Chris Madl |
|
email: cmadl AT
stanford DOT edu
Dept: Bioengineering
S.M.
Engineering Sciences (Bioengineering),
Harvard University
A.B. Engineering Sciences (Biomedical Engineering) and Chemistry,
Harvard University
|
|
Nervous
system
trauma, including spinal cord injury and peripheral nerve damage, often
results
in severely debilitating conditions for patients, with limited
clinically available
treatment options. There has been much
interest in developing regenerative therapies for such injuries,
however,
several challenges remain to their implementation.
Within the central nervous system, nerve
regeneration is limited by the body’s natural inflammatory
response that
rapidly replaces injured spinal cord tissue with scar tissue. Furthermore, this inflammatory process
results in significant oxidative damage to the surviving neurons, which
further
hampers regeneration. One strategy to
remediate
the damage caused by this inflammatory response is to implant a
material at the
injury site that is conducive to the growth of neurons and protects
them from
further damage, while limiting the formation of scar tissue. Recent work with engineered elastin-like
proteins (ELPs) has shown that the extent of neurite growth through the
material can be modulated by controlling the elastic modulus of, and
cell
adhesion ligand density within, the material.
Such “cell-instructive” materials can be made
“cell-responsive” by
incorporating functionalities that react based on the presence of
certain
cellular products. For instance, it has
been reported that the serine protease, urokinase plasminogen activator
(uPA),
is secreted from axonal growth cones. My
project investigates the incorporation of uPA-cleavable sequences into
ELP
hydrogels to either modulate the degradation of the material itself or
to
selectively release compounds to aid in cell survival.
uPA degradable ELP may allow for localized
degradation of the hydrogel matrix at the tips of growing neurites, and
patterning of this selectively degradable ELP would allow for spatial
control
over neurite growth. Certain small peptides have been reported to
protect
neurons against oxidative damage, such as that which occurs following a
spinal
cord injury. Conjugating these
neuroprotective peptides to ELP via a uPA cleavable linker may allow
for
triggered release of these compounds due to neuronal growth, protecting
the
neurons within the material from further damage while aiding in
regeneration.
|