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This artificial cornea, once implanted, acts
as a scaffold for cornea cells and nerves to grow in. |
Now scientific research seeks to help the body rebuild itself.
"The research is in the area of regenerative medicine and particularly
we’re interested in tissue engineering," says Dr. May
Griffith, a cell biologist with the Ottawa Eye Institute.
Researchers are using polymers to create a structure that cells
can easily grow in and regenerate tissue. "Polymer is just
a very very big molecule, which is nothing new,” Dr. David
Carlsson says, an Emeritus researcher with the National Research
Council. “Nature has been making these things for millions
and millions of years."
Natural and synthetic
Synthetic polymers include plastics, ranging from toothbrushes
to cell phones. Cushions and Styrofoam are examples of polymer foams.
Polymers also occur naturally in the body, in collagen and starch.
Natural polymers are useful for tissue engineering because they’re
biodegradable.
Body parts
The World Health Organization estimates that 10 million people
are in need of cornea transplants to prevent blindness. The cornea
is the transparent layer over the front of the eye. It directly
covers the iris, the coloured part of the eye.
The cornea becomes cloudy with age, disease or injury. "It’s
responsible for about 80 per cent of the light transmission into
the eye," Griffith says. "So that’s why if it’s
cloudy the vision is obscured."
Seeking sight
Dr. Griffith and her team created a polymer cornea implant that
helps patients generate a new cornea. It looks much like a contact
lens.
"So what we do is use either natural polymers, like collagen
or a mixture of natural and synthetic polymers, mix them up, put
them into a mold, then mold them into the shape of a cornea. And
so these are just transplanted into animals," Griffith says.
The goal is to make an implant that closely resembles a human
cornea. "We aim for the same properties, so you know [the]
same transparency, same water content, and then to that we add …bioactive
peptides…that encourages nerve growth," Griffith says.
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The cells inside this test tube will be used
to create a synthetic mold for testing. |
"But you know whatever you put into it will depend on what
condition you’re trying to treat."
The transplants have been tested in mice, rats and rabbits, Griffith
says.
The treatment for corneal disease is transplantation from human
tissue donation. But Griffith hopes that some of her transplant
models will be available to people in the next few years. "There
are some that are almost ready to go into humans right now; we just
probably need to get through all that paper work."
A step further
Joint replacement is one of the top three areas where treatment
is most needed, according to the Canadian Institutes of Health Research.
Knee problems are very common, Carlsson says, because cartilage
in the knee gets worn out with age. "It will start to break
down, finally you’ll get bone to bone contact and you get
intense pain. So people cannot walk properly and they lose mobility,"
he says.
The treatment for a knee replacement now is basically to replace
this very complex joint with a mechanical hinge. "It’s
still a prosthesis— an artificial device going into your body,
nothing like the original tissue," Carlsson says.
'It’s known already
that the body can regenerate, meaning repair, rebuild, a lot
of parts of your body if you could only find out how to help
the body do that.' |
"It’s known already that the body can regenerate, meaning
repair, rebuild, a lot of parts of your body if you could only find
out how to help the body do that," Carlsson says. "But
could you get the cells in your knee which can build this material
we call cartilage…and restore it just the way it was?"
The answer isn’t so simple. "Theoretically you can
do it. Technically it’s a huge problem," says Dr. Carlsson.
The trick is to create the right environment for the cells to grow
in. The cells you’re working with will depend on the kind
of tissue you wantto grow, and different cells thrive in different
environments.
Dr. Victoria Nawaby, of the National Research Council, uses gases
to create certain structures with polymers. "We’re working
on a corn based polymer, a polymer that is obtained from a natural
resource rather than a petrochemical base," she says. A natural
based polymer is more compatible with the human body and can be
used to create a scaffold to grow cells on.
Building a dream home
An ideal scaffold for cell growth is like an apartment complex
with doors connecting each separate unit. The cells would be placed
in each apartment and begin to multiply and connect with their neighbouring
cells to eventually form a tissue. But the original scaffold will
eventually disappear if it’s made of biodegradable material.
"Now [if] this apartment complex is biodegradable eventually
these guys will use this as food and they will grow enough and become
a healthy tissue and they take over on their own," Nawaby says.
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Dr. David Carlsson displays artificial corneas
made from polymer material. |
"My area is to design this apartment complex," Nawaby
says. This complex is called a polymeric cellular morphology or
foam. "An example of a foam is a Styrofoam cup. But the cell
size in that is very large, you break it and you can literally see
the cavities in between," she says.
The foams Nawaby creates cannot be seen with the naked eye. "What
we use is a scanning electron microscope and the magnification is
very high. We can go up to 30, 000 in terms of magnification,"
she says.
"So far we’re playing around with ‘can you do
this from corn-based polymers?’ ‘Can you create this
apartment complex with open cavities?’" Nawaby says.
Nawaby has been testing CO2 and nitrogen with the polymers. The
first step is to dissolve the gas. Secondly, wait until the gas
is completely dispersed everywhere and it has reached equilibrium,
a condition in which everything is balanced. This could take 24
or 48 hours depending on the gas. The last step is to quickly drop
the pressure or raise the temperature to disrupt the equilibrium,
Nawaby says.
"Those little cavities get created because of this sudden
thermodynamic change."
Think of opening a soda bottle and watching all the bubbles race
to the surface. It is these bubbles that would lock in place and
form the cavities or holes that would become the home for cells.
Ideally all the cavities in the scaffold should be the same size.
"It crystallizes or the chains start to order themselves and
it sometimes prevents you from having a very uniform apartment complex…you
may have one very big…apartment and then a small one,"
Nawaby says.
Getting that uniform structure is a process control issue. "We
know that with CO2 it works. There’s no doubt it does work,
but whether you’re going to get that ideal structure is going
to take the work…" Nawaby says.
Such work is important to Carlsson, who could potentially use
a polymer structure to repair knee tissue.
New knees
There are two possible ways to regenerate damaged knee cartilage.
The first is to put this cell-friendly foam scaffold into someone’s
body. If it were put into the knee, the movement of the joint going
back and forth would pump cells into the scaffold, Carlsson says.
The cells could then multiply and regenerate new tissue.
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Polymer scaffolds could help regenerate knee
cartilage that gets worn with age. |
Another option would be to multiply or expand the cells outside
the body. Cells would be extracted from the patient and placed in
a Petri dish. A cell biologist could get them to multiply. Once
a good number of healthy cells were grown they could be seeded into
the foam scaffold. This would become the implant that is surgically
placed in the knee, Carlsson says.
For these methods to work the foam scaffold has to be a perfect
fit. "…If you play the game correctly you can design
the size of the…holes for it so they’re big enough to
let the cells wander in, but not so big that they just come straight
back out again," Carlsson says.
A corn-based polymer called polylactic acid is being researched
to try to create a uniform scaffold. It’s a polymer that can
be designed to slowly biodegrade, Carlsson says.
"Biodegrade means it’s going to break down under the
actions of the enzymes in your body…at the position where
you implant it, so even though you’ve put cells in and it’s
foam to start with, the foam is going to progressively disappear,"
Carlsson says. "And you can design the system so it will disappear
at the same rate as the cells are generating their own matrix, their
own structure."
"Don’t rush out and say 'gee my knee is hurting I want
this fixed right now,'" Carlsson says. "We’re talking
future here."
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