Functional tissue engineering involves the study of the structure
and the function of living tissues, with the aim of recreating these
tissues in the laboratory. Such engineered tissues could then be
used to replace damaged body parts, or to study complex biological
problems in a controlled environment. The field is highly multidisciplinary,
drawing on expertise in the areas of biology, physiology, computational
modeling, transport phenomena, mechanics, and many others.
A key issue in functional tissue engineering is the ability to
control cell function in three-dimensional engineered tissues. This
is a requirement in order to promote appropriate tissue development
in vitro, as well as to ensure physiological tissue function in
vivo. A variety of strategies have been developed to achieve these
ends, including the application of biochemical and mechanical stimulation,
as well as the use of genetic modification to control cell function.
Current research in our laboratory focuses on the use of extracellular
environments to control cell function and the development of engineered
tissues. In particular, we are interested in naturally-derived hydrogels
for use as scaffolds in tissue engineering, and their effects on
cell phenotype and function. One focus of this work is to create
better matrices for vascular tissue engineering applications, and
to study vascular biology. Knowledge of how engineered extracellular
environments can affect cell function can also be extended to the
field of biotechnology, for example in the optimization of protein
production in mammalian cell bioreactors. Each of these areas is
discussed briefly below.
Naturally derived polymers such as agarose, alginate, collagen
and fibrin have been used widely in tissue engineering applications.
However, a more complete understanding of the structure of these
different matrices, how they interact with cells and how they affect
cell function would be of great benefit to a variety of fields.
Thorough characterization of the properties of these different matrices
includes chemical characterization, structural analysis, mass transfer
evaluation as well as testing of mechanical properties. The primary
goal of this research is to understand how each of these properties
affects tissue-specific cell functions, and how matrix properties
can then be tailored to direct these functions.
Diseases of the heart and blood vessels are among the most costly
health problems in modern society, and there is an urgent need for
both an improved understanding of the disease process as well as
improved treatments for affected patients. We are developing an
engineered blood vessel composed of isolated vascular smooth muscle
cells embedded in a matrix of collagen and fibrin. A key issue is
the change in cell function that is observed when smooth muscle
cells are removed from their native environment. Our research aims
to understand this change, and to define extracellular environments
that can prevent or reverse this shift. This work is also relevant
to understanding the mechanisms of certain vascular diseases, such
as atherosclerosis and hypertension, in which phenotype shifts are
implicated. In addition, we are interested in improving the mechanical
properties of the engineered construct in order to allow its use
as a vascular replacement.
Mammalian cell bioreactor cultures have the potential to produce
fully functional complex proteins that bacterial or insect cells
are unable to produce. We are studying how mammalian cell function
can be better controlled in bioreactor systems, in order to maximize
the efficiency of therapeutic protein production. Live mammalian
cells are embedded in beads formed from a variety of hydrogel matrices,
and the effect of the matrix on cell function is assessed. Use of
more physiologically appropriate extracellular matrices in a spherical
geometry may enhance cell function while improving mass transfer
characteristics. Potential applications of this technology are to
enhance transfection of target cells by non-viral vectors, or to
grow and maintain stem cells in bioreactor systems, since the properties
of the matrix could be tailored to promote cell proliferation or
desired differentiated functions.
