From biomedical engineering and medical device development to genetic research
and biological process technology, IT researchers play a major role in the growing
field of biotechnology. Here is a look at 13 of the most innovative projects
underway.
For decades, scientists have aspired to create
effective biocompatible “replacement parts” for human
tissues damaged by injury and disease. Although many of these
new parts are fabricated from
inorganic substances, two University researchers have undertaken
the challenge of creating artificial coronary arteries from biological
material.
Daniel Mooradian, an assistant professor of biomedical
engineering, and Robert Tranquillo, an associate professor
of chemical engineering and materials science, began
developing the bioartificial artery as part of a collaborative
tissue engineering project in 1992.
The two researchers have been exploring ways to grow smooth muscle
cells that mimic both an artery's form and its internal structure
by using three-dimensional collagen matrices as a framework for
the cells.
A natural polymer-like collagen offers many advantages, explains
Tranquillo. Not only is collagen in ample supply, it also provides
an excellent natural substrate for cell growth that can be reabsorbed
into the body.
However, notes Mooradian, “When you build an artificial artery
on a biological base rather than a synthetic base, several things,
most notably mechanical strength, become an issue."
The team's early efforts, carried out by an undergraduate summer
fellow in Mooradian's laboratory, produced a cell-populated matrix
that maintained the shape of an artery but lacked the internal structure
and strength necessary to function.
"To be successful, we knew we would have to mimic the cellular
structure of an artery, not just its form,” says Mooradian.
That meant, among other things, increasing the artery's mechanical
strength and finding a way to grow its cells in a circular alignment.
"The biggest obstacle [to increasing mechanical strength]
is that collagen gels are so flimsy,” explains Timothy Girton,
a graduate student in Tranquillo's laboratory. However, advanced
techniques in materials science and engineering have provided important
insight into possible solutions.
Girton, Tranquillo, and Mooradian demonstrated that fabricating
the cells in a magnetic field and incubating them on a rigid cylindrical
rod greatly stiffens the resulting bioartificial artery. Moreover,
the magnetic field causes the collagen and cells to align around
the circumference as they do in a natural artery.
The researchers have issued several joint publications on the technique,
and a patent is pending.
"Magnetic field processing has the advantage of being a scale-independent
technique,” explains Tranquillo. “We can use it to create
arteries of any length, and the material aligns uniformly at all
points."
Having shown that magnetic fields can be used to engineer the artery's
microstructure, Tranquillo's team must now investigate how cyclical
stress affects its mechanical properties. Future experiments will
replace the rigid rod used during the incubation period with an
inflatable one that applies stress at the human pulse rate. This
is an area of great interest to Mooradian as well.
"The mechanical connections between cells and collagen are
reciprocal,” explains Mooradian. “Cells exert
a force on collagen, leading to compaction, remodeling,
and an increase in mechanical strength.” In turn,
the pulsing flow of blood deforms the collagen, exerting
pressure on the cells that changes their behavior.
"Our efforts have focused on understanding how this process
- 'mechanotransduction' - takes place at the molecular level,”
says Brenda Ogle, a graduate student in Mooradian's laboratory.
Ogle has identified specific proteins produced by vascular smooth
muscle cells that play a critical role in the cell-mediated strengthening
of the bioartificial artery.
"Our goal now is to manipulate those proteins - or the collagen
with which they interact - in order to control both structure and
function in the bioartificial artery,” adds Mooradian. This
approach is complementary to Tranquillo's, he says, and future collaborations
are likely.
Mooradian is currently organizing a symposium on tissue-engineered
blood vessels for the 1999 meeting of the Society of Biomaterials
in Providence, Rhode Island. “It's an opportunity to showcase
work being performed at the University of Minnesota and explore
how we can integrate our activities with [those of] experts from
around the world,” he says.
