Biocompatibility of cardiovascular devices - Biomaterials and Devices for the Circulatory System - page 53

fi brin coagulum deposition, and infl ammatory cell adhesion. These pro-
cesses begin almost immediately upon establishment of circulatory fl ow,
and continue over time based on the specifi c nano-structural and chemical
properties of the biomaterials which make up the device. Subsequent events
lead to the release of platelet, leukocyte, and vascular cell products that
propagate infl ammatory and mesenchymal cell infi ltration and activity. Ulti-
mately, the result of these events can lead to the pathologic development
of thrombosis, atherosclerosis, and myointimal hyperplasia limiting the
long-term effi cacy of interventional procedures.

3.2.1 Protein adsorption

Almost immediately after the establishment of circulatory fl ow, protein
adsorption to the biomaterial surfaces occurs in a manner dependent on
both the intrinsic properties of the material itself and the concentration and
diffusion coeffi cients of blood proteins. Thus, the most abundant and
mobile proteins such as albumin, immuno globulin G (IgG), low-density
lipoprotein (LDL), high-density lipoprotein (HDL), fi brinogen, and others
are among the earliest adsorbed to the device surfaces. Over the next 30-60
minutes after establishment of fl ow, however, protein adsorption continues
on the biomaterial surface as determined by the Vroman effect (Vroman,
1987). This is characterized by the dynamic interchange between proteins
initially adsorbed on the biomaterial surface with higher affi nity proteins
whose binding properties are dependent on their intrinsic three-
dimensional (3-D) conformational and electrochemical properties, as well
as the nano-structural irregularity and electrochemical activity of the bio-
material itself (Roohk et al. , 1976).
Protein-surface interactions after adsorption can further alter the surface
properties of the biomaterials, actively modulate the deposition of platelets,
infl ammatory cells, and coagulation cascade proteins, or alter the structure
of the adsorbed proteins themselves. Atomic force microscopic analysis of
fi brinogen bound to titanium, for example, has demonstrated alterations in
the conformation of bound fi brinogen in comparison to unbound fi brino-
gen (Keere et al. , 2008). Such altered structural conformations of bound
proteins demonstrate the specifi city of protein interactions with the com-
position of the biomaterial, and may suggest a proximate mechanism for
how specifi c biomaterials can differentially activate downstream host
responses.

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3.2.2 Platelet deposition

The tendency of biomaterials to adhere platelets and promote their aggre-
gation and activation prior to fi brin coagulum formation is a critical