Biomedical Engineering Reference
In-Depth Information
endgroups. The surface-modifying efficacy by SMA spacer-endgroup coordi-
nation implies a crucial contribution of manipulated albumin preoccupation
as described in Sect. 2.2.2 [78, 79].
Retardation of Fibrin Formation
According to the simplified, materials invasion-induced clotting model as
shown in Fig. 7A, the plasma coagulation cascade consists of two syn-
chronous and interrelated streams: the intrinsic and extrinsic pathways.
Briefly, the intrinsic route is initiated by a series of spontaneous reactions
between thrombogenic proteins (in turn, activation of Factors XII, XI, IX,
VIII, X, and V) and calcium (Factor IV) in plasma, which finally results
in formation of thrombin from prothrombin (Factor II). Thrombin is re-
sponsible for catalyzing the transformation of fibrinogen (Fg, Factor I) into
soluble fibrin monomers, then polymerized fibrin, finally crosslinked insolu-
ble fibrin (intermediate by activated Factor XIIIa) and thus directly causing
plasma coagulation. In comparison with the intrinsic itinerary, the extrin-
sic way is trigged by “exogenous” (other than plasma components) tissue
factors, namely thromboplastin (Factor III) that is usually released from
the tissues or cells adjacent to the bleeding injuries and, with the presence
of calcium, is capable of accelerating the transformation of thrombin from
prothrombin (with the activation of Factors VII and V in turn). Both the
intrinsic and extrinsic tracks merge at the spot of thrombin production.
Accordingly, the retardation of plasma coagulation on modified PEsU sur-
facesischaracterizedstep-by-stepwithvariousclottingtimemeasurements:
(a)
plasma recalcification time
[PRT] for the intrinsic evolution; (b)
plasma
thromboplastin
-catalyzed clotting
time
[PTT] for the extrinsic reactions; and
(c)
thrombin
-catalyzed clotting
time
[TT]. The data of plasma clotting times
are presented in Fig. 7C. As compared with un-treated PEsU materials, PRT
and PTT on modified surfaces are significantly increased, whereas little alter-
ation is observed from TT measurement. This result suggests that the advan-
tage of surface modification by MPEO-derived SMAs lies in a retardation of
thrombin formation, no matter whether for the intrinsic (by PRT) or extrin-
sic pathway (by PTT). However, if beyond the stage of thrombin formation,
namely once thrombin already appears in plasma, the formation of insolu-
ble fibrin and the consequent plasma coagulation would become inevitable.
As discussed in the last section, since vast pre-thrombin stage reactions are
catalyzed and enabled on the surface of activated platelets, the efficacy of
thrombogenic retardation by the SMAs is also crucially attributed to their
function of platelet repulsion. The results again demonstrate a functional op-
timization by the coordination of SMA spacers with their ligand endgroups,
which is also consistent with the outcomes from the platelet binding resist-
ance. At the protein level, although the proceeding of Fg-thrombin reaction
cannot be deferred by the SMAs, yet the absolute magnitude of proteinic clot-
ting Factor (typically Fg and even prothrombin) adhesion is reduced from
