Platelet and endothelial adhesion on fluorosurfactant polymers designed for vascular graft modification

Abstract

A prominent failure mechanism of small-diameter expanded polytetrafluoroethylene (ePTFE) vascular grafts is platelet-mediated thrombosis. We have designed surface modification for ePTFE consisting of a self-assembling fluorosurfactant polymer (FSP) bearing biologically active ligands, including adhesive peptides and polysaccharide moieties. The goal of this biomimetic construct is to improve graft hemocompatibility by promoting rapid surface endothelialization, while minimizing platelet adhesion. Here, we present a direct comparison of platelet and endothelial cell (EC) adhesion to FSPs presenting one of three cell adhesion peptides: cyclic Arg-Gly-Asp-D-Phe-Glu (cRGD), cyclic *Cys-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys* (cRRE, *disulfide bond cyclization), linear Gly-Arg-Gly-Asp-Ser-Pro-Ala (RGD) or a polysaccharide moiety: oligomaltose (M-7), the later designed to prevent plasma protein adhesion. Measurements of soluble peptide-integrin binding indicated that cRRE exhibits the least affinity for the αIIbβ3 platelet fibrinogen receptor. Analysis of static and dynamic platelet adhesion on FSP modified surfaces demonstrated that both M-7 and cRRE promote significantly less platelet adhesion compared with RGD and cRGD FSPs, while EC adhesion was similar on all peptide FSPs and minimal on M-7 FSP. These results illustrate the potential for ligands presented in a FSP surface modification to selectively adhere ECs with limited platelet attachment.

Low Thrombogenicity Coating of Nonwoven PET Fiber Structures for Vascular Grafts

“…[22] The effectiveness of a surfactant polymer coating in preventing protein and platelets adhesion is easily measured under static conditions considered as a ''worst case'' scenario allowing the prolonged undisturbed formation of platelet-surface interactions. [7] The modification with 10% PEG solution incorporates enough hydrophilic chain molecules in the PET nonwoven grafts resulting in a seven-fold decrease platelets adhesion to the level of negative control, i.e. carbon-coated ePTFE (Figure 4), allows to conclude that the surface modification using a 10% PEG solution is sufficient in terms of anti-adhesion platelets effect.…”

“…To reduce platelet adhesion, coatings of the internal synthetic surface have included grafting polysaccharides or hydrophilic polymers to suppress platelet and protein adhesion on the luminal side, thereby increasing the graft hemocompatibility. [5][6][7][8][9][10] Previously, we developed melt-blown nonwoven PET porous fiber structures, with controllable fiber diameter and pore size allowing an optimized fiber density, size, and inter-fiber pore size for growth and attachment of vascular cells. [2,11,12] The nonwoven PET fiber structures with optimized porosity allow faster endothelialization with higher cellular confluence than commercially available polytetrafluoroethylene (PTFE) and knitted Dacron.…”

Validation that Metabolic Tumor Volume Predicts Outcome in Head and Neck Cancer

“…Unlike SUV max , MTV does not rely solely on a single point, but rather provides a quantification of metabolic tumor burden. Indeed, we previously demonstrated that increased MTV was associated with higher rates of disease progression and death (6). While our original study demonstrated promise for MTV as a risk-stratifying biomarker, the retrospective study design limits its generalizability.…”

“…Our original analysis included 85 patients that we reported on previously (6). The validation dataset in this study consisted of 83 new patients who were accrued after the original dataset.…”

New Developments in Tissue Engineering of Microvascular Prostheses

“…Fibrin has been proposed as a coating: results have been either discouraging (Mooney DJ et al 1996;Kim BS et al 1998;Wake MC et al 1996) or encouraging as regards anti-adhesive action in platelets and perlecan (Mooney DJ et al 1996;Kim BS et al 1998;Wake MC et al 1996); one article reported an elastin-like recombining protein [84,85,88]. Single peptides like RGD, cyclic RGD (Mooney DJ et al 1996;Kim BS et al 1998;Wake MC et al 1996) have also been proposed, but only in vitro studies are available (Walpoth BH et al 2007;Lord MS et al 2009;Jordan SW et al 2007;Tang C et al 2009;Larsen CC et al 2007).…”