Integrated Biomaterials Science

Structure and Properties of Polymeric Materials 55
Hydrosoluble carbodiimides and Woodward’s reagent are often and
more efficiently employed to activate carboxy groups belonging both to
heparin and to the matrix, while bifunctional reagents like glutaraldehyde
or acyl chlorides of dicarboxylic acids possess the further advantage of
acting as “spacing agents” of the heparin from the solid surface, so
guaranteeing the anticoagulant molecule higher mobility and conformational
freedom (Marconi et al., 1993).
Different types of limitations and problems are involved in the
covalent immobilization of heparin. Some are of a technical and practical
nature, like the possibility of degradation during the immobilization procedure,
while some difficulties are due to the fact that heparin dissolves only
in water and, at a lower degree, in formamide. Other difficulties involve
functional aspects, like the drastic activity decrease of bonded heparin with
respect to the native one, due to its consequent lower mobility in the
aqueous medium and to its reduced accessibility from the large molecules
(thrombin and ATIII) with which it must interact.
In order to minimize this latter drawback, heparin was bonded to
hydrophilic matrices able to swell in water, like sepharose, poly(vinylalcohol),
or poly(hydroxyethyl-methacrylate) (Miura et al., 1980). Since,
however, these types of polymers usually possess poor mechanical properties,
they are deposited by casting onto a sufficiently strong material, such
as poly(urethane), and then (before reaction with heparin) crosslinked, to
make them water-insoluble. A widely utilized methodology for increasing
mobility and accessibility of heparin employs its bonding to suitable
“spacers,” i.e., to high molecular weight hydrophilic molecules, which
enables it to get out of the polymer surface and lean forward into the
aqueous phase. In particular, poly(ethyleneoxide) (PEO) of different molecular
weight was used for this purpose, for example onto poly(urethane)
matrices (Han et al., 1989).
2.4.2.2. Surface Modifications by Different Hemocompatibility Enhancers
It has been noted that, also in the absence of heparinization treatment,
segmented poly(urethane) surfaces containing PEO show a much lower
platelet adhesion and a decreased adsorption of blood proteins like albumin
and fibrinogen. Therefore, this procedure was extended to other polymers
(e.g., of acrylic type) and the aforesaid good achievements were confirmed.
This behavior was attributed to an improved molecular motion of the long
hydrated chains of PEO, and to the thermodynamic repulsive forces
deriving from the consequent excluded volume.
As a result of the great success obtained by pyrolytic carbon in the
fabrication of components of cardiac valves, this technology was extended