Biocompatibility of cardiovascular devices - Biomaterials and Devices for the Circulatory System - page 54

component to the biocompatibility of cardiovascular devices. Clearly,
thrombus formation not only leads to acute device failures as seen in
conduit thromboses, but also serves as a scaffold for mesenchymal and
infl ammatory cell infi ltration prior to the formation of atherosclerotic
plaques and myointimal lesions.
After intimal injury, platelet adherence in vivo occurs via binding of the
platelet surface glycoprotein (GP) receptor complexes Ia/IIa and Ib/IX/V
to exposed subendothelial extracellular matrix (ECM) proteins like colla-
gen or von Willebrand factor (vWF) bound to collagen (Jennings, 2009).
Interactions of these glycoproteins with vWF bound to the exposed suben-
dothelium or to endothelial cell (EC) surfaces activates platelets and causes
the release of -thromboglobulin,

thrombospondin, vWF and fi bronectin, and increases the local concentra-
tions of serotonin, epinephrine, and adenosine diphosphate (ADP), among
others. This degranulation serves to propagate platelet aggregation and
activation. The formation of the prothrombinase complex on activated
platelets mediated by the extrinsic coagulation pathway facilitates thrombin
formation and subsequent fi brin generation (Jennings, 2009). Other factors
released, including platelet derived growth factor (PDGF), platelet factor
4, and thromboxane A2, act to further modulate the subsequent infl amma-
tory response, as well the meschenchymal cell infi ltrative response. The
impact of these glycoproteins on direct adherence of platelets to biomate-
rial surfaces remain unclear. However, the interaction of GPIIb/IIIa with
the adsorbed RGD peptide sequences of fi brinogen and fi bronectin appears
to be an important mediator of platelet deposition onto artifi cial surfaces,
and evidence demonstrates a direct correlation of fi brinogen adsorption to
platelet adherence (Roohk et al. , 1976; Nagai et al. , 1993; Beumer et al. , 1994;
Greisler et al. , 1989b).
Platelet deposition contributes to device failure not only by the formation
of an occlusive or lumen narrowing thrombus, but also by inducing potential
alterations in drug release kinetics from drug-carrying polymer coatings as
utilized in drug eluting stents (discussed below). Drug deposition within
developed thrombi have been shown to alter local drug concentrations,
which may have the effect of limiting or increasing their bioavailability and
effi cacy (Balakrishnan et al. , 2008).

α -granule products such as fi brinogen, β

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3.2.3 Infl ammation and immunology

The infl ammatory and immunologic responses to implanted cardiovascular
devices can lead to direct tissue damage mediated by leukocytes and their
released products, and may contribute to the initiation, remodeling, and
progression of myointimal hyperplasia. Additionally, immunocompatibility
is an obvious concern in the development of tissue patches and allogeneic