Over 100,000 peripheral nerve injuries (PNI) including motor vehicle and combat
accidents occur annually in the U.S. and Europe. In addition, PNI accounts for nearly one-
fourth of the pediatric nerve damage. Common causes in children include direct trauma
related to birth (e.g. brachial plexus), motor vehicle accidents, as well as tumor, vascular,
and compression injuries. In the U.S., approximately $150 billion is spent each year as a
result of nerve injury, with 87% of these costs due to lost production outside of healthcare
system. The majority of patients are left with lifelong disability and functional deficits,
creating a major personal and societal burden. The current gold standard is to use a
patient's own nerves harvested from one location to treat nerve defects (>10 mm) at injury
site. However, the drawbacks are significant including the limited availability of the donor
nerve, size of donor nerve, and scarring and complications occurring at the surgical sites.
More recently, human neural stem cells (hNSCs) have emerged as a potential treatment
for neural recovery. However, there is limited graft survival (5-20%) immediately
following transplantation due to acute inflammatory/immune response, neurotrophic
factor withdrawal, and oxidative stresses in the complex microenvironment. This
subsequently diminishes the therapeutic effectiveness of hNSC therapy. It is crucial to
understand how transplanted hNSCs are influenced by their microenvironmental cues to
sustain their viability and elicit the desired cellular behaviors to enhance nerve repair.
Stem cells interact with their microenvironment through biochemical factors,
matrix proteins, and cell-cell interactions. My research focuses on using regenerative
strategies to biophysical, biochemical, and bioelectrical microenvironment to further
enhance the therapeutic potential and sustain the survival of transplanted hNSCs to
repair nerve defects. Specifically, hNSCs will be electrically stimulated and encapsulated
in silicon nanopore membrane (SNM) for enhanced therapeutic effectiveness and survival.
In addition, physical rehabilitation will be implemented to promote nerve recovery. The
goal of this research is to understand biological pathways related to peripheral nerve
repair through biochemical modulation, and electrical and physical rehabilitation to
enhance the therapeutic potential of hNSCs. By understanding the interplay between
stem cells and various forms of rehabilitation strategies (e.g. electrical stimulation,
physical exercise), we can investigate new device approaches and identify essential
pathways that can translate into better neural recovery and nerve regeneration strategies
for PNI in humans.