Multifunctional Silk Nerve Guides for Axon Outgrowth.
nerve regeneration is a critical issue as 2.8% of trauma patients present with this type
of injury, estimating a total of 200,000 nerve repair procedures yearly in the United
States. While the peripheral nervous system exhibits slow regeneration, at a rate of 0.5
mm - 9 mm/day following trauma, this regenerative ability is only possible under certain
conditions. Clinical ... read morerepairs have changed slightly in the last 30 years and standard
methods of treatment include suturing damaged nerve ends, allografting, and
autografting, with the autograft the gold standard of these approaches. Unfortunately,
the use of autografts requires a second surgery and there is a shortage of nerves
available for grafting. Allografts are a second option however allografts have lower
success rates and are accompanied by the need of immunosuppressant drugs. Recently there
has been a focus on developing nerve guides as an "off the shelf" approach. Although
some natural and synthetic guidance channels have been approved by the FDA, these nerve
guides are unfunctionalized and repair only short gaps, less than 3 cm in length. The
goal of this project was to identify strategies for functionalizing peripheral nerve
conduits for the outgrowth of neuron axons in vitro. To accomplish this, two strategies
(bioelectrical and biophysical) were indentified for increasing axon outgrowth and
promoting axon guidance. Bioelectrical strategies exploited electrical stimulation for
increasing neurite outgrowth. Biophysical strategies tested a range of surface
topographies for axon guidance. Novel methods were developed for integrating electrical
and biophysical strategies into silk films in 2D. Finally, a functionalized nerve
conduit system was developed that integrated all strategies for the purpose of
attaching, elongating, and guiding nervous tissue in vitro. Future directions of this
work include silk conduit translation into a rat sciatic nerve model in vivo for the
purpose of repairing long (> 3 cm) peripheral nerve
Thesis (Ph.D.)--Tufts University, 2012.
Submitted to the Dept. of Biomedical Engineering.
Advisor: David Kaplan.
Committee: Mark Cronin-Golomb, Michael Levin, and Kacey Marra.
Keyword: Biomedical engineering.read less