Date of Award

January 2014

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Themis Kyriakides

Subject Area(s)

Biomedical engineering

Abstract

Electrospinning is a commonly proposed method for generating polymeric scaffolds for use in tissue and organ engineering. Using an electrospinning technique, we developed a small-diameter tissue engineered vascular graft (TEVG) composed of poly-ε-caprolactone-co-l-lactic acid (PCLA) for use in arterial circulation in the mouse. Characterization of grafts (n=6) revealed a lumen diameter of 526.4 ± 22.6µm, wall thickness of 234.8 ± 20.3µm, and fiber diameter of 882 ± 226nm. Based on our in vitro analysis showing loss of mechanical integrity by 12 weeks, we performed a pilot study to evaluate neovessel formation induced by the TEVG when implanted as an aortic interposition graft in immunodeficient mice over a 12-week period. Observations revealed excellent graft function, characterized by 100% patency, lack of stenosis or aneurysm, and excellent luminal matching with adjoining native vessel. Analysis of neovascular tissue development revealed an active and robust remodeling process characterized by an endothelial cell monolayer, transmural cellular infiltration, and extracellular matrix deposition. However, subsequent longer-term study revealed unanticipated catastrophic graft failure secondary to aneurysmal dilation and rupture at 14 weeks. These results provide insight into the shortcomings of electrospun scaffolds for arterial TEVG construction and highlight the importance of performing in vivo studies of sufficient duration to encompass the entire process of vascular neotissue formation and total scaffold degradation.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

Download

Share

COinS