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.

Advances in Engineering Venous Valves: The Pursuit of a Definite Solution for Chronic Venous Disease

“…Glynn et al explored two different approaches to promote SIS endothelialization: (i) functionalization of the material with an oriented capture antibody targeting KDR (kinase insert domain receptor), also known as vascular endothelial growth factor receptor 2, to accelerate endothelialization in situ, or (ii) in vitro pre-endothelialization of SIS valve leaflets. 93 However, high variability in between animals within groups made it difficult to draw solid conclusions. Therefore, further validation of the impact of EC seeding on SIS is needed.…”

Bioactive Anti‐Thrombotic Modification of Decellularized Matrix for Vascular Applications

“…[ 10 ] Strategies to rapidly endothelialize SIS leafl ets, either through seeding prior to implantation or by using immobilized capture antibodies to bind circulating endothelial progenitor cells, did not show signifi cant reduction in this detrimental remodeling. [ 12 ] Thus, alternative strategies to reduce thrombus formation and intimal hyperplasia on SIS are needed to broaden the utility of SIS as a vascular biomaterial.…”