Functionalization and characterization of silk based gel-spun vascular grafts.
Vascular grafts made from synthetic materials such as ePTFE (Teflon) and PET (Darcon)
demonstrate low rates of patency in the small (1-6mm) inner diameter (ID) regime, which
is attributed to thrombosis and anastamotic intimal hyperplasia. Here we propose the
utilization of a functionalized acellular and absorbable gel-spun silk vascular graft as
an alternative material to ... read moresynthetic grafting in patients with severe Peripheral
Arterial Disease (PAD). The silk tubes luminal smoothness, porosity and degradation
profiles were first optimized in vitro to promote cellular infiltration and
revascularization. The scaffolds luminal walls were then modified with
chemically-conjugated heparin and assessed in vitro for platelet adhesion and
activation. The molecular weight of the silk solution was used in conjunction with
optimized gel spinning conditions in order to generate silk tubes of varying porosity,
which were then implanted into the infarenal abdominal aortas of Sprague-Dawley rats. At
time points 1-month, 3-month, and 6-month post-implantation, grafts were retrieved and
histologically assessed via basic stains and immunohistochemistry for vascular-specific
markers. Patency was maintained independent of tube porosity and we observed minimal
neointimal hyperplasia, as grafts were continuously lined with trans-anastomotic
endothelial cells. High levels of cellular infiltration and deposition of extracellular
matrix in the high-porosity formulations could also be observed. These behaviors of
long-term in vivo results shed light into the advantages of utilizing silk fibroin for
microvascular scaffolding and subsequent larger animal model
Thesis (M.S.)--Tufts University, 2015.
Submitted to the Dept. of Biomedical Engineering.
Advisor: David Kaplan.
Committee: Peter Kim, and Fiorenzo Omenetto.
Keyword: Biomedical engineering.read less