Biomedical Engineering Reference
In-Depth Information
c
a
b
Cast and UV irradiation
CH
2
CH
CH
2
CH
n
m
C=O
N
UV
n : m = 92 : 8
N
3
CH
3
CH
3
Phenyl azide
Tissue culture dish
d
N
3
CONH
CH
2
CH
2
O
NHCO
N
3
Copolymer
n
Washing
CH
2
CH
CH
2
CH
n
m
n : m = 93 : 7
Tissue culture dish
100 µm
N
3
FIGURE 2.24
Micropatterning.of.photoreactive.copolymers..(From.Takehisa.Matsuda.and.Takashi.
Sugawara,.“Control.of.cell.adhesion,.migration,.and.orientation.on.photochemically.microprocessed.
surfaces,”.
J. Biomed. Mater. Res.
32,. 165,. 1996.. Reprinted. with. permission.of. John. Wiley. and.
Sons..Figure.contributed.by.Takehisa.Matsuda.)
groups on UV irradiation. he hydrophilicity of the unirradiated copolymer could be designed
by choosing diferent monomers. When a thin ilm of copolymer was cast on a polymeric sur-
face such as polystyrene or polyvinyl alcohol, and exposed to UV irradiation through a chrome
mask, only the exposed parts of the copolymer ilm bonded to the underlying surface; hence,
creating a polymer-on-polymer pattern with high hydrophilicity contrast. hey were able to
create micropatterns of photoreactive (hydrophobic) styrene copolymer cast onto (hydrophilic)
polyvinyl alcohol and micropatterns of photoreactive (hydrophilic) dimethyl acrylamide copo-
lymer cast onto (hydrophobic) polystyrene. Endothelial cells were observed to attach with high
selectivity only on the hydrophobic parts of the substrate. Unfortunately, no details were given
on possible protein exposures and the selective attachment was interpreted only as a result of
diferential surface wettability—it was claimed that the photosensitized copolymers prevented
the adsorption of ECM protein onto the irradiated, highly hydrophilic areas. With this system,
nevertheless, selective attachment and growth of neuroblastoma cells for more than 1 month
was demonstrated, and endothelial cells were observed to migrate only along adhesive tracks.
Because little experimental details and no protein physisorption data were provided, the ques-
tion remains whether cell attachment was indeed mediated by physisorption of proteins. he
same strategy was later extended to other copolymers.
Of all photosensitive polymers, the most widely available are the photoresists used in
microelectronics processing, and their photochemistry is extremely well characterized. So
why not give it a try? In the early 1990s, André Kléber and colleagues at the University of
Bern (Switzerland) studied the behavior of neonatal rat heart cells cultured on photoresist
patterns (on glass). hey found that the photoresist resisted the attachment of cells and the
shape and orientation of the individual myocytes were a function of photoresist channel
width. Surprisingly, it did not show signs of cytotoxicity as assessed by morphology and elec-
trophysiology measurements for up to 17 days of culture. he cytotoxicity and attachment
selectivity of photoresist for other cell types remains to be assessed (or, more likely, many
laboratories keep testing them and do not report their negative results). he Yoshikawa group
at the Osaka National Research Institute published a study in which a range of photoresists
and surface modiication schemes routinely used in microelectronics was tested for neuron
and glial cells seeded in serum-containing medium. he cells attached preferentially onto the
0.6-μm-thick photoresist patterns on a glass background only for certain photoresists; the
