Furdella, Kenneth
(2021)
Acute Preclinical Evaluation of Compliance-Matched and TGFβ2 Eluting Vascular Grafts.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
In the western world, coronary heart disease (CHD) from atherosclerosis kills over 365,000people annually and is the leading cause of death worldwide. Atherosclerosis can also act on the blood vessels in the arms or legs causing peripheral arterial disease(PAD), which affects over 6.5 million people over the age of 40. A standard intervention for CAD/PAD is a bypass surgery using a vascular graft. Commercially available synthetic grafts are a distant second option for CAD treatment due to their limited efficacy in smaller diameter vessels. Synthetic grafts or tissue engineered grafts (TEVG) often fail due to a compliance mismatch between the native vascular and the graft and an inability to remodel in vivo into a functional vessel. The ideal bypass graft for treatment of CAD/PAD would be an off-the-shelf graft that remains patent, compliance-matched, and remodels into a fully functional vessel. The goal of this dissertation is to use a rat interpositional aortic implantation model to evaluate the effect of compliance-matching on cellular infiltration in vivo, use transforming growth factor beta 2 (TGFβ2) to promote a desired in-vivo remodeling response, and develop a new method to evaluate graft drug delivery and degradation.
The compliance of the TEVGs was tuned to either match or be twice as stiff as rat aorta. These constructs were subsequently implanted into the abdominal aorta of Sprague Dawley rats and evaluated in-vivo using ultrasound and at a one-month explantation timepoint. The compliance-matched TEVGs remained compliant over the time course of the study and showed desired signs of remodeling with increased ratios of CD163/CD68 macrophages, increased smooth muscle cells, and increased collagen deposition when compared to the hypocompliant grafts (p<0.05). TGFβ2 was then added to the TEVG to evaluate cellular infilatration over an acute 5-day period. The low concentrations of TGFβ2 in the compliance-matched TEVG were found to increase SMC proliferation while the higher concentrations decreased the SMC population and promoted collagen deposition (p<0.05). The hypocompliant construct had no differences between all groups and concentrations. Finally, a new noninvasive method was developed to evaluate TEVG graft design, degradation, and drug delivery using photoacoustic imaging.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
3 September 2021 |
| Date Type: |
Publication |
| Defense Date: |
9 July 2021 |
| Approval Date: |
3 September 2021 |
| Submission Date: |
28 June 2021 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
98 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Tissue Engineered Vascular Grafts, Compliance, Transforming Growth Factor Beta 2, Photoacoustic Imaging |
| Date Deposited: |
03 Sep 2021 17:51 |
| Last Modified: |
03 Sep 2021 17:51 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/41366 |
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