Impact of parallel micro-engineered stent grooves on endothelial cell migration, proliferation, and function: An in vivo correlation study of the healing response in the coronary swine model

Eugene A Sprague, Fermin Tio, Shah-hinan Ahmed, Juan F. Granada, Steven R Bailey

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: Stent luminal surface characteristics influence surface endothelialization. We hypothesize that luminal stent microgrooves created in the direction of coronary flow accelerate endothelial cell migration, resulting in lower levels of neointimal formation. Methods and Results: Surface coverage efficiency was evaluated in vitro by allowing human aortic endothelial cells (HAEC) to migrate onto microgrooved (G) or smooth (NG) surfaces. HAEC functionality was assessed by proliferation rate, apoptosis rate, nitric oxide production, and inflammatory markers TNF-α and VCAM-1 expression. Early endothelialization and restenosis studies were performed using the porcine coronary injury model. Stainless steel stents of identical design with (GS) and without (NGS) luminal microgrooves were used. The commercially available Multi-Link Vision (MLVS) stent of identical design was used as a control. The degree of GS and NGS surface endothelialization was compared at 3 days. Biocompatibility and tissue response outcomes were evaluated at 28 days. The in vitro study demonstrated that at 7 days the presence of surface microgrooves increased HAEC migration distance >2-fold. Cell proliferation rate and nitric oxide production were increased and apoptosis rate was decreased. There was no difference in inflammatory marker expression. At 3 days, coronary artery stent endothelialization was significantly increased in GS compared with NGS (81.3% versus 67.5%, P=0.0002). At 28 days, GS exhibited lower neointimal thickness compared with either NGS (21.1%, P=0.011) or MLVS (40.8%, P=0.014). Conclusions: Parallel microgrooves on coronary stent luminal surfaces promote endothelial cell migration and positively influence endothelial cell function, resulting in decreased neointimal formation in the porcine coronary injury model.

Original languageEnglish (US)
Pages (from-to)499-507
Number of pages9
JournalCirculation: Cardiovascular Interventions
Volume5
Issue number4
DOIs
StatePublished - Aug 2012

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Cell Movement
Stents
Swine
Endothelial Cells
Cell Proliferation
Nitric Oxide
Apoptosis
Vascular Cell Adhesion Molecule-1
Stainless Steel
Wounds and Injuries
Coronary Vessels
In Vitro Techniques

Keywords

  • Coronary stent
  • Endothelial function
  • Endothelialization
  • Neointimal hyperplasia
  • Restenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{a0b6cb31d53b452788671ff6958ce0cb,
title = "Impact of parallel micro-engineered stent grooves on endothelial cell migration, proliferation, and function: An in vivo correlation study of the healing response in the coronary swine model",
abstract = "Background: Stent luminal surface characteristics influence surface endothelialization. We hypothesize that luminal stent microgrooves created in the direction of coronary flow accelerate endothelial cell migration, resulting in lower levels of neointimal formation. Methods and Results: Surface coverage efficiency was evaluated in vitro by allowing human aortic endothelial cells (HAEC) to migrate onto microgrooved (G) or smooth (NG) surfaces. HAEC functionality was assessed by proliferation rate, apoptosis rate, nitric oxide production, and inflammatory markers TNF-α and VCAM-1 expression. Early endothelialization and restenosis studies were performed using the porcine coronary injury model. Stainless steel stents of identical design with (GS) and without (NGS) luminal microgrooves were used. The commercially available Multi-Link Vision (MLVS) stent of identical design was used as a control. The degree of GS and NGS surface endothelialization was compared at 3 days. Biocompatibility and tissue response outcomes were evaluated at 28 days. The in vitro study demonstrated that at 7 days the presence of surface microgrooves increased HAEC migration distance >2-fold. Cell proliferation rate and nitric oxide production were increased and apoptosis rate was decreased. There was no difference in inflammatory marker expression. At 3 days, coronary artery stent endothelialization was significantly increased in GS compared with NGS (81.3{\%} versus 67.5{\%}, P=0.0002). At 28 days, GS exhibited lower neointimal thickness compared with either NGS (21.1{\%}, P=0.011) or MLVS (40.8{\%}, P=0.014). Conclusions: Parallel microgrooves on coronary stent luminal surfaces promote endothelial cell migration and positively influence endothelial cell function, resulting in decreased neointimal formation in the porcine coronary injury model.",
keywords = "Coronary stent, Endothelial function, Endothelialization, Neointimal hyperplasia, Restenosis",
author = "Sprague, {Eugene A} and Fermin Tio and Shah-hinan Ahmed and Granada, {Juan F.} and Bailey, {Steven R}",
year = "2012",
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doi = "10.1161/CIRCINTERVENTIONS.111.967901",
language = "English (US)",
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pages = "499--507",
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TY - JOUR

T1 - Impact of parallel micro-engineered stent grooves on endothelial cell migration, proliferation, and function

T2 - An in vivo correlation study of the healing response in the coronary swine model

AU - Sprague, Eugene A

AU - Tio, Fermin

AU - Ahmed, Shah-hinan

AU - Granada, Juan F.

AU - Bailey, Steven R

PY - 2012/8

Y1 - 2012/8

N2 - Background: Stent luminal surface characteristics influence surface endothelialization. We hypothesize that luminal stent microgrooves created in the direction of coronary flow accelerate endothelial cell migration, resulting in lower levels of neointimal formation. Methods and Results: Surface coverage efficiency was evaluated in vitro by allowing human aortic endothelial cells (HAEC) to migrate onto microgrooved (G) or smooth (NG) surfaces. HAEC functionality was assessed by proliferation rate, apoptosis rate, nitric oxide production, and inflammatory markers TNF-α and VCAM-1 expression. Early endothelialization and restenosis studies were performed using the porcine coronary injury model. Stainless steel stents of identical design with (GS) and without (NGS) luminal microgrooves were used. The commercially available Multi-Link Vision (MLVS) stent of identical design was used as a control. The degree of GS and NGS surface endothelialization was compared at 3 days. Biocompatibility and tissue response outcomes were evaluated at 28 days. The in vitro study demonstrated that at 7 days the presence of surface microgrooves increased HAEC migration distance >2-fold. Cell proliferation rate and nitric oxide production were increased and apoptosis rate was decreased. There was no difference in inflammatory marker expression. At 3 days, coronary artery stent endothelialization was significantly increased in GS compared with NGS (81.3% versus 67.5%, P=0.0002). At 28 days, GS exhibited lower neointimal thickness compared with either NGS (21.1%, P=0.011) or MLVS (40.8%, P=0.014). Conclusions: Parallel microgrooves on coronary stent luminal surfaces promote endothelial cell migration and positively influence endothelial cell function, resulting in decreased neointimal formation in the porcine coronary injury model.

AB - Background: Stent luminal surface characteristics influence surface endothelialization. We hypothesize that luminal stent microgrooves created in the direction of coronary flow accelerate endothelial cell migration, resulting in lower levels of neointimal formation. Methods and Results: Surface coverage efficiency was evaluated in vitro by allowing human aortic endothelial cells (HAEC) to migrate onto microgrooved (G) or smooth (NG) surfaces. HAEC functionality was assessed by proliferation rate, apoptosis rate, nitric oxide production, and inflammatory markers TNF-α and VCAM-1 expression. Early endothelialization and restenosis studies were performed using the porcine coronary injury model. Stainless steel stents of identical design with (GS) and without (NGS) luminal microgrooves were used. The commercially available Multi-Link Vision (MLVS) stent of identical design was used as a control. The degree of GS and NGS surface endothelialization was compared at 3 days. Biocompatibility and tissue response outcomes were evaluated at 28 days. The in vitro study demonstrated that at 7 days the presence of surface microgrooves increased HAEC migration distance >2-fold. Cell proliferation rate and nitric oxide production were increased and apoptosis rate was decreased. There was no difference in inflammatory marker expression. At 3 days, coronary artery stent endothelialization was significantly increased in GS compared with NGS (81.3% versus 67.5%, P=0.0002). At 28 days, GS exhibited lower neointimal thickness compared with either NGS (21.1%, P=0.011) or MLVS (40.8%, P=0.014). Conclusions: Parallel microgrooves on coronary stent luminal surfaces promote endothelial cell migration and positively influence endothelial cell function, resulting in decreased neointimal formation in the porcine coronary injury model.

KW - Coronary stent

KW - Endothelial function

KW - Endothelialization

KW - Neointimal hyperplasia

KW - Restenosis

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DO - 10.1161/CIRCINTERVENTIONS.111.967901

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