Biomedical Engineering Reference
In-Depth Information
a ''conditioning film'' of molecules (often proteins) that
adsorbs first to the surface. The bacteria stick to this
conditioning film and begin to exude a gelatinous slime
layer (the biofilm) that aids in their protection from
external agents (for example, antibiotics). Such layers are
particularly troublesome in devices such as urinary
catheters and endotracheal tubes. However, they also
form on vascular grafts, hip joint prostheses, heart valves,
and other long-term implants where they can stimulate
significant inflammatory reaction to the infected device.
If the conditioning film can be inhibited, bacterial ad-
hesion and biofilm formation can also be reduced. NFSs
offer this possibility.
NFSs have medical and biotechnology uses as blood-
compatible materials (where they may resist fibrinogen
adsorption and platelet attachment), implanted devices,
urinary catheters, diagnostic assays, biosensors, affinity
separations, microchannel flow devices, intravenous sy-
ringes and tubing, and nonmedical uses as biofouling-
resistant heat exchangers and ship bottoms. It is important
to note that many of these uses involve
in vivo
implants or
extracorporeal devices, and many others involve
in vitro
diagnostic assays, sensors, and affinity separations. As well
as having considerable medical and economic importance,
NFSs offer important experimental and theoretical in-
sights into one of the important phenomena in bio-
materials science, protein adsorption. Hence, they have
been the subject of many investigations. Aspects of
NFSs are addressed in Section 3.1.5 and 3.2.14.
The majority of the literature on non-fouling surfaces
focuses
(
Horbett and Brash, 1987, 1995; Hoffman, 1986
).
The driving force for this action is most likely the
unfolding of the protein on the surface, accompanied
by release of many hydrophobically structured water
molecules from the interface, leading to a large
entropy gain for the system (
Hoffman, 1999
). Note
that adsorbed proteins can be displaced from the
surface by solution phase proteins (Brash
et al
., 1974).
It is also well known that at low ionic strengths
cationic proteins bind to anionic surfaces and
anionic proteins bind to cationic surfaces (
Hoffman,
1999; Horbett and Hoffman, 1975
). The major
thermodynamic driving force for these actions is
a combination of ion-ion coulombic interactions,
accompanied by an entropy gain due to the release of
counterions along with their waters of hydration.
However, these interactions are diminished at
physiologic conditions by shielding of the protein
ionic groups at the 0.15 N ionic strength (
Horbett
and Hoffman, 1975
). Still, lysozyme, a highly
charged cationic protein at physiologic pH, strongly
binds to hydrogel contact lenses containing anionic
monomers (see Bohnert
et al.,
1988 for discussion of
class IV contact lenses).
It has been a common observation that proteins tend
to adsorb in monolayers, i.e., proteins do not adsorb
nonspecifically onto their own monolayers (
Horbett,
1993
). This is probably due to retention of hydration
water by the adsorbed protein molecules, preventing
close interactions of the protein
molecules in solution with the adsorbed protein
molecules. In fact, adsorbed protein films are, in
themselves, reasonable NFSs with regard to other
proteins (but not necessarily to cells).
Many studies have been carried out on surfaces
coated with physically or chemically immobilized
PEG, and a conclusion was reached that the PEG
molecular weight should be above a minimum of
ca.2000 in order to provide good protein repulsion
(Mori
et al.
, 1983;
Gombotz
et al.
, 1991; Merrill,
1992
). This seems to be the case whether PEG is
chemically bound as a side chain of a polymer that is
grafted to the surface (Mori
et al.
, 1983), is bound by
one end to the surface (Gombotz
et al.,
1991;
Merrill, 1992
), or is incorporated as segments in
a cross-linked network (
Merrill, 1992
). The mini-
mum MW was found to be ca. 500-2000, depending
on packing density (Mori
et al.
, 1983;
Gombotz
et al.
, 1991; Merrill, 1992
).
The mechanism of protein resistance by the PEG
surfaces may due to be a combination of factors,
including the resistance of the polymer coil to
compression due to its desire to retain the volume
of a random coil (called ''entropic repulsion'' or
on
surfaces
containing
the
relatively
simple
polymer PEG:
ð
—CH
2
CH
2
O—
Þ
n
When
n
is in the range of 15-3500 (molecular weights of
approximately 400-100,000), the PEG designation is
used. When molecular weights are greater than 100,000,
the molecule is commonly referred to as PEO. Where
n
is
in the range of 2-15, the term oligo(ethylene glycol)
(oEG) is often used. An interesting article on the origins
of the use of PEG to enhance the circulation time of
proteins in the body has recently been published by Davis
(2002). Other natural and synthetic polymers besides
PEG show nonfouling behavior, and they will also be
discussed in this section.
Background
The published literature on protein and cell interactions
with biomaterial surfaces has grown significantly in the
past 30 years, and the following concepts have emerged:
It is well established that hydrophobic surfaces have
a strong tendency to adsorb proteins irreversibly
