In vivo assessment of two endothelialization approaches on bioprosthetic valves for the treatment of chronic deep venous insufficiency

Jeremy J. Glynn, Casey M. Jones, Deirdre E J Anderson, Dusan Pavcnik, Monica Hinds

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Chronic deep venous insufficiency is a debilitating disease with limited therapeutic interventions. A bioprosthetic venous valve could not only replace a diseased valve, but has the potential to fully integrate into the patient with a minimally invasive procedure. Previous work with valves constructed from small intestinal submucosa (SIS) showed improvements in patients' symptoms in clinical studies; however, substantial thickening of the implanted valve leaflets also occurred. As endothelial cells are key regulators of vascular homeostasis, their presence on the SIS valves may reduce the observed thickening. This work tested an off-the-shelf approach to capture circulating endothelial cells in vivo using biotinylated antikinase insert domain receptor antibodies in a suspended leaflet ovine model. The antibodies on SIS were oriented to promote cell capture and showed positive binding to endothelial cells in vitro; however, no differences were observed in leaflet thickness in vivo between antibody-modified and unmodified SIS. In an alternative approach, valves were pre-seeded with autologous endothelial cells and tested in vivo. Nearly all the implanted pre-seeded valves were patent and functioning; however, no statistical difference was observed in valve thickness with cell pre-seeding. Additional cell capture schemes or surface modifications should be examined to find an optimal method for encouraging SIS valve endothelialization to improve long-term valve function in vivo.

Original languageEnglish (US)
JournalJournal of Biomedical Materials Research - Part B Applied Biomaterials
DOIs
StateAccepted/In press - 2015

Fingerprint

Endothelial cells
Antibodies
Surface treatment

Keywords

  • Endothelial cells
  • Small intestinal submucosa (SIS)
  • Vascular endothelial growth factor receptor-2
  • Venous insufficiency
  • Venous valve

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials

Cite this

@article{6e412b313d5648b3be2db9a08d5ffd32,
title = "In vivo assessment of two endothelialization approaches on bioprosthetic valves for the treatment of chronic deep venous insufficiency",
abstract = "Chronic deep venous insufficiency is a debilitating disease with limited therapeutic interventions. A bioprosthetic venous valve could not only replace a diseased valve, but has the potential to fully integrate into the patient with a minimally invasive procedure. Previous work with valves constructed from small intestinal submucosa (SIS) showed improvements in patients' symptoms in clinical studies; however, substantial thickening of the implanted valve leaflets also occurred. As endothelial cells are key regulators of vascular homeostasis, their presence on the SIS valves may reduce the observed thickening. This work tested an off-the-shelf approach to capture circulating endothelial cells in vivo using biotinylated antikinase insert domain receptor antibodies in a suspended leaflet ovine model. The antibodies on SIS were oriented to promote cell capture and showed positive binding to endothelial cells in vitro; however, no differences were observed in leaflet thickness in vivo between antibody-modified and unmodified SIS. In an alternative approach, valves were pre-seeded with autologous endothelial cells and tested in vivo. Nearly all the implanted pre-seeded valves were patent and functioning; however, no statistical difference was observed in valve thickness with cell pre-seeding. Additional cell capture schemes or surface modifications should be examined to find an optimal method for encouraging SIS valve endothelialization to improve long-term valve function in vivo.",
keywords = "Endothelial cells, Small intestinal submucosa (SIS), Vascular endothelial growth factor receptor-2, Venous insufficiency, Venous valve",
author = "Glynn, {Jeremy J.} and Jones, {Casey M.} and Anderson, {Deirdre E J} and Dusan Pavcnik and Monica Hinds",
year = "2015",
doi = "10.1002/jbm.b.33507",
language = "English (US)",
journal = "Journal of Biomedical Materials Research - Part B Applied Biomaterials",
issn = "1552-4973",
publisher = "Heterocorporation",

}

TY - JOUR

T1 - In vivo assessment of two endothelialization approaches on bioprosthetic valves for the treatment of chronic deep venous insufficiency

AU - Glynn, Jeremy J.

AU - Jones, Casey M.

AU - Anderson, Deirdre E J

AU - Pavcnik, Dusan

AU - Hinds, Monica

PY - 2015

Y1 - 2015

N2 - Chronic deep venous insufficiency is a debilitating disease with limited therapeutic interventions. A bioprosthetic venous valve could not only replace a diseased valve, but has the potential to fully integrate into the patient with a minimally invasive procedure. Previous work with valves constructed from small intestinal submucosa (SIS) showed improvements in patients' symptoms in clinical studies; however, substantial thickening of the implanted valve leaflets also occurred. As endothelial cells are key regulators of vascular homeostasis, their presence on the SIS valves may reduce the observed thickening. This work tested an off-the-shelf approach to capture circulating endothelial cells in vivo using biotinylated antikinase insert domain receptor antibodies in a suspended leaflet ovine model. The antibodies on SIS were oriented to promote cell capture and showed positive binding to endothelial cells in vitro; however, no differences were observed in leaflet thickness in vivo between antibody-modified and unmodified SIS. In an alternative approach, valves were pre-seeded with autologous endothelial cells and tested in vivo. Nearly all the implanted pre-seeded valves were patent and functioning; however, no statistical difference was observed in valve thickness with cell pre-seeding. Additional cell capture schemes or surface modifications should be examined to find an optimal method for encouraging SIS valve endothelialization to improve long-term valve function in vivo.

AB - Chronic deep venous insufficiency is a debilitating disease with limited therapeutic interventions. A bioprosthetic venous valve could not only replace a diseased valve, but has the potential to fully integrate into the patient with a minimally invasive procedure. Previous work with valves constructed from small intestinal submucosa (SIS) showed improvements in patients' symptoms in clinical studies; however, substantial thickening of the implanted valve leaflets also occurred. As endothelial cells are key regulators of vascular homeostasis, their presence on the SIS valves may reduce the observed thickening. This work tested an off-the-shelf approach to capture circulating endothelial cells in vivo using biotinylated antikinase insert domain receptor antibodies in a suspended leaflet ovine model. The antibodies on SIS were oriented to promote cell capture and showed positive binding to endothelial cells in vitro; however, no differences were observed in leaflet thickness in vivo between antibody-modified and unmodified SIS. In an alternative approach, valves were pre-seeded with autologous endothelial cells and tested in vivo. Nearly all the implanted pre-seeded valves were patent and functioning; however, no statistical difference was observed in valve thickness with cell pre-seeding. Additional cell capture schemes or surface modifications should be examined to find an optimal method for encouraging SIS valve endothelialization to improve long-term valve function in vivo.

KW - Endothelial cells

KW - Small intestinal submucosa (SIS)

KW - Vascular endothelial growth factor receptor-2

KW - Venous insufficiency

KW - Venous valve

UR - http://www.scopus.com/inward/record.url?scp=84940706479&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940706479&partnerID=8YFLogxK

U2 - 10.1002/jbm.b.33507

DO - 10.1002/jbm.b.33507

M3 - Article

JO - Journal of Biomedical Materials Research - Part B Applied Biomaterials

JF - Journal of Biomedical Materials Research - Part B Applied Biomaterials

SN - 1552-4973

ER -