engineering

::: Visionary :::

technology

Engineering
::: Designing an Artificial Cornea
Using Polymer Networks :::
by Andy Dow
Photo Credit: National Eye Institute, National Institutes of Health

W
hile medicine currently lacks a synthetic implanting the artificial cornea.
substitute for a fully functional human eye, To achieve this strength and high swellability, Frank’s
scientists at Stanford are making significant research group used an interpenetrating polymer network.
progress in engineering some of the eye’s most critical Network formation begins with what Frank describes as a
parts. Dr. Curtis Frank, Professor of Chemical Engineering,
in collaboration with Dr. Christopher Ta, Professor of
Ophthalmology at the School of Medicine, and a number A synthetic material
of other researchers have developed a new hydrogel with
biomimetic properties—those that mimic a biological that not only emulates,
substance—that is a prime candidate for use as an artificial
cornea. Their research holds exciting promise for the
millions of people worldwide affected by corneal disease
but also successfully
who may lack access to transplant tissue.
integrates with biological
Molecular Mechanics of Strength and Elasticity
One of the most important properties of the hydrogel, as tissue could affect
its name implies, is its ability to swell in water. High water
content facilitates the diffusion of glucose, an important corrective ophthalmology
::: worldwide. :::
molecule that aids in the growth of a healthy layer of cells
over the cornea. The material’s ability to swell in water is
related to its tensile strength—essentially a measure of
the force required to pull the material apart. The optimal
material would be stretchy, yet difficult to fracture. As an “3-D fishnet” of one material—in this case, poly(ethylene
added benefit, the combination of elasticity and durability glycol). When placed in water, this polymer (consisting of
increases the ease of suturing in a surgical procedure for repeating ethylene glycol monomers) remains covalently

The hydrogel consists of

two entangled polymer
networks. In aqueous
solution, these polymers
hydrogen bond with
water and with one
another to form a strong,
optically clear material.

Photo Credit: David Myung

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engineering
+
technology

The cornea is a clear dome-

shaped surface that forms
the eye’s outermost layer. It
serves as a focusing lens and
a filter that shields the rest of
the eye from harmful matter,
e.g. bacteria, dust or ultraviolet
radiation. Artificial cornea
replacements will hopefully
supplement low donor tissue
availability in many countries
around the world.
Photo Credit: ©sxc.hu/Stacey Thompson

This successful and controllable epithelial adhesion is

one of a number of factors that set this material apart
from previously designed commercial devices, none
::: of which support such epithelial growth. :::
connected and swells. To create the interpenetrating network,
they imbibe the first network with a mixture of acrylic acid
monomers and water. At this point, the water serves as
a sort of Trojan horse for carrying the nascent polymer
inside the poly(ethylene glycol). These poly(acrylic acid)
chains weave in and out of the swollen poly(ethylene glycol)
network so that the two networks interlock. Even though
the two polymers do not covalently bond to one another,
their complex entanglement gives the material considerable
strength. “They are co-continuous,” Frank remarks. “You
Interdisciplinary Success
Creating an artificial cornea involves many different engineering
considerations, and its design therefore requires expertise in many
areas. It should come as no surprise that the scientists tackled a
project with biological, clinical and materials science dimensions
through an interdisciplinary approach, pooling some of Stanford’s
best resources of knowledge. Development of the hydrogels was a
collaborative effort between the Chemical Engineering Department
and the School of Medicine. Professor Curtis Frank and other chemical
engineers, including MD/PhD student David Myung, worked closely
with Professor Christopher Ta of Ophthalmology, another principal
investigator for the project. Ta clarified the clinical needs that the
chemical engineers must meet in their design considerations,
such as optical clarity and an epithelial cell layer to defend against
infection. Jennifer Cochran, Assistant Professor in Bioengineering,
also contributed to the research effort through her expertise in cell
biology. “The materials science needs to be developed in the context
of what the interfacial and cell biology needs are, as well as what the
clinical needs are,” comments Frank. “One component alone couldn’t
solve the problem.”
couldn’t pull them apart.”
Thermodynamic Considerations
While the mechanical properties of the material contribute
to its strength, Frank points out that thermodynamic factors
play a role as well. Part of the tensile strength comes from
favorable hydrogen bonding between the two polymers
that render the hydrogel energetically stable. Hydrogen
bonds are a type of strong intermolecular force between
partially positive hydrogen atoms on one molecule and an
electronegative atom on another. Although Frank initially
worried that hydrogen bonding with water might overwhelm
those between polymers, he believes that the strong
intermolecular forces between the polymer networks do in
fact lend extensive strength to the material.
In addition to strength, these hydrogen bonds play a
significant role in another important engineering parameter
for a cornea: transparency. Because the polymers undergo
hydrogen bonding with both water and each other, they
are soluble in water and miscible with one another. The
thermodynamically favorable interactions among molecules
of water and the two polymers lead to a well-integrated
material with all three components in a single phase. This
uniformity creates optical clarity.
Bio-Integration
To ensure that the hydrogel would provide a clear window
for sight once implanted in an eye, the researchers had to
prevent unwanted protein deposits from building up a
clouding layer of cell debris on the surface. The team knew
from empirical observations that both poly(ethylene glycol)
and poly(acrylic acid) are resistant to non-specific protein

40 stanford scientific
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adsorption. However, the full situation is

more complicated. Some cellular growth
on the hydrogels is necessary for healthy
biological acceptance of the new material,
and a layer of epithelial cells on the surface
of the cornea provides an important natural
barrier to bacterial infection.
After demonstrating that cells would
not grow on the engineered material
without surface modification, Frank’s team
developed a surface coupling technique to
make the hydrogel controllably attractive
to cells. While avoiding unwanted protein
adsorption, they can pattern the material’s

Photo Credit: David Myung

surface with bifunctional chemical linkers
that bind to proteins at specific regions
and promote epithelial cell growth at those
areas. “You start with a system that you
want to remain relatively uncontaminated,
and then you can control cell growth by
virtue of the surface pattern,” Frank explains.
Seeing Ahead
This successful and controllable epithelial adhesion is
one of a number of factors that set this material apart from
previously designed commercial devices, none of which
support such epithelial growth. “This material is new for any
kind of ocular application,” notes Frank. It appears to be
heads above others in performance thanks to its mechanical,
thermodynamic and biocompatible properties. “We have
a material right now that is very good,” he says, “and we
want to understand why it’s good so that we can potentially
make it better.” Frank acknowledges that the next steps
in this research toward achieving applicability will be to
develop what is now a highly qualitative knowledge of these
properties into a quantitative understanding.
A synthetic material that not only emulates, but also
successfully integrates with biological tissue could affect
corrective ophthalmology worldwide. In fact, Ta notes that
it would greatly impact countries outside the U.S., where
The hydrogels synthesized at Stanford have a clear center and a peripheral
surface patterned to foster selective growth of natural cells. These strong
polymer materials hold up to 85 percent of their weight in water.
smaller donor pools and large infrastructure costs for
harvesting and transporting corneas create a shortage of
tissue for traditional transplant surgery. Even in the U.S., an
appropriately designed material might surpass donor tissue
in visual recovery periods and biological acceptance after
surgery. Some might caution that until full application of
the material is realized, seeing is believing. For many future
beneficiaries, seeing will be all the belief they need. S
ANDY DOW is a sophomore planning to major in Chemical
Engineering. His goal is to develop alternative energy technologies.
In addition to writing, he enjoys music, good literature and spending
time at the beach.
To Learn More
Visit the National Eye Institute website:
http://www.nei.nih.gov/health/cornealdisease/

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