Biomedical Engineering Reference
In-Depth Information
is generally agreed that the major driving force for the irreversible adsorption
of proteins onto hydrophobic surfaces is the unfolding of the protein and sub-
sequent release of “bound” water molecules, which provides a huge increase
in the entropy of the system favoring protein adsorption. Therefore, surfaces
that retain interfacial water molecules, i.e., present an interface that “looks
like” bulk water, should have low protein adsorption. Based on this inference,
most common approaches to reducing protein adsorption onto biomaterial
surfaces involve treatments that render surfaces more hydrophilic. In fact,
simple treatments with hydrophilic biomolecules, such as albumin, casein,
dextran, and even lipid bilayers, generally reduce protein adsorption to low
levels. However, these treatments lose their nonfouling properties over time
due to displacement by other proteins and lipids and/or cell-mediated degra-
dation.
Poly(ethelyne glycol) (PEG) (-[CH
2
CH
2
O]
n
)groupshaveproventobethe
most protein-resistant functionality and remain the standard for compari-
son [37]. A strong correlation exists between PEG chain density and length
and resistance to protein adsorption, and consequently cell adhesion [38, 39].
The mechanism of resistance to protein adsorption of PEG surfaces prob-
ably involves a combination of the ability of the polymer chain to retain
interfacial water (“osmotic repulsion”) and the resistance of the polymer
coil to compression due to its tendency to remain as a random coil (“en-
tropic repulsion”) [33]. Well-packed, self-assembled monolayers (SAMs) of
EG repeats as short as three repeats display excellent nonfouling character-
istics [40, 41]. The nonfouling properties of these surfaces are dependent on
the conformation of the oligoEG chain—a helical or amorphous conform-
ation exhibits significantly higher resistance to protein adsorption compared
to an all trans conformation, probably due to stronger EG-interfacial water
interactions [42]. Other hydrophilic polymers, such as poly(2-hydroxyethyl
methacrylate), polyacrylamide, and phosphoryl choline polymers, also re-
sist protein adsorption [33]. In addition, mannitol, oligomaltose, and tau-
rine groups have emerged as promising moieties to prevent protein adsorp-
tion [43-45]. Nevertheless, more comprehensive analyses, including in vivo
studies, are required to establish the efficacy and applicability of these ap-
proaches in preventing protein adsorption and biofouling.
2.3
Substrates Modulating Adsorbed Protein Activity
Surface modifications to enhance protein adsorption and cell adhesion have
been extensively pursued to improve device performance for both in vitro
and in vivo applications. Everyday examples are tissue-culture-treated poly-
styrene and substrates for enzyme-linked immunosorbent assays (ELISA). In
these applications, the base polymer is treated to reduce hydrophobicity and
improve cell adhesion, as for tissue-culture-treated substrates, or modified to
