Biomedical Engineering Reference
In-Depth Information
8.3.2.1 The Biological Response to Well-
Deined Surface Chemistry
Well-defined surface chemistry was of great
interest to biomaterial surface science because
there was a widespread opinion within the bio-
materials community that poor biocompatibility
was related to heterogeneous surface chemistry
[72]
. It was thought that well-defined, homoge-
neous surface chemistries might provide a route
to improved biocompatibility. Although stud-
ies of the biological response to SAMs did not
lead to a general solution to the biocompatibil-
ity problem, these studies conclusively showed
that the outermost surface functional groups
that influence water wetting are directly respon-
sible for the nature and intensity of the biologi-
cal response to material surfaces. By using SAM
chemistry, all other aspects of the material and
surface could be held constant while varying
only the terminal functional group; Refs.
4, 7,
and 8
provide good summaries of what now is a
broad field of endeavor.
But exactly how, or if, terminal-functional
group chemistry influences the observed bio-
logical response to a SAM surface, over and
above the commensurate variation in water wet-
tability, is not at all clear. That is to ask, does the
chemical specificity of a particular functional
group shine through the interaction with water
and influence the biological response more than,
say, oxygen-plasma treatment to an equivalent
water contact angle? To the extent that
Figure 8.4
is true, one might not expect to observe such
chemical specificity unless the chemical func-
tionality had an extraordinary affect on local pH
or ionic strength beyond the capacity of a simple
water contact angle to measure.
There are relatively few studies that measure
a biological response to surfaces with well-
defined chemistry, incrementally sampling a full
range of surface energy that allows chemical
specificity to be isolated from surface energy
effects. A primary reason is that making a num-
ber of well-defined surfaces with incrementally
changing water wettability is experimentally
quite difficult. Early literature provided some
evidence that a particular surface functional
group—hydroxyl or carboxyl, for example—
was stimulatory to cell adhesion and prolifera-
tion
[59, 73-76]
over other functional groups.
However, it has proven difficult in subsequent
research to clearly separate cause and effect in
the cell adhesion/proliferation process, espe-
cially in the ubiquitous presence of proteins, and
by doing so unambiguously separate surface
chemistry from all other influences (such as sur-
face energy/water wettability)
[55, 77]
.
The most general rule connecting material
properties with cell-substratum compatibility
emerging from decades of focused research is that
anchorage-dependent mammalian cells strongly
favor hydrophilic surfaces
[20-22, 57, 58, 78-80]
,
as mentioned in Section
8.3.2
. The surface chem-
istry that attains this wettability seems secondary
or possibly unimportant.
Work from my laboratory has compared the
catalytic potential to induce blood plasma coag-
ulation by contacting plasma with various SAM
surfaces, finding that a basic trend in surface
energy was followed with little or no evidence
of chemical specificity. The only exception
appeared to be SAM surfaces with terminal car-
boxyl functionalities that were more activating
than anticipated based on a purely water-wetta-
bility trend
[81]
. This latter effect may well be
related to low surface pH related to -CO
2
H ioni-
zation
[82, 83]
. Surfaces bearing strong Lewis
acid/base functionalities are found to exhibit
extraordinary protein-adsorption capacity
[84]
and unique blood-contact behavior
[85]
, but this
effect is related to exceptional ion-exchange
properties of functionalities such as sulfopropyl
(A
CH
2
−
SO
3
)
, carboxymethyl (CH
2
COOH),
iminodiacetic acid (HN(CH
2
CO
2
H)
2
), quarter-
nary ammonium
(
NR
4
)
, or dimethyl aminoethyl
((CH
3
)
2
N (CH
2
CH
2
))
[86]
.
Thus it would appear from this limited sur-
vey that chemical specificity of surface func-
tional groups in the biological response to
materials can be observed only in those cases
