Silk Implants for Localized Small Molecule Drug Delivery to Treat Traumatic Brain Injury.
brain injury (TBI) is the leading cause of death and disability worldwide. Resulting
from blunt or penetrating forces to the head, TBI can affect any population of
individuals. Following primary injury, or the initial mechanical insult, brain tissue
undergoes secondary injury, notably necroptosis, or controlled tissue death.
Administration of necroptosis inhibitors and ... read moreother small molecules to alter the
signaling cascade of tissue death has the potential to minimize the harmful short-term
and long-term effects of secondary injury. Unfortunately, pharmaceuticals designed to
target the brain have one major obstacle that medications to other sites of the body do
not encounter - the blood barrier (BBB), a highly selective semi-permeable endothelial
cell capillary network that protects the brain from toxic substances. The few drugs that
successfully cross the BBB are only able to do so after reaching high systemic
concentrations, adversely affecting the rest of the body. Invasive approaches by means
of drug-eluting biodegradable polymer implants show greater potential for localized
delivery. Among the most successful natural polymers is silk fibroin which boasts
several qualities such as biocompatibility, biodegradability, and extraordinary
tunability of chemical and mechanical properties, making it a very useful biomaterial
for controlled local release of drugs to the brain for the treatment of TBI. In this
research, two silk-based implants, thin silk films and silk-HRP hydrogels, were tested
for their ability to consistently deliver small molecules to the brain and subsequently
prevent cell and tissue death following a controlled cortical impact mouse
Thesis (M.S.)--Tufts University, 2015.
Submitted to the Dept. of Biomedical Engineering.
Advisor: David Kaplan.
Committee: Qiaobing Xu, Barry Trimmer, and Michael Whalen.
Keyword: Biomedical engineering.read less