Luketich, Samuel K.
(2018)
Degradation of engineered polyurethane heart valves in a mechanically demanding environment with variable mixing of polyester and polycarbonate soft segments.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Valvular heart disease (VHD) is a major source of morbidity and mortality leading to approximately 290,000 valve replacement surgeries worldwide each year. Current replacement prosthetics include mechanical and bioprosthetic heart valves, which are burdened by chronic anticoagulation therapy and tissue degeneration, respectively, as well as an inability to grow and remodel. Tissue engineered heart valves (TEHVs) have been proposed to overcome these limitations by providing a scaffold that is designed to be gradually replaced by autologous functional tissue. As such, TEHVs should degrade at a rate matching new tissue formation to achieve proper function and avoid structural failure.
Biodegradable polyurethane elastomers are suitable candidates for TEHVs and offer tunable degradability based on soft segment chemistry. Polyester soft segments in poly(ester urethane)urea (PEUU) generate faster degradation than polycarbonate soft segments in poly(carbonate urethane)urea (PCUU). These biodegradable polyurethanes can be electrospun into fully assembled, fibrous TEHVs. The objectives of this study were to evaluate the in vitro degradation profile of three polyurethane soft segment mixing strategies and the effects of a mechanically demanding environment on the degradation rate. Equal ratios of faster-degrading polyester and slower-degrading polycarbonate segments were mixed into polyurethanes using three strategies: 1) soft segment mixing during synthesis to form poly(ester carbonate urethane)urea, 2) physical blending of PEUU and PCUU polymers during solvation to form a single solution, and 3) electrospinning from two independent streams of PEUU and PCUU solutions. These mixing strategies varied the chemical composition of the polymer chains and electrospun fibers between groups.
Electrospun TEHVs from each mixing strategy were subjected to accelerated degradation in a pulse duplicator with enzymatic solution for two weeks. Relative degradation rates were quantified based on scaffold mass and thickness loss, macro- and microscopic structural changes, and viscosity reduction. Additionally, biaxial mechanical compliance was monitored throughout degradation and initial scaffold blood compatibility was assessed. Soft segment mixed TEHVs had the most degradation while co-spun TEHVs degraded very little. Additionally, mechanical strength was maintained for each mixing strategy throughout degradation. Findings of this study are instrumental in efficiently designing TEHVs where tunable degradation is critical to match the in vivo tissue formation rate.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Luketich, Samuel K. | skl13@pitt.edu | skl13 | |
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| ETD Committee: |
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| Date: |
11 June 2018 |
| Date Type: |
Publication |
| Defense Date: |
27 March 2018 |
| Approval Date: |
11 June 2018 |
| Submission Date: |
9 April 2018 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
123 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Chemical Engineering |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Tissue engineered heart valve, polyurethane, degradation, polyurethane soft segment mixing |
| Date Deposited: |
11 Jun 2018 17:21 |
| Last Modified: |
11 Jun 2019 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/34188 |
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