Date of Award

2011

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Christopher K. Breuer

Subject Area(s)

Biomedical engineering

Abstract

Cardiovascular disease is the leading cause of death in the world. In the United States alone, the American Heart Association estimates the cost of treating CVD in 2009 to be $475.3 billion. Suitable autologous blood vessels are often scarce, especially for patients who require multiple procedures. There is a global demand for improved, biocompatible vascular conduits to address these shortcomings. Biodegradable tubular scaffolds are currently being evaluated as vascular grafts in the surgical treatment of cardiovascular disease. Seeding scaffolds with bone marrow-derived mononuclear cells (BMCs) prior to implantation has been shown to significantly improve outcomes. However, the role these cells play is poorly understood.

Various inferior vena cava (IVC) interposition models in recipient mouse models were used to evaluate the developmental remodeling process of engineered blood vessels. Detailed analysis of vascular graft morphology and CT imaging provide standardization of graft analysis for various TEVG models. Seeding scaffolds with BMCs significantly improved patency rates and graft development. However, seeded BMCs did not directly contribute to the cellularity of the developing vessel, and were not detectable by three weeks. Rather, BMCs were found to produce significant amounts of various cytokines in response to the scaffold biomaterials, resulting in early recruitment of recipient mouse monocytes to the scaffold and subsequent improvement in vascular neotissue formation. A series of cell-tracking experiments demonstrate vascular cell in-growth from adjacent vascular tissue. These results indicate that engineered blood vessels mature through an early cytokine induced inflammatory response that induces native tissue regeneration.

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