Biomedical Engineering Reference
In-Depth Information
3.2.2.3 Hemostatic Mechanism
Protonated amine groups of chitosan can attract negatively charged residues on RBC
membranes, causing strong hemagglutination [103-106]. Chitosan also adsorbed fibrino-
gen and plasma proteins, enhancing platelet aggregation [107,108].
On the other hand, polyphosphate specifically activated the contact pathway, which
shortened both the time lag for initial thrombin generation and the time to peak thrombin
generation. Polyphosphate in the dressing would accelerate the production of sufficient
amounts of thrombin to support earlier fibrin generation. At the same time, chitosan would
recruit RBCs to enlarge and solidify the growing thrombus, leading to a stable clot that
stops bleeding. While chitosan containing 6.7% w/w and 10% w/w PP accelerated whole-
blood clotting compared to chitosan, the benefits of PP were negated at higher concentra-
tions (15% w/w). One possible explanation is the following: At lower PP levels, the
accelerated thrombin generation and resultant fibrin formation could trap more RBCs that
were aggregated on chitosan into the clot. However, at higher PP levels, free cationic amine
groups of chitosan were reduced to an extent that significantly reduced its ability to elec-
trostatically attract and bring RBCs in close proximity with fibrin. The dressing's ability to
adhere RBCs was significant, not only because RBCs provided bulk to the clot, but more
importantly because adhered RBCs have been shown to deform and expose procoagulant
phospholipids (phosphatidylserine) on the membrane surface, similar to activated plate-
lets [109]. These procoagulant sites allowed the assembly of prothrombinase complexes
that catalyze the conversion of prothrombin to thrombin [110].
PP may be required above a critical level to significantly shorten the lag time for initial
thrombin generation and lead to faster platelet activation and adhesion [109]. Alternatively,
complexes containing different proportions of PP may have different surface charge distri-
butions, which affected electrostatic interactions between plasma proteins and in turn
affected platelet binding and subsequent activation [110].
The type of polyphosphate polymer in the complex may also affect hemostatic activity.
Chitosan-10% PP45 induced significantly faster thrombin generation than chitosan, while
chitosan-10% PP65 dressings containing the same amount of polyphosphate did not.
Since there were a greater number of polyphosphate chains (albeit 20 units shorter) in the
chitosan-10% PP45 complex compared with the chitosan-10% PP65 complex, the frequency
of complexed segments, rather than the size of complexed segments, may be more critical
for increasing the number of procoagulant sites on the material, which accelerated coagu-
lation cascade turnover and led to faster thrombin formation.
3.2.3 blood Compatibility
In recent years, various biomaterials that are natural or synthetic polymeric materials have
been widely used for manufactory biomedical applications such as artificial organs, medi-
cal devices, and disposable clinical apparatus [111]. These include vascular prostheses,
blood pumps, artificial kidneys, heart valves, pacemaker lead wire insulation, intra-aortic
balloons, artificial hearts, dialyzers, and plasma separators, which could be used in contact
with blood. However, the polymers currently used are conventional materials, such as cel-
lulose, chitosan, poly(tetrafluoroethylene) (PTFE), poly(vinyl chloride) (PVC), segmented
polyetherurethane (SPU), polyethylene (PE), silicone rubber (SR), nylon, and polysulfone
(PSf). When in direct contact with blood, they are still prone to initiating the formation of
clots, as platelets and other components of the blood coagulation system are activated. It is
well known that the formation of a thrombus is dependent on the behavior of platelets at
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