TY  - GEN
N2  - Cardiovascular 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.
DO  - 10.6083/bpxhc42402
DO  - doi
AB  - Cardiovascular 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.
AD  - Oregon Health and Science University
T1  - The effects of topographical micropatterning on acute thrombosis and endothelial cell (patho)physiology
ED  - Hinds, Monica
ED  - Barnes, Anthony
ED  - Aslan, Joseph
ED  - Nakayama, Karina
ED  - Bertassoni, Luiz
ED  - Mentor
ED  - Committee chair
ED  - Committee member
ED  - Committee member
ED  - Committee member
DA  - 2023-11-30
AU  - Fallon, Meghan
L1  - https://digitalcollections.ohsu.edu/record/42402/files/Figure%206%20Vroman%20Effect%20Confirmation.pdf
L1  - https://digitalcollections.ohsu.edu/record/42402/files/Nature%20License%20Agreement.pdf
L1  - https://digitalcollections.ohsu.edu/record/42402/files/Elsevier%20RightsLink%20Printable%20License.pdf
L1  - https://digitalcollections.ohsu.edu/record/42402/files/Fallon.Meghan.2024.pdf
PB  - Oregon Health and Science University
LA  - eng
PY  - 2023-11-30
ID  - 42402
L4  - https://digitalcollections.ohsu.edu/record/42402/files/Figure%206%20Vroman%20Effect%20Confirmation.pdf
L4  - https://digitalcollections.ohsu.edu/record/42402/files/Nature%20License%20Agreement.pdf
L4  - https://digitalcollections.ohsu.edu/record/42402/files/Elsevier%20RightsLink%20Printable%20License.pdf
L4  - https://digitalcollections.ohsu.edu/record/42402/files/Fallon.Meghan.2024.pdf
KW  - Thrombosis
KW  - Endothelial Cells
KW  - Vascular Grafting
KW  - vascular graft
KW  - micropatterning
TI  - The effects of topographical micropatterning on acute thrombosis and endothelial cell (patho)physiology
Y1  - 2023-11-30
L2  - https://digitalcollections.ohsu.edu/record/42402/files/Figure%206%20Vroman%20Effect%20Confirmation.pdf
L2  - https://digitalcollections.ohsu.edu/record/42402/files/Nature%20License%20Agreement.pdf
L2  - https://digitalcollections.ohsu.edu/record/42402/files/Elsevier%20RightsLink%20Printable%20License.pdf
L2  - https://digitalcollections.ohsu.edu/record/42402/files/Fallon.Meghan.2024.pdf
LK  - https://digitalcollections.ohsu.edu/record/42402/files/Figure%206%20Vroman%20Effect%20Confirmation.pdf
LK  - https://digitalcollections.ohsu.edu/record/42402/files/Nature%20License%20Agreement.pdf
LK  - https://digitalcollections.ohsu.edu/record/42402/files/Elsevier%20RightsLink%20Printable%20License.pdf
LK  - https://digitalcollections.ohsu.edu/record/42402/files/Fallon.Meghan.2024.pdf
UR  - https://digitalcollections.ohsu.edu/record/42402/files/Figure%206%20Vroman%20Effect%20Confirmation.pdf
UR  - https://digitalcollections.ohsu.edu/record/42402/files/Nature%20License%20Agreement.pdf
UR  - https://digitalcollections.ohsu.edu/record/42402/files/Elsevier%20RightsLink%20Printable%20License.pdf
UR  - https://digitalcollections.ohsu.edu/record/42402/files/Fallon.Meghan.2024.pdf
ER  -