000042402 001__ 42402
000042402 005__ 20240124114342.0
000042402 0247_ $$2doi$$a10.6083/bpxhc42402
000042402 037__ $$aETD
000042402 041__ $$aeng
000042402 245__ $$aThe effects of topographical micropatterning on acute thrombosis and endothelial cell (patho)physiology
000042402 260__ $$bOregon Health and Science University
000042402 269__ $$a2023-11-30
000042402 336__ $$aDissertation
000042402 502__ $$bPh.D.
000042402 502__ $$gBiomedical Engineering
000042402 520__ $$aCardiovascular disease affects nearly half of all U.S. adults and is the leading cause of death worldwide. Advanced cases are often treated through vascular grafting to bypass occluded vessels. Synthetic vascular graft materials suffer from patency complications due to thrombosis and neointimal growth impeding the materials’ long-term function for small-diameter applications. Thus, there is a critical unmet need for improved biocompatible small-diameter vascular grafts to support long-term patient outcomes and reduce re-intervention procedures. The in vitro establishment of an endothelial layer on synthetic vascular grafts has been suggested to be a solution due to the endothelial cells’ (ECs) homeostatic capabilities to prevent thrombus formation and limit immunogenicity. Therefore, vascular graft material surfaces which limit thrombosis and support EC growth and function are a significant clinical need. A surface modification that has the potential to attenuate thrombosis while promoting an endothelium is topographical micropatterning on luminal biomaterial surfaces. Topographical micropatterning is a physical modification that downregulates platelet adhesion and activation in static culture while promoting endothelial migration and function. This work provides a systematic study of the in vitro thrombogenicity of micropatterned hydrogel surfaces with varying feature sizes as well as ex vivo assessments of acute thrombogenesis on the modified grafts. Additionally, this work utilizes topographical micropatterns as a platform to induce endothelial elongation and cytoskeletal alignment to investigate changes in mechanotransduction pathways independent of blood fluid shear stress. The culmination of these findings aids in the design of novel small-diameter synthetic vascular grafts and provide insight into the mechanisms by which elongated ECs transduce an anti-inflammatory phenotype.
000042402 536__ $$oNHLBI$$cR01HL130274
000042402 536__ $$oNHLBI$$cR01HL144113
000042402 536__ $$oNIH$$cR01DE026170
000042402 536__ $$oNHLBI$$cF31HL162467
000042402 536__ $$oNHLBI$$cR01HL101972
000042402 536__ $$oNIAID$$cR01AI157037
000042402 536__ $$oAHA$$c23IAUST1019750
000042402 540__ $$fCC BY
000042402 542__ $$fIn copyright - single owner
000042402 650__ $$aThrombosis$$027034
000042402 650__ $$aEndothelial Cells$$035222
000042402 650__ $$aVascular Grafting$$039073
000042402 6531_ $$avascular graft
000042402 6531_ $$amicropatterning
000042402 691__ $$aSchool of Medicine$$041369
000042402 692__ $$aDepartment of Biomedical Engineering$$041397
000042402 7001_ $$aFallon, Meghan$$uOregon Health and Science University$$041354$$10000-0002-5868-7576
000042402 7201_ $$aHinds, Monica$$uOregon Health and Science University$$041354$$10000-0002-5267-3376$$eMentor$$7Personal
000042402 7201_ $$aBarnes, Anthony$$uOregon Health and Science University$$041354$$10000-0002-4598-9591$$eCommittee chair$$7Personal
000042402 7201_ $$aAslan, Joseph$$uOregon Health and Science University$$041354$$10000-0002-8873-0387$$eCommittee member$$7Personal
000042402 7201_ $$aNakayama, Karina$$uOregon Health and Science University$$041354$$10000-0001-5426-7446$$eCommittee member$$7Personal
000042402 7201_ $$aBertassoni, Luiz$$uOregon Health and Science University$$041354$$10000-0003-2732-8164$$eCommittee member$$7Personal
000042402 789__ $$eHas part$$w10.1115/1.4051765$$2DOI
000042402 789__ $$eIs identical to$$w10.3389/fphys.2022.983187$$2DOI
000042402 789__ $$eIs derived from$$w10.1016/j.bbrc.2021.03.129$$2DOI
000042402 792__ $$a1. Fallon ME, Mathews R, Hinds MT. In Vitro Flow Chamber Design for the Study of Endothelial Cell (Patho)Physiology. J Biomech Eng. 2022 Feb 1;144(2):020801. doi: 10.1115/1.4051765. PMID: 34254640; PMCID: PMC8628846</br>   2. Fallon ME, Le HH, Bates NM, Yao Y, Yim EKF, Hinds MT, Anderson DEJ. Hemocompatibility of micropatterned biomaterial surfaces is dependent on topographical feature size. Front Physiol. 2022 Sep 19;13:983187. doi: 10.3389/fphys.2022.983187. PMID: 36200053; PMCID: PMC9527343</br>   3. Fallon ME, Hinds MT. Single cell morphological metrics and cytoskeletal alignment regulate VCAM-1 protein expression. Biochem Biophys Res Commun. 2021 May 28;555:160-167. doi: 10.1016/j.bbrc.2021.03.129. Epub 2021 Apr 2. PMID: 33819746; PMCID: PMC8109049.
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000042402 8564_ $$yDissertation$$9cfcef791-bdf3-43f3-b5c6-49750640ac13$$s5286554$$uhttps://digitalcollections.ohsu.edu/record/42402/files/Fallon.Meghan.2024.pdf
000042402 909CO $$ooai:digitalcollections.ohsu.edu:42402$$pstudent-work
000042402 980__ $$aTheses and Dissertations
000042402 981__ $$aPublished$$b2024-01-08