Tamimi, Ehab A
(2018)
Towards a compliance-matched biopolymer tissue engineered vascular graft.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Cardiovascular disease (CVD) continues to be the largest cause of death in the United States with the highest percentage of CVD-related deaths attributed to coronary artery disease (CAD). Coronary artery bypass grafts (CABG) used to treat CAD often fail due to compliance mismatch, which can lead to anastomotic intimal hyperplasia and thrombosis. While autologous grafts (i.e. saphenous vein) are considered the golden standard for CABG, they have been shown to have lower patency in smaller diameter vessels (<2 mm) and commonly fail due to poor graft quality, graft unavailability, and graft compliance mismatch with the native vessel. Tissue engineered vascular grafts (TEVGs) offer an alternative for CABG that be designed to be biocompatible, non-thrombogenic, compliance-matched, and produced with good durability and deliverability. Currently, small-diameter synthetic TEVGs have shown poor patency rates due to acute thrombogenicity, anastomotic intimal hyperplasia and compliance mismatch to native tissue. One strategy for improving TEVGs is the inclusion of elastic and compliant biological polymers native to the body. TEVGs fabricated from natural biopolymers may have the potential to be more biocompatible and biodegradable. Additionally, natural biopolymers are generally hydrophilic and may provide better physiological support for cell attachment by providing specific integrin interaction sites, which could enhance cell adhesion and proliferation.
Small-diameter acellular electrospun gelatin/fibrinogen cylindrical TEVGs were fabricated and mechanically characterized. Gelatin/fibrinogen constructs crosslinked with glutaraldehyde were found to compliance match porcine left anterior descending coronary artery. The results of this study demonstrate the feasibility of meeting mechanical specifications expected of native arteries by tuning compliance through manipulation of crosslinking time. I have also developed an experimental/computational approach to fabricate an acellular biomimetic hybrid tissue engineered vascular graft composed of alternating layers of electrospun porcine gelatin/polycaprolactone (PCL) and human tropoelastin/PCL blends with the goal of compliance-matching to rat abdominal aorta, while maintaining specific geometrical constraints. All constructs were mechanically characterized and modeled using a modified Fung-type strain energy equation. I have shown that we can tune the mechanical properties of our hybrid synthetic/protein grafts by varying the ratio of protein to synthetic polymer. Fabricated layered optimized grafts were successfully compliance matched and geometry matching to rat abdominal aorta.
Finally, this dissertation also discusses the results of an ocular biomechanics study where the biomechanical properties of the posterior sclera were determined as a function of racioethnicity. This was done to explain the disparity in glaucoma between racioethnic groups (African descent, European descent and Hispanic ethnicity). The mechanical theory of glaucoma rests on the assumption that mechanical damage forces acting on the optic nerve cause a loss of retinal ganglion cell function. Sequential digital image correlation was used to recreate the scleral geometry and determine surface deformations as a function of intraocular pressure. Statistical analysis revealed differences between the three racioethnic group in tensile and compressive principal strains. This may provide a unique opportunity for the development of novel diagnosis and treatment opportunities.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
17 September 2018 |
| Defense Date: |
29 August 2018 |
| Approval Date: |
24 January 2019 |
| Submission Date: |
19 September 2018 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Number of Pages: |
169 |
| 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: |
vascular, graft, compliance, tissue, engineering, biomechanics |
| Date Deposited: |
24 Jan 2019 14:33 |
| Last Modified: |
19 Jul 2024 19:17 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/35327 |
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