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“Attractive” Treatment for Abdominal Aortic Aneurysm: Magnetic Localization of Silk-Iron Packaged Extracellular Vesicles

Marini, Ande (2025) “Attractive” Treatment for Abdominal Aortic Aneurysm: Magnetic Localization of Silk-Iron Packaged Extracellular Vesicles. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Abdominal aortic aneurysm (AAA) is a dilatation of the distal aorta to a diameter 50% or more of its normal size of about 2 cm. Treatment of AAAs requires either open surgery or endovascular repair, which is not clinically recommended until the diameter of the aneurysm has reached a critical threshold (taken as 5.5 cm in men or 5.0 cm in women). Thus, patients with AAA sized below this threshold are monitored until they are eligible for surgery; however, there have been cases where the AAA ruptures before this surgical threshold can be met, indicating a clear need for a treatment for small AAAs.
Previous work in our lab has utilized adipose tissue derived mesenchymal stem cells (AT MSCs) to locally treat AAA in vivo, preserving elastic fibers and slowing aneurysm expansion. This dissertation presents an extension of that previous work, creating a delivery system for therapeutic extracellular vesicles (MSC-EVs) secreted by AT MSCs. Our delivery system incorporated the biocompatibility of regenerated silk fibroin (RSF), the magnetic moveability of iron oxide nanoparticles (IONPs), and the regenerative nature of MSC-EVs to create silk-iron packaged extracellular vesicles (SIPEs). Using this system, we tested the ability to magnetically localize the microparticles and release their encapsulated MSC-EVs to exert their regenerative effects.
Magnetic moveability was tested through solution and within a polymerizing hydrogel, and MSC-EV release and uptake were demonstrated using 3D SMC-seeded fibrin gel constructs. MSC-
v
EVs and SIPEs were tested in vitro for proteolytic activity and stimulation of elastin and collagen synthesis. For in vivo analysis, testing was performed in an AAA mouse model (and preliminarily a AAA rat model) wherein SIPEs were delivered locally to the site of the aneurysm to assess their potential regenerative effects.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Marini, Andeaxg5@pitt.eduaxg5
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWeinbaum, Justin S.juw51@pitt.edujuw510000-0002-0626-6083
Committee MemberBedewy, Mostafambedewy@pitt.edumbedewy0000-0003-4182-7533
Committee MemberChaer, Rabih A.chaerra@upmc.edu0009-0003-5170-573X
Committee MemberDiLeo, Morgan V.morgandileo@pitt.edumod80000-0002-8949-8305
Committee MemberMarra, Kacey G.marrak@upmc.edukgm50000-0002-8437-4864
Committee MemberVorp, David A.vorp@pitt.eduvorp0000-0002-6467-2151
Date: 7 January 2025
Date Type: Publication
Defense Date: 11 November 2024
Approval Date: 7 January 2025
Submission Date: 4 December 2024
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 366
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: Abdominal Aortic Aneurysm, Extracellular Vesicles, Cardiovascular Disease, Regenerative Medicine, Drug Delivery, Microparticles, Iron Oxide Nanoparticles, Silk Fibroin, Magnetic
Date Deposited: 02 Apr 2025 21:32
Last Modified: 02 Apr 2025 21:33
URI: http://d-scholarship.pitt.edu/id/eprint/47170

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