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Degradation of engineered polyurethane heart valves in a mechanically demanding environment with variable mixing of polyester and polycarbonate soft segments

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 (Unpublished)

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[img] Video (QuickTime) (Video 1: Representative video showing the electrospinning process to fabricate fully assembled, trileaflet, biodegradable heart valves using the heart valve-shaped mandrel.)
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[img] Video (AVI) (Video 2: Representative video of an electrospun TEHV in the pulse duplicator; front view showing the leaflet coaptation at the free edge during pulsatile flow.)
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[img] Video (AVI) (Video 3: Representative video of an electrospun TEHV in the pulse duplicator; side view showing the sutures from the commissures to the posts to simulate chordae tendineae.)
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[img] Video (AVI) (Video 4: Soft segment mixed electrospun TEHV at 0 days of degradation.)
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[img] Video (AVI) (Video 5: Soft segment mixed electrospun TEHV at 3 days of degradation.)
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[img] Video (AVI) (Video 6: Soft segment mixed electrospun TEHV at 7 days of degradation.)
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[img] Video (AVI) (Video 7: Soft segment mixed electrospun TEHV at 14 days of degradation.)
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[img] Video (AVI) (Video 8: Physically blended electrospun TEHV at 0 days of degradation.)
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[img] Video (AVI) (Video 9: Physically blended electrospun TEHV at 3 days of degradation.)
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[img] Video (AVI) (Video 10: Physically blended electrospun TEHV at 7 days of degradation.)
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[img] Video (AVI) (Video 11: Physically blended electrospun TEHV at 14 days of degradation.)
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[img] Video (AVI) (Video 12: Co-stream electrospun TEHV at 0 days of degradation.)
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[img] Video (AVI) (Video 13: Co-stream electrospun TEHV at 3 days of degradation.)
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[img] Video (AVI) (Video 14: Co-stream electrospun TEHV at 7 days of degradation.)
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[img] Video (AVI) (Video 15: Co-stream electrospun TEHV at 14 days of degradation.)
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[img] Video (AVI) (Video 16: PEUU TEHV in deionized water at 23°C at 3 hours.)
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[img] Video (AVI) (Video 17: PEUU TEHV in deionized water at 37°C at 3 hours.)
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[img] Video (AVI) (Video 18: PEUU TEHV in tap water at 37°C at 3 hours.)
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[img] Video (AVI) (Video 19: PEUU TEHV in PBS at 37°C at 3 hours.)
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[img] Video (AVI) (Video 20: PEUU TEHV in PBS with lipase at 37°C at 3 hours.)
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[img] Video (AVI) (Video 21: Nondegradable polyurethane TEHV in PBS with lipase at 37°C at 3 hours.)
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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Luketich, Samuel K.skl13@pitt.eduskl13
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWagner, William R.wagnerwr@upmc.edu
Committee MemberBorovetz, Harvey S.borovetz@pitt.edu
Committee MemberChun, Youngjaeyjchun@pitt.edu
Committee MemberD’Amore, Antonioand78@pitt.edu
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 2018 17:21
URI: http://d-scholarship.pitt.edu/id/eprint/34188

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