Biomedical Engineering Reference
In-Depth Information
was observed for both PEI/heparin and CH/hyaluronic acid (CH/HA) multilayer assembly. The in
vitro hemocompatibility of CH/HA-coated NiTi surfaces and PEI/heparin-modifi ed 316L stainless
steel surfaces were tested through a standard platelet adhesion method [57,58]. Both coatings have
shown signifi cant reduction in platelet adhesion compared with unmodifi ed surfaces, indicating
better hemocompatibility and a lesser chance of thrombus formation on the implants. Through
radiolabeling, quantitative platelet adhesion was measured as 619.7
103 platelets/cm
2
on
±
258.0
×
103 platelets/cm
2
for bare NiTi (
p
HA(CH/HA)
4
-coated metallic versus 1005.9
0.05)
[58]. Platelet adhesion is known to be initiated by adsorption of plasma proteins such as fi brinogen.
The antifouling properties of HA was believed to be attributable to the hydration layer surrounding
HA molecules on the surface [85].
Further application of LbL self-assembly thin fi lm deposition can be extended to tissue repair
with advantages including broad selection of materials, precise control over structures at a molecular
level, and friendly environment during process. For example, the Tabrizian group recently demon-
strated that it was possible to build a nanoscale self-assembled multilayer on damaged arteries
through alternating depositions of two polysaccharides, HA and CH [86]. Insulation of the vascular
wall by using polyelectrolyte coatings provides a shield against blood components, especially plate-
lets, resulting in a much lower chance of thrombus formation.
±
97.7
×
<
10.2.4 D
RUG
I
NCORPORATION
IN
P
OLYELECTROLYTE
F
ILMS
Multilayered polyelectrolyte fi lm may provide a passive protection at a certain degree on implant
surfaces. Incorporation of active agents in the fi lm with a controlled release fashion will extend the
function of biointerface. So far, two approaches have been explored: (1) the multilayer coatings were
used as a reservoir for drug storage and delivery [58] and (2) prodrug polyion-drug (HA-paclitaxel)
conjugation was assembled into polyelectrolyte fi lms [87].
Sodium nitroprusside (SNP), an anionic nitrous oxide donor used clinically to reduce blood pres-
sure and treat restenosis, has been incorporated into CH/HA polyelectrolyte multilayers following a
method used to introduce ionic dyes and proteins within polyelectrolyte multilayers [88]. Briefl y, it was
doped within the coating during the CH deposition step, as the cationic polysaccharide is able to form
a complex with SNP by electrostatic interactions [58]. LbL fi lm growth was not interrupted after intro-
duction of SNP. During
in vitro
hemocompatibility test, incorporation of SNP within the multilayered
coating further decreased platelet adhesion by 40% compared with CH/HA-paired multilayers.
The second strategy, “prodrug approach” was used to introduce paclitaxel (PTX) into polyelec-
trolyte multilayers [87]. Instead of using passive adsorption during LbL self-assembly, the drug PTX
was fi rst linked to a HA via a hydrolyzable bond (succinate ester linkage) and later assembled into
the fi lm. This methodology has advantages in solubilization of hydrophobic drugs and tunability
of the drug pharmacokinetics [89]. A 2
-hemisuccinate derivative of PTX was prepared fi rst, as
previously reported [90], activated to the corresponding
N
-hydroxysuccinimide (NHS) ester, and
linked to an amine-modifi ed HA. The level of PTX incorporation onto HA was intentionally kept
low to preserve the water solubility of the prodrug. Self-assembly of CH and HA-Pac was success-
ful, as higher QCM frequency shifts for CH/HA-Paclitaxel multilayers were noticed than CH/HA
coating. It was suggested that the presence of the hydrophobic PTX moieties did not prohibit the
construction of multilayers, although the growth mechanism may be affected [87]. The total amount
of PTX released was 1.8 µg/cm
2
from HA-Pac(CH/HA-Pac)
9
multilayers with 50% and 90% drug
release corresponding to 3 and 10 h, respectively. For potential
in vivo
applications, a longer drug
release time is preferred (e.g., a few days to a few months).
′
10.2.5 M
ICROPATTERNING
OF
S
ELF
-A
SSEMBLED
S
TRUCTURES
Micropatterning of biomolecules on a substrate has important applications, including immuno-
assays, genetic disease screening, chemical and biomedical sensors, drug screening, and tissue
engineering. Whitesides et al. were among the fi rst to pattern self-assembled monolayers (SAMs)
