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. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1610-1621, 2016.
authors: Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, 97239.
authors: Jeremy J
authors: JJ
authors: Glynn
authors: Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, 97239.|Department of Chemistry, Lewis & Clark College, Portland, Oregon, 97219.
authors: Casey M
authors: CM
authors: Jones
authors: Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, 97239.
authors: Deirdre E J
authors: DE
authors: Anderson
authors: Dotter Interventional Institute, Oregon Health & Science University, Portland, Oregon, 97239.
authors: Dusan
authors: D
authors: Pavcnik
authors: Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, 97239. hindsm@ohsu.edu.|Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, 97239. hindsm@ohsu.edu.|Department of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, 97006. hindsm@ohsu.edu.
authors: Monica T
authors: MT
authors: Hinds
mesh_terms: D000818:Animals; D001705:Bioprosthesis; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D012756:Sheep; D014689:Venous Insufficiency / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D055422:Venous Valves
keywords: endothelial cells; small intestinal submucosa (SIS); vascular endothelial growth factor receptor-2; venous insufficiency; venous valve