Biomedical Engineering Reference
In-Depth Information
necessarily predict. In this case, the calibration
might relate the biological response to the num-
ber of immobilized biomimetic groups per unit
area, perhaps as measured by radiometry, for
example. Alternatively, net enzymic activity of
the surface might be correlated with the biologi-
cal response.
activating surfaces together with other proteins,
constituting a reaction complex that ultimately
produces the principle activated enzyme FXIIa
from FXII. It is thus essential to understand the
adsorption properties of FXII and FXIIa toward
designing surfaces that do not induce blood
coagulation. Likewise, understanding protein
adsorption from the plasma milieu is crucial
to understanding how FXII adsorbs to surfaces
in competition with more than a thousand
other proteins that constitute the blood plasma
proteome
[18]
.
8.4.5 An Example
The following is an example relating wettabil-
ity of engineered surfaces to the adsorption
of blood factor XII and the related activation
of blood plasma coagulation. This example is
based on methods and results reported in Refs.
81, 142, and 143
and illustrates some of the prin-
ciples discussed in the preceding section, show-
ing how surface modification can be related to
a complex biological response to these surfaces.
Some brief background about blood coagula-
tion and protein adsorption is helpful as an
introduction.
8.4.5.2 Adsorption Mapping
There are many methods of measuring protein
adsorption from purified solutions of a single
protein, but few are designed to measure protein
adsorption from binary solutions, let alone a
mixture of more than a thousand proteins
[16]
. A
modification of standard surface thermodynamics
was invented that correlates protein adsorption
to the water wettability of an adsorbent surface,
which is equally applicable to purified protein
solutions and biological milieu such as blood
plasma
[142]
. This graphical method was termed
adsorption mapping
and has been applied to the
blood coagulation problem
[20-22, 81, 143]
.
Briefly, an adsorption map is the plot of the
difference in adhesion tension
8.4.5.1 Contact Activation of Blood
Coagulation
Blood coagulates in contact with all biomaterials
[28]
. The exact reasons for this are not entirely
known. Thus, the contact activation of blood
coagulation problem has been, and continues
to be, an active area of research in biomaterials
surface science. Understanding the molecular
details of contact activation is crucial to devel-
opment of advanced cardiovascular biomateri-
als that occupy the upper strata of the healthcare
pyramid diagrammed in
Figure 8.1
.
An important discovery made in the late
1960s (see Refs.
144-148
and citations therein for
historical reviews) was that a particular protein,
blood factor XII, sometimes referred to as
Hage-
man factor
or
FXII
, became activated by contact
with hydrophilic surfaces, producing an enzyme
(or possibly enzymes) that potentiate a cascade
of biochemical reactions that ultimately causes
blood plasma to coagulate or clot
[28]
. It was
postulated that FXII adsorbs or assembles onto
τ
′
−
τ
O
against
τ
O
, where
τ
′
= γ
LV
COS θ
′
and
τ
O
=
γ
LV
COS θ
O
. Adhe-
sion tension measures the strength of adhesion
of a droplet of fluid to a test surface in mJ/m
2
exhibiting an advancing or receding contact
angle
θ
on that surface. The liquid-vapor (lv)
interfacial tensions
γ
LV
are measured separately
from
θ
. The prime superscript denotes a solution
containing a protein or many proteins compris-
ing a milieu of interest whereas the “o” super-
script denotes pure buffer solution containing
no proteins. Thus, the difference
τ
′
−
τ
O
is an
adsorption index that measures the effect of pro-
tein adsorption on surface wetting, with posi-
tive values corresponding to protein-adsorbent
surfaces and zero or negative values corre-
sponding to surfaces that do not adsorb protein
