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A high affinity and integrin-depende...

Chan, Bernard Pakli.

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A high affinity and integrin-dependent receptor-ligand system to enhance the adhesion of endothelial cells to synthetic surfaces.

Record Type:	Electronic resources : Monograph/item
Title/Author:	A high affinity and integrin-dependent receptor-ligand system to enhance the adhesion of endothelial cells to synthetic surfaces./
Author:	Chan, Bernard Pakli.
Description:	185 p.
Notes:	Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1969.
Contained By:	Dissertation Abstracts International65-04B.
Subject:	Engineering, Biomedical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3129063
ISBN:	0496763237

A high affinity and integrin-dependent receptor-ligand system to enhance the adhesion of endothelial cells to synthetic surfaces.
Chan, Bernard Pakli.

A high affinity and integrin-dependent receptor-ligand system to enhance the adhesion of endothelial cells to synthetic surfaces. - 185 p.

Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1969.

Thesis (Ph.D.)--Duke University, 2003.

Success of endothelialized synthetic vascular graft has been limited by poor cell retention after exposure to flow conditions. Detachment of endothelial cells (EC) involves receptor-ligand dissociation and membrane rupture. The goal of this research study was to reduce cell loss by using an approach that (1) enhances initial EC attachment, retention, and spreading on synthetic surfaces; (2) reduces the occurrence of membrane rupture; and (3) promotes normal function of EC. The previously developed "dual ligand" of fibronectin (Fn) and streptavidin(SA)-biotin was refined with a bifunctional arginine-glycine-aspartate-SA (RGD-SA) mutant that binds to integrin receptors in the EC membrane and to biotinylated albumin (b-BSA) adsorbed to the synthetic surface. Suspended EC were incubated with the RGD-SA mutant prior to cell seeding, primarily via attachment to the RGD binding site on alphavbeta3 integrin. RGD-SA incubated EC were subsequently seeded onto a surface preadsorbed with a mixture of Fn and b-BSA. EC adhesion supplemented with the RGD-SA-biotin significantly increased cell retention under flow, critical shear stresses for detachment, focal contact area, and force per bond relative to SA used with biotinylated EC. These increases were accompanied by a significant reduction in cohesive failure via cell membrane rupture. Furthermore, RGD-SA mediated adhesion enhanced phosphorylation of focal adhesion kinase (FAK) that suggested activation and clustering of integrin receptors, enhanced the flow-induced production of nitric oxide and prostacyclin, reduced the neutrophils attachment, and upregulated the expression of cytoskeleton and extracellular matrix (ECM) genes including Rho, elastin, alpha-actinin, and FAK. An in vivo model, using 1 mm internal diameter expanded polytetrafluoroethylene implanted as rat femoral artery graft, demonstrated that the dual ligand system facilitated early attachment of EC by achieving higher cell density relative to the Fn control at 1 hr of EC attachment. Analyses described in this thesis demonstrate that integrin-independent augmentation of EC adhesion using SA-biotin can be further improved through the use of a RGD-SA mutant. The refined dual ligand system represents a viable approach to rapidly seed vascular grafts.

ISBN: 0496763237Subjects--Topical Terms:

1017684
Engineering, Biomedical.

A high affinity and integrin-dependent receptor-ligand system to enhance the adhesion of endothelial cells to synthetic surfaces.
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245 1 2 $a A high affinity and integrin-dependent receptor-ligand system to enhance the adhesion of endothelial cells to synthetic surfaces.
300 $a 185 p.
500 $a Source: Dissertation Abstracts International, Volume: 65-04, Section: B, page: 1969.
500 $a Supervisor: George A. Truskey.
502 $a Thesis (Ph.D.)--Duke University, 2003.
520 $a Success of endothelialized synthetic vascular graft has been limited by poor cell retention after exposure to flow conditions. Detachment of endothelial cells (EC) involves receptor-ligand dissociation and membrane rupture. The goal of this research study was to reduce cell loss by using an approach that (1) enhances initial EC attachment, retention, and spreading on synthetic surfaces; (2) reduces the occurrence of membrane rupture; and (3) promotes normal function of EC. The previously developed "dual ligand" of fibronectin (Fn) and streptavidin(SA)-biotin was refined with a bifunctional arginine-glycine-aspartate-SA (RGD-SA) mutant that binds to integrin receptors in the EC membrane and to biotinylated albumin (b-BSA) adsorbed to the synthetic surface. Suspended EC were incubated with the RGD-SA mutant prior to cell seeding, primarily via attachment to the RGD binding site on alphavbeta3 integrin. RGD-SA incubated EC were subsequently seeded onto a surface preadsorbed with a mixture of Fn and b-BSA. EC adhesion supplemented with the RGD-SA-biotin significantly increased cell retention under flow, critical shear stresses for detachment, focal contact area, and force per bond relative to SA used with biotinylated EC. These increases were accompanied by a significant reduction in cohesive failure via cell membrane rupture. Furthermore, RGD-SA mediated adhesion enhanced phosphorylation of focal adhesion kinase (FAK) that suggested activation and clustering of integrin receptors, enhanced the flow-induced production of nitric oxide and prostacyclin, reduced the neutrophils attachment, and upregulated the expression of cytoskeleton and extracellular matrix (ECM) genes including Rho, elastin, alpha-actinin, and FAK. An in vivo model, using 1 mm internal diameter expanded polytetrafluoroethylene implanted as rat femoral artery graft, demonstrated that the dual ligand system facilitated early attachment of EC by achieving higher cell density relative to the Fn control at 1 hr of EC attachment. Analyses described in this thesis demonstrate that integrin-independent augmentation of EC adhesion using SA-biotin can be further improved through the use of a RGD-SA mutant. The refined dual ligand system represents a viable approach to rapidly seed vascular grafts.
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