils (arrow in K). Although not shown in the
figure, cell proliferation and differentiation also differ greatly depending on
the type of coating. Such coating is not possible with porcine collagen. This
technology has made it possible to develop inventive research, such as investigating
the reaction of cells to collagen in detail.
We will further develop this technology, aiming to synthesize
three-dimensional cell scaffold materials in the future.
By the way, did you
notice the references of the research introduced here, such as “Zhang et al., 2014, Food
Chemistry” and “Moroi
et al., 2019, Materials Science and Engineering: C”? These mean that the figures were taken from academic papers
published in academic journals. Mr. Zhang and Mr. Moroi are graduates of our
laboratory, and the research results introduced here are some of the results
they obtained while they were enrolled in the Master’s program at the graduate
If you are a science student,
you will conduct graduation research in your fourth year, and Master’s thesis
research and doctoral dissertation research will be conducted if you go on to
graduate school. So, the results of your research may also be published in
The research you conduct in
the laboratory of the university will contribute to the development of science
and become the common property of all humankind. It may also be used directly
for product development, making a profit.
We hope you enjoy your
research and get good results.