Defense Date

2011

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

First Advisor

Gary Bowlin

Abstract

Tissue engineering is an interdisciplinary field that aims to restore, maintain, or improve diseased or damaged tissues. Electrospinning has become one of the most popular means to fabricate a scaffold for various tissue engineering applications as the process is extremely versatile and inexpensive. The ability for electrospinning to consistently create nanofibrous structures capable of mimicking the native extracellular matrix (ECM) is the basis behind why this technique is so successful in tissue engineering. Cardiovascular disease has been the leading cause of death in the United States for over 100 years, and because of this, the need for coronary artery replacements is in serious demand. More specifically, small diameter vessels (<6 mm I.D.) are most needed, due to the fact that they are most often affected and the current clinical replacements provide less than optimal long-term patency and regenerative ability. Tissue engineering of vascular grafts has been investigated for over 50 years, however, synthetic replacements made of Dacron® and expanded-poly(tetrafluoroethylene) (e-PTFE) still remain the clinical standard. This study examines a variety of different ways to alter different characteristics of electrospun constructs, to create scaffolds that would be favorable for use as a blood vessel replacement; the end goal being the creation of an acellular bioresorbable vascular graft that would provide sufficient mechanical support to withstand physiological forces, as well as ample biocompatibility to allow host cells to infiltrate and regenerate the graft as the structure degrades. As a way of tailoring the mechanical and thermal properties of a scaffold to be more conducive to that of a native artery, a novel co-polymer was created from the random copolymerization of two monomers; 1,4-Dioxan-2-one (DX) and DL-3-methyl-1,4-dioxan-2-one (DL-3-MeDX) were mixed at different ratios and electrospun, forming nanofibrous scaffolds that exhibited different mechanical and thermal properties. Next, scaffolds were electrospun from natural and synthetic polymers, and the potential for these materials to elicit the formation of an acute thrombotic occlusion was investigated by quantifying tissue factor expression from monocytes using a novel technique. Tissue factor expression by monocytes on the electrospun natural and synthetic polymer scaffolds was compared to that of e-PTFE to determine their potential for use as vascular graft materials. Platelet-rich plasma (PRP), a naturally occurring blood component which is comprised of supraphysiologic concentrations of autologous growth factors, was activated and lyophilized to form a preparation rich in growth factors (PRGF). PRGF was electrospun for the first time, to create a scaffold that would mimic the role of the native ECM in the wound healing cascade. Characterization of these scaffolds proved their bioactivity was enhanced, with cell infiltration occurring throughout the structures in as little as 3 days. Lastly, PRP/PRGF and/or heparin were incorporated into electrospun PCL scaffolds as a means of enhancing the regenerative potential and reducing the thrombogenic potential of the scaffolds, while supplying the constructs with mechanical stability. The release of several pro-regenerative growth factors and chemokines from the PRP incorporated scaffolds was analyzed and the effect of PRP and heparin on scaffold degradation characteristics was determined. Additionally, cell proliferation, migration, sprout formation, and chemokine release were evaluated, and results from these experiments proved the addition of PRP could enhance the regenerative potential of the electrospun scaffolds. The results from this study reveal the variety of ways in which a number of characteristics of an electrospun scaffold can be altered to create a more ideal bioresorbable vascular graft that has the potential to be regenerated within the body, while providing enough mechanical support for this to occur over time.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

December 2011

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