Johns
Hopkins tissue engineers have used tiny, artificial fiber scaffolds
thousands of times smaller than a human hair to help coax stem cells
into developing into cartilage, the shock-absorbing lining of elbows and
knees that often wears thin from injury or age.
Reporting online June 4 in the Proceedings of the National Academy of Sciences,
investigators say they have produced an important component of
cartilage in both laboratory and animal models. While the findings are
still years away from use in people, the researchers say the results
hold promise for devising new techniques to help the millions who endure
joint pain.
“Joint
pain affects the quality of life of millions of people. Rather than
just patching the problem with short-term fixes, like surgical
procedures such as microfracture, we’re building a temporary template
that mimics the cartilage cell’s natural environment, and taking
advantage of nature’s signals to biologically repair cartilage damage,”
says Jennifer Elisseeff, Ph.D., Jules Stein Professor of Ophthalmology
and director of the Translational Tissue Engineering Center at the Johns
Hopkins University School of Medicine.
Unlike
skin, cartilage can’t repair itself when damaged. For the last decade,
Elisseeff’s team has been trying to better understand the development
and growth of cartilage cells called chondrocytes, while also trying to
build scaffolding that mimics the cartilage cell environment and
generates new cartilage tissue. This environment is a three-dimensional
mix of protein fibers and gel that provides support to connective tissue
throughout the body, as well as physical and biological cues for cells
to grow and differentiate.
In
the laboratory, the researchers created a nanofiber-based network using
a process called electrospinning, which entails shooting a polymer
stream onto a charged platform, and added chondroitin sulfate—a
compound commonly found in many joint supplements—to serve as a
growth trigger. After characterizing the fibers, they made a number of
different scaffolds from either spun polymer or spun polymer plus
chondroitin. They then used goat bone marrow-derived stem cells (a
widely used model) and seeded them in various scaffolds to see how stem
cells responded to the material.
Elisseeff
and her team watched the cells grow and found that compared to cells
growing without scaffold, these cells developed into more voluminous,
cartilage-like tissue.
“The
nanofibers provided a platform where a larger volume of tissue could be
produced,” says Elisseeff, adding that three-dimensional nanofiber
scaffolds were more useful than the more common nanofiber sheets for
studying cartilage defects in humans.
The
investigators then tested their system in an animal model. They
implanted the nanofiber scaffolds into damaged cartilage in the knees of
rats, and compared the results to damaged cartilage in knees left
alone.
They
found that the use of the nanofiber scaffolds improved tissue
development and repair as measured by the production of collagen, a
component of cartilage. The nanofiber scaffolds resulted in greater
production of a more durable type of collagen, which is usually lacking
in surgically repaired cartilage tissue. In rats, for example, they
found that the limbs with damaged cartilage treated with nanofiber
scaffolds generated a higher percentage of the more durable collagen
(type 2) than those damaged areas that were left untreated.
“Whereas
scaffolds are generally pretty good at regenerating cartilage protein
components in cartilage repair, there is often a lot of scar
tissue-related type 1 collagen produced, which isn’t as strong,” says
Elisseeff. “We found that our system generated more type 2 collagen,
which ensures that cartilage lasts longer.”
“Creating
a nanofiber network that enables us to more equally distribute cells
and more closely mirror the actual cartilage extracellular environment
are important advances in our work and in the field. These results are
very promising,” she says.
Other
authors included Jeannine M. Coburn, Matthew Gibson, Sean Monagle and
Zachary Patterson, all from The Johns Hopkins University.
The
research was supported by grants R01 EB05517, F31 AG033999 and F30
AG034807 from the National Institutes of Health.
