Tissue responses to implanted materials - Biomaterials and Devices for the Circulatory System - page 11

Another potential allergen is ethylene oxide gas. It is used in the sterilisa-
tion of DES. DES have been linked to a wide variety of hypersensitivity
responses. The most sinister of these responses is the often fatal coronary
thrombosis that extends into the stent. Histological examination on autopsy
demonstrates intrastent eosinophilic infi ltrates (Honari et al. , 2008). This
suggests that more precise assessments of patients susceptible to hypersen-
sitivity reactions and the use of agents that suppress such reactions may
play a role in improving outcomes in patients receiving drug-eluting coro-
nary stents (Chen et al. , 2009).

1.5 Thromboembolic complications

Thrombus formation on an artifi cial device is governed by Virchow's triad.
Surface characteristics of the prosthesis, blood fl ow and characteristics of
the blood constituents of the host are all determinants of potential throm-
bogenicity. As will be discussed in biofi lm formation, a variety of circulating
extracellular proteins including serum albumin, fi brinogen, collagen and
fi bronectin adhere to artifi cial surfaces once introduced within the blood-
stream (Reid, 1999). Synchronously a wide variety of cells may adhere to
these surfaces either directly or via protein interlinking and in turn secrete
factors that will initiate platelet activation and adherence. In addition
changes in the structure of adhered protein macromolecules may lead to
platelet adhesion via direct binding to surface proteins GP Ib and GP IIb/
IIIa (Horbett, 1993). Platelet adhesion is followed by further aggregation
leading either to clot formation or breakdown of thrombus via fi brinolysis
(via activation of coagulation cascades, description of which escapes the
scope of this review).
Direct mechanical-induced damage, artifi cial surfaces (mechanical pros-
theses) and local disruption of normal fl ow patterns may induce damage to
circulating blood elements including platelets, in the case of prosthetic heart
valves. Mean turbulent shear stress in excess of 200 dynes/cm 2 may be created
during the major portion of systole and diastole (Yoganathan, 2000). Notably,
in the vicinity of mechanical aortic heart valves peak shear stresses can easily
exceed 1500 dynes/cm 2 . Within tubular vascular grafts platelet adherence and
subsequent coagulation pathway activation may lead to inner graft coating
with a layer of fi brin, platelet debris and trapped red blood cells described
as pseudointimal hyperplasia (Greisler, 1991). Flow occlusion may result in
graft failure, thus jeopardising viability of perfused organs or even recipient
life. Engineering of less thrombogenic surfaces is an active fi eld of research.
Seeding with endothelial cells, photopolymerisation, plasma-gas coatings and
antisense genetics are some the experimental approaches that have been
reported to date (Greisler, 1991). Interestingly examination of explanted
left ventricular assist devices has identifi ed the pivotal role of pluripotent

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