Date of Award

January 2014

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Jay D. Humphrey

Second Advisor

Christopher K. Breuer

Subject Area(s)

Biomedical engineering, Biomechanics, Surgery

Abstract

We used a murine model to assess the in vivo evolving biomechanical properties of tissue engineered vascular grafts (TEVGs) implanted in the arterial circulation. The initial polymeric tubular scaffold was fabricated from (poly)lactic acid (PLA) and coated with a 50:50 copolymer of (poly)caprolactone and (poly)lactic acid (P[PC/LA]). Following seeding with syngeneic bone marrow derived mononuclear cells, the TEVGs (n=50) were implanted as aortic interposition grafts in wild-type mice and monitored serially using ultrasound. A custom biaxial mechanical testing device was used to quantify in vitro the circumferential and axial mechanical properties of grafts explanted at 3 or 7 months. At both times, the TEVGs were stiffer than native tissue in both directions. We treated the TEVGs with either elastase or collagenase to delineate individual contributions of these structural proteins. Elastin conferred an insignificant contribution whereas collagen contributed significantly to TEVG stiffness. The mechanical properties were compared with the underlying microstructure, which was inferred from traditional histology and immunohistochemistry. Analysis revealed smooth muscle cell layers, appropriate collagen deposition, and increasing elastin production. In addition, significant amounts of residual scaffold were present at both 3 and 7 months, which likely contributed to the high stiffness seen in mechanical testing. These results suggest that PLA may have inadequate in vivo degradation, which impairs cell-mediated development of vascular neotissue having properties closer to native arteries. Assessing contributions of individual components, such as elastin and collagen, to the developing neovessel promises to guide computational modeling that may help to optimize the design of the TEVG.

Comments

This is an Open Access Thesis.

Share

COinS