Synthesis, characterization and blood compatibilities of novel segmented polyurethanes containing poly (butadiene) soft segments and phosphatidylcholine analogues in the main chains and long-chain alkyl groups in the side chains

Article abstract of DOI:10.1039/a806279j

New segmented polyurethanes (SPUs) containing poly(butadiene) (PBD) soft segments and phospholipid moieties in the main chains and long-chain alkyl groups in the side chains were synthesized. The phospholipid moieties include bis [2-(2-hydroxyethyldimethylammonio)ethyl] 2-octylpropane- 1,3-diyl bis(phosphate) (OcPDP), bis [2-(2-hydroxyethyldimethylammonio)ethyl]2- oleylpropane-1,3-diyl bis (phosphate) (O1PDP) and bis[2-(2- hydroxyethyldimethylammonio)ethyl] 2-cetylpropane-1,3-diyl bis(phosphate) (CPDP). The bulk characterization of synthesized SPUs was investigated by infrared (IR) spectroscopy and gel-permeation chromatography (GPC). The mechanical properties were evaluated by dynamic viscoelasticity and tensile measurements. The existence of phospholipid analogous groups on the surface of these SPUs was revealed by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and contact angle measurements. The blood compatibilities of the new polymers were evaluated by platelet rich plasma (PRP) contact studies and viewed by scanning electron microscopy (SEM) using medical grade BioSpan and non- phospholipid polyurethane as references. These new materials have good surfaces in terms of platelet adhesion, and the morphology of adhered platelets undergoes a relatively low degree of variation.

Full text of DOI:10.1039/a806279j

J O U R N A L O F
Synthesis, characterization and blood compatibilities of novel
segmented polyurethanes containing poly(butadiene) soft segments
and phosphatidylcholine analogues in the main chains and long-chain
alkyl groups in the side chains
C H E M I S T R Y
Arata Korematsu,a Yu-Jun Li,a,b Takayuki Murakami,a Ikuko Sakurai,c Makoto Kodamad and
Tadao Nakaya*a
aDepartment of Bioapplied Chemistry, Faculty of Engineering, Osaka City University, 3-3-138
Sugimoto, Sumiyoshi-ku, Osaka 558–8585, Japan. E-mail: nakaya@bioa.eng.osaka-cu.ac.jp
bPresent Address: Procter & Gamble Far East Inc., 17 Koyo-cho Naka 1-chome, Higashinada-ku,
Kobe 658–0032, Japan
cThe Institute of Physical and Chemical Research (RIKEN), 2–1 Hirosawa, Wako, Saitama
351–0198, Japan
dBionic Design Group, National Institute for Advanced Interdisciplinary Research, 1–1-4 Higashi,
Tsukuba, Ibaraki 305–0046, Japan
Received 10th August 1998, Accepted 30th November 1998
New segmented polyurethanes (SPUs) containing poly(butadiene) (PBD) soft segments and phospholipid moieties
in the main chains and long-chain alkyl groups in the side chains were synthesized. The phospholipid moieties
include bis[2-(2-hydroxyethyldimethylammonio)ethyl] 2-octylpropane-1,3-diyl bis(phosphate) (OcPDP), bis[2-(2-
hydroxyethyldimethylammonio)ethyl] 2-oleylpropane-1,3-diyl bis(phosphate) (OlPDP) and bis[2-(2-
hydroxyethyldimethylammonio)ethyl] 2-cetylpropane-1,3-diyl bis(phosphate) (CPDP). The bulk characterization
of synthesized SPUs was investigated by infrared (IR) spectroscopy and gel-permeation chromatography (GPC).
The mechanical properties were evaluated by dynamic viscoelasticity and tensile measurements. The existence of
phospholipid analogous groups on the surface of these SPUs was revealed by attenuated total reflection Fourier
transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy ( XPS) and contact angle
measurements. The blood compatibilities of the new polymers were evaluated by platelet rich plasma (PRP) contact
studies and viewed by scanning electron microscopy (SEM) using medical grade BioSpanA and non-phospholipid
polyurethane as references. These new materials have good surfaces in terms of platelet adhesion, and the
morphology of adhered platelets undergoes a relatively low degree of variation.
separation between hard and soft segments. Moreover, these
SPUs containing hydrophobic polydiols are also interesting
for their interfacial chemistry. Due to the large difference in
surface free energy between their hard and soft segments, the
polydiol soft segments may be enriched at the air–solid
interface. However, after immersing the specimen in water,
surface reorganization may occur in response to the system’s
requirement to minimize its interfacial free energy. Moreover,
a polyurethane containing a PBD soft-segmented component
showed hardening due to the cross-linking of double bonds in
the soft segment. It was concluded that polyurethanes with
aliphatic hydrocarbon-based polydiol components are stable
against oxidative degradation.
In order to develop segmented polyurethanes with surfaces
that will not activate the blood coagulation system, a number
of surface modification approaches have been taken.12–14
Among them, an interesting and important observation is that
albumin binds via hydrophobic bonds to molecules containing
long alkyl chains, suggesting the synthesis of polymers contain-
ing alkyl chains of 16 or 18 carbon atoms15–17 as side groups.
These earlier studies suggest that improved blood compatibility
might be attained by introducing hydrocarbon groups at
the surface.
Introduction
Heart valves and other synthetic prosthetic devices in contact
with living tissue must be compatible with their biological
host. To obtain polymers with biocompatible surfaces, many
approaches have been explored. One of these approaches is to
construct segmented polyurethanes (SPUs) that exhibit bio-
stability. SPUs as biomaterials display certain favorable
mechanical properties and biocompatibilities. However, some
controversy still remains and limits their widespread appli-
cation. The SPUs most frequency used today in biomedical
applications are poly(ether urethane)s, which have good bio-
stability1–3 but which are subject to significant degradation
under certain conditions of mechanical or chemical action of
implanted devices.4–6 One of the major cause of degradation
is oxidation of the polyether chain. Oxidizing agents produced
in vivo from inflammatory cells or metal corrosion products
are associated with polyurethane degradation in implant
devices.4 It has been suggested that the major causes of
degradation are calcification, environment, stress cracking,
hydrolysis and oxidation.4,7–11
To develop polyurethane biomaterials which are more stable
in vivo, it may be desirable to prepare SPUs without ether-
containing polydiols. Takahara et al.12 have used several non-
ether polydiols such as poly(butadiene) (PBD), hydrogenated
poly(butadiene) (HPBD) and poly(dimethylsiloxane) (PDMS)
chain segments to synthesize segmented polyurethanes. They
have demonstrated that segmented polyurethanes based on
these hydrophobic polydiols showed distinct microphase
On the other hand, the possibility of utilizing polymers
containing phospholipid molecular structures on their surface
as biomaterials has been studied. Phospholipids consist of
hydrophilic and hydrophobic groups and form the lipid bi-
layers of plasma membranes.18 Phosphorylcholine, which is
an electrically neutral and zwitterionic head group that rep-
J. Mater. Chem., 1999, 9, 647–653
647

HOH2C
CH2OH
resents the bulk of the phospholipid head groups present on
the external surface of blood cells, is inert in coagulation
assays.19 In order to obtain biocompatible polymers in artificial
organs, in 1986 we successfully synthesized phospholipid-like
diols and polyurethanes.20 In recent reports on our study of
biocompatible phospholipid polymers, we described a series
of polyurethanes containing phospholipid moieties in the side
chains.21–29 Moreover, it also seemed worthwhile to investigate
the properties of polymers containing phospholipid analogues
in the main chains.30 In our previous papers,31–34 we reported
some polymers containing phosphatidylcholine analogues in
the main chains. Recently, new polyurethanes bearing phos-
phatidylcholine analogues in the main chains35–39 have been
synthesized in this laboratory.
In this study, we have synthesized several new SPUs bearing
non-ether soft segments and phospholipids in the main chains.
Furthermore, the relationships between in vitro blood con-
tacting properties and surface and bulk structure were evalu-
ated before characterizing the polymers’ stability in biological
environments. The characterization tests for bulk characteriz-
ation of the polyurethanes included IR, 1H-NMR, gel per-
meation chromatography (GPC) and elemental analysis.
Surface properties were investigated by contact angle measure-
ments, attenuated total reflection Fourier transform infrared
spectroscopy (ATR-FTIR) and X-ray photoelectron spec-
troscopy ( XPS) analyses. The blood compatibility of the
synthesized SPUs was evaluated by platelet rich plasma (PRP)
contacting experiments and the results were observed by
scanning electron microscopy (SEM). The state of platelet
adhesion and shape variation for the attached platelets were
described.
CH
R
2a–c
LiAlH4
THF
O
C
O
C
O
C
O
C
NaOEt
TEA
+
X
Et
Et
Et
Et
R
O
C
O
O
CH
O
EtOH
H2
X = Br, Cl
R
1a–c
O
P
O
P
Cl
O
O
O
C
Et N
TEA
H2C
3
+
+
2a–c
2
2
P
O
H2C
O
CH
R
O
CH2
THF
H2C
O
O
O
C
H2
H2
3a–c
H3C
N
CH2CH2OH
3a–c
H3C
∆
MeCN
CH3
N
O
P
O
P
CH3
N
HO
OH
H3C
O
O
CH
R
O
O
CH3
O
O
4 Phospholipid diol monomer
a R = CH3(CH2)7 (OcPDP)
2 7CH CH(CH2)8 (OIPDP)
c R = CH3(CH2)15 (CPDP)
b R = CH3(CH )
Scheme 1 Synthetic scheme for the preparation of the new phospholi-
pid diols.
Experimental
Materials
(1c), 2-cetylpropane-1,3-diol (2c), 1,3-bis(2-oxo-1,3,2-diox-
aphospholane-2-yloxy)-2-cetylpropane (3c) and bis[2-(2-
hydroxyethyldimethylammonio)ethyl] 2-cetylpropane-1,3-diyl
bis(phosphate) (CPDP) (4c) were prepared (Scheme 1). IR
spectra of materials were recorded on a Jasco A 202 spec-
trometer and 1H NMR spectra on a 400 MHz a FT NMR
spectrometer JNM-A 400 using tetramethylsilane (TMS) as
an internal standard.
Triethylamine
(TEA),
2-dimethylaminoethanol
(N,N-
dimethylethanolamine), 4,4∞-methylenediphenyl diisocyanate
(MDI), and butane-1,4-diol (BD) were commercially obtained
and purified by vacuum distillation. 1-Bromohexadecane,
diethyl malonate, and lithium aluminum hydride were commer-
cially obtained and used as received. Tetrahydrofuran (THF)
and diethyl ether were dried by distillation from lithium
aluminum hydride. N,N-Dimethylformamide (DMF) and
N,N-dimethylacetamide (DMAc) were distilled from calcium
hydride to ensure dryness. Methanol and ethanol were distilled
in the presence of magnesium methoxide and magnesium
ethoxide to ensure dryness. Acetone was dried by distillation
from anhydrous potassium carbonate. Poly(butadiene) diol
(PBD) with a number average molecular weight of 2840 and
60% 1,4-trans, 20% 1,4-cis, and 20% 1,2-vinyl structure
components was kindly provided by Nippon Oil and Fats
Co., Ltd.
2-Chloro-1,3,2-dioxaphospholane [bp 45.5–46.5 °C (15
mbar); lit.,40 45.5–47.0 °C (15 mbar)] was prepared in 66%
yield by the reaction of ethylene glycol with phosphorus
trichloride in dichloromethane, according to the method of
Lucas et al.,40 and oxidized to 2-chloro-2-oxo-1,3,2-dioxaphos-
pholane [bp 103.5–105.0 °C (1 mbar); lit.,41 79 °C (0.4 mbar)]
in 90% yield with oxygen, according to the procedure of
Edmundson.41 Synthesis of phospholipid diols bis[2-(2-
hydroxyethyldimethylammonio)ethyl] 2-octylpropane-1,3-diyl
bis(phosphate) (OcPDP) and bis[2-(2-hydroxyethyldimethyl-
1c: Colorless liquid; yield: 68.3%; bp 210–220 °C (8 mmHg);
d (CDCl ) 0.86–0.88 (t, 3H, CH ), 1.22–1.25 (m, 34H,
H
3
3
(CH ) , CO CH CH ), 1.87 (m, 2H, CH CH), 3.30 (t, 1H,
2 14
2
2
3
2
CH), 4.19 (m, 4H, CO CH CH ); n (neat)/cm−1 2925, 2850,
2
2
3
max
1460, 720 (CH ) and 1735 (CLO).
2
2c: White solid; yield: 79.6%; mp 45–47 °C; d (CDCl )
H
3
0.86–0.88 (t, 3H, CH ), 1.26 (s, 30H, CH ), 1.78 (m, 1H,
CH), 2.62 (s, 2H, OH), 3.63–3.83 (m, 4H, CH OH);
3
2
2
n
(KBr)/cm−1 3300, 1030 (OH), 2900, 2850, 1455 and
max
720 (CH ).
2
3c: Pale yellow viscous solid; yield: 98%; d (CDCl )
0.86–0.88 (t, 3H, CH ), 1.26 (s, 30H, CH ), 2.30 (m, 1H,
CH), 3.71–3.84 (m, 4H, POCH CH), 4.04–4.50 (m, 8H,
H
3
3
2
2
OCH CH OP); n (neat)/cm−1 2925, 2850, 1460, 720 (CH ),
2
2
max
2
1260 (PLO), and 1020 (POCH ).
2
4c: Pale yellow viscous solid; yield: 59.3%; d (CDCl )
H
3
0.86–0.88 (t, 3H, CH ), 1.26 (s, 30H, CH ), 2.89 (s, 12H,
3
2
N+CH ), 3.4–4.2 (m, 20H, OCH , N+CH ); n (neat)/cm−1
3
2
2
max
3350 (OH), 2925, 2850, 1480, 790 (CH ), 1220 (PLO) and
2
1040 (POCH ).
ammonio)ethyl]
(OlPDP) have been described in detail previously.37
2-oleylpropane-1,3-diyl
bis(phosphate)
2
Synthesis of phospholipid SPUs
Synthesis of bis[2-(2-hydroxyethyldimethylammonio)ethyl] 2-
cetylpropane-1,3-diyl bis(phosphate) (CPDP)
Phospholipid SPUs were synthesized by a three-step addition
polymerization reaction outlined in Scheme 2. The polymer
PBD1–OcPDP1 was based on 153:151 molar ratio of
PBD5MDI5OcPDP5BD and the reaction was carried out in
Using a procedure similar to that described for the preparation
of OcPDP (4a) and OlPDP (4b),37 diethyl 2-cetylmalonate
648
J. Mater. Chem., 1999, 9, 647–653

HC CH2
CH2
Preparation of cast films
CH2CH CH2CH
trans-1,4 60%
OH
HO
CH
y
x
After briefly drying under vacuum to remove residual
methanol, the resulting polymers were dissolved in a casting
solvent using an ultrasonic generator, and then cast onto glass
plates to create films for bulk property testing or surface
property experiments. In the casting procedure, the cast films
were first dried in an oven at 70 °C for at least 24 h to remove
most of the solvents. The final drying stage involved drying
the sheet in a vacuum oven at 70 °C for at least 24 h to remove
residual solvents.
n
Mn = 2840
cis-1,4
20%
Polybutadiene
(PBD)
vinyl-1,4 20%
+
CH2
3
OCN
NCO
MDI
N2 , DMAc/THF
70–75 ˚C, 1 h
Measurements
+
Prepolymer
MDI (unreacted)
IR spectra were recorded on a Jasco A 202 spectrometer. GPC
measurements were performed on a HLC802UR GPC instru-
ment with G4000H8+G2000H8 columns; the samples were
dissolved in mixed solvent of THF and DMAc (volume ratio
151) and polystyrene was used as standard. The surface of the
cast films was analyzed by XPS using a Shimadzu ESCA 750
spectrometer using Mg-Ka radiation. The cast films, after
peeling from the glass, were mounted on the specimen holder.
The typical operating conditions included maintaining the X-
ray gun at 8 kV and 30 mA and reducing the pressure in the
sample chamber to about 3×10−5 Pa. The take-off angle of
the photoelectrons was 60°. The repeat times were once for
carbon and oxygen, and five times for nitrogen and phos-
phorus, respectively. In addition to taking survey scans
(0–1000 eV) with a view to determining the elemental composi-
tion of the various surfaces, elemental compositions were also
N2 , DMAc–THF
90–100 ˚C, 3 h
Phospholipid Diol
(OcPDP, OlPDP, CPDP)
HO (CH2)4 OH
N2 , DMAc–THF
100–110 ˚C, 1 h
BD
{(MDI-Phospholipid Diol); (MDI-BD)}]m
[MDI-PBD
SPUs
Scheme 2 Three-step synthesis of the phospholipid SPUs.
a 151 mixture of DMAc–THF without catalyst. In the first
step, 1.06 g (4.23 mmol) of MDI dissolved in 10 cm3 of mixed
solvent was added to the stirred solution of 4.0 g (1.41 mmol)
of PBD and 10 cm3 of the same mixed solvent under a dry
nitrogen atmosphere. After stirring for 1 h at 70–75 °C, the
solution was cooled to room temperature. In the second step,
0.81 g (1.41 mmol) of OcPDP, previously dissolved in 15 cm3
of the mixed solvent, was slowly added to the reaction solution
over 1 h. Stirring was continued at 90–100 °C for 3 h. For the
last step, 0.13 g (1.41 mmol) of BD, previously dissolved in
15 cm3 of the same mixed solvent, was slowly added into the
reaction solution over 20 min. The stirring was continued at
100–110 °C for 1 h. The resulting phospholipid polymer was
precipitated in methanol. The polymer was then washed with
methanol and the washing procedure was performed three
additional times with methanol. The polymer was dried under
vacuum. The polymer PBD1–OcPDP1 was obtained in 96.5%
yield as a pale yellow elastomer. Using a procedure similar to
that described for the preparation of PBD1–OcPDP1, other
new polyurethanes, PBD1–OlPDP1 and PBD1–CPDP1 were
also synthesized. The polymer PBD1–OlPDP1 was obtained
in 81.1% yield and PBD1–CPDP1 in 87.0% yield and both
polymers were pale yellow elastomers.
determined on the basis of the peak areas from the C , N ,
1s 1s
O
and P orbitals. Peak areas were calculated using standard
1s
2p
Shimadzu ESPAC 100 software. The binding energy was
referenced by setting the C hydrocarbon peak to 285 eV.
1s
Contact angle measurements: the values quoted are the average
of 10 measurements of each sample taken for the immediate
contact of the water droplet, on the air exposed side, using a
FACE contact angle meter. The temperature dependence of
the dynamic viscoelasticity of the sample was obtained using
a microprocessor-controlled Rheovibron DDV-01FP under a
nitrogen purge. The sample (205 mm thick, 2 mm wide, 30 mm
long) was cooled to −150 °C, and data were subsequently
taken at a test frequency of 11 Hz and a heating rate of
3 °C min−1. The stress–strain properties were measured using
an Instron type tensile tester (Tenshiron Model UCT-30T)
with a crosshead speed of 12 mm min−1 at room temperature.
ATR-FTIR was performed on the surfaces of the cast films.
The spectra were collected at 4 cm−1 resolution using a Jasco
Micro FT/IR-200 microsampling spectrometer over 50 scans.
The sampling area was 25 mm2, coupled with an ATR accessory
and 45° KRS-5 crystal. The procedure of blood compatibility
evaluation for blood platelet adhesion and shape variation
was the same as that described previously.23,25–29,38,39,43
Briefly, the cast films were washed with saline and incubated
at 37 °C for 1 h with freshly prepared PRP which was obtained
from the centrifugation of the blood of rabbits. Samples were
rinsed with saline and treated with 2.5% glutaraldehyde in
To investigate the effect of the phospholipid component, a
reference SPU based on PBD and extended only with BD was
also synthesized, according to a conventional two-step solution
polymerization procedure under nitrogen atmosphere.42 This
polymer was based on 15352 molar ratio of PBD5MDI5BD
and the reaction was carried out in a 151 mixture of
THF–DMAc without catalyst (Table 1).
Table 1 Bulk property characterization of phospholipid SPUs and the reference SPU
IR spectral data/cm−1
Stoichiometrya
PBD5MDI5XPDP5BD
Hard
segment (%)
Yield
(%)
SPUs
NH
CH
NHCOO
PLO
POCH
M b
2
2
w
PBD1–OcPDP1
PBD1–O1PDP1
PBD1–CPDP1
Reference SPU
1535151
1535151
1535151
1535052
33.3
35.4
35.0
24.7
96.5
81.1
87.0
98.1
3300
3300
3300
3300
2925, 2850, 1460
2925, 2850, 1460
2925, 2850, 1460
2925, 2850, 1460
1710
1710
1710
1710
1220
1220
1220
—
1060
1060
1060
—
55000
53000
70000
75000
aXPDP includes OcPDP (for PBD1–OcPDP1), O1PDP (for PBD1–O1PDP1), CPDP (for PBD1–CPDP1). bDetermined by GPC using
polystyrene as standard.
J. Mater. Chem., 1999, 9, 647–653
649

0.1  cacodylate buffer at refrigerated temperatures overnight.
The samples were rinsed with 0.1  cacodylate buffer three
times and dehydrated by systematic immersion in a series of
ethanol–water solutions (60, 70, 80, 90, 95 and 100 vol%).
Following critical point drying with carbon dioxide, the
samples were coated with gold for analysis by SEM using a
Shimidzu EPM-810.
Results and discussion
Synthesis of CPDP
The synthetic procedure is outlined in Scheme 1. According to
the method of Hsu and Percec,44 compound 1c was obtained
by the reaction of 1-bromooctadecane with diethyl malonate
in ethanol in the presence of sodium ethoxide. Compound 2c
was obtained by reduction of 1c in THF in the presence of
LiAlH . The characterization of 1c and 2c was based on their
4
IR and 1H NMR spectral data and elemental analyses. The
Fig. 1 Temperature dependence of the (#) storage modulus (E∞), (+)
loss modulus (E◊) and (×) loss tangent (tan d) for the phospholipid
segmented polyurethane PBD1–CPDP1 at 11 Hz.
bifunctional intermediate 3c was obtained by the reaction of
2c with 2-chloro-2-oxo-1,3,2-dioxaphospholane in THF in the
presence of TEA. It was characterized by IR and 1H NMR
spectral data. According to the method of Thuong and
Chabrier,45 the ring-opening reaction of 3c was performed
with 2-dimethylaminoethanol in acetonitrile at 70 °C for 20 h
to afford new diol 4c as a pale yellow viscous solid in good
yield. The characterization of the new diol 4c was based on
its IR and 1H NMR spectral data and elemental analysis. This
diol was very hygroscopic and soluble in DMF at 70 °C, but
almost insoluble in acetone and diethyl ether at room
temperature.
Table 2 Mechanical properties of PBD1–CPDP1
Sheet thickness/ Ultimate modulus/ 100% Modulus/ Elongation
mm
MPa
MPa
at break (%)
205
5.46
3.26
233
phospholipid SPUs are, relatively, weaker than medical grade
segmented polyurethane BioSpanA.46
Bulk property characterization
Surface property characterization
Bulk property characterization data are summarized in Table 1.
The stoichiometry of the reaction was 1535151 for
PBD5MDI5XPDP5BD. XPDP includes OcPDP (for
PBD1–OcPDP1), OlPDP (for PBD1–OlPDP1) and CPDP
(for PBD1–CPDP1). The designed hard segment was in the
range 33.3–35.4%. The IR spectral analyses of the polymers
were taken on cast films. All phospholipid polymers are related
with the inclusion of PBD, MDI and phospholipid moieties.
This is clear from the complete IR spectrum of each material,
which shows absorption due to an NH band at 3300 cm−1,
an NHCO band at 1710 cm−1, CH bands at 2925, 2850 and
The surface properties of the cast films of the resulting
polymers were investigated by ATR-FTIR, XPS and contact
angle measurements. In previous papers,25,26,47 the surface
properties and blood compatibilities of polymers were found
to be different for the surfaces exposed either to air or to the
mold substrate during the solvent casting process. In this
study, the air-exposed surface of the phospholipid polymers
was the blood contacting surface. Therefore, all surface and
blood compatible properties were related to the air-exposed
surface.
Fig. 2 shows the ATR-FTIR spectra of PBD1–CPDP1 and
the reference SPU. The spectra of the polymers give evidence
2
2
1460 cm−1, an aromatic linkage at 1600 cm−1, a PLO at
1220 cm−1 and a POCH at 1060 cm−1. The molecular weights
of unsaturated CLC double bonds, PO −, NH, CLO bonds,
2
4
of the polymers were characterized by GPC based on a
nonbonded and bonded urethane, and unsaturated aromatic
polystyrene standard. From the relationship between retention
time and molecular weights derived for narrowly distributed
standard polystyrene, the weight average molecular weights
bonds. The analysis of PBD composition has been discussed
in detail in our previous articles.26,38 The peaks at 3075 cm−1
due to CHLCH unsaturated vinyl, at 964 due to trans-1,4
addition of CHLCH, at 680 owing to cis-1,4 addition of
(M ) of PBD1–OcPDP1, PBD1–OlPDP1, PBD1–CPDP1 and
w
the reference SPU were 55000, 53000, 70000 and 75000. These
CHLCH and at 993 and 910 due to 1,2 addition of CHLCH
2
molecular weights are sufficient for most biomedical
applications.
have been observed. The NH absorption band was found at
3311 cm−1. The peak at 1708 cm−1 has been assigned to
carbonyl groups that are hydrogen bonded (presumably to
the urethane hydrogens) and the peak at 1730 cm−1 has been
assigned to carbonyl groups that are not hydrogen-bonded.
Moreover, a relatively weak band at 1641 cm−1 due to amide
I and a peak at 1595 cm−1 due to aromatic stretching were
clearly observed. Compared to the reference SPU without
phospholipid analogous groups, PBD1–CPDP1 displays
additional stretching at 1240 and 1050 cm−1 due to PLO and
The typical results of a dynamic viscoelasticity experiment
for the PBD1–CPDP1 film sample are displayed in Fig. 1. For
PBD1–CPDP1, the storage modulus (E∞) slowly decreased
from 4.51×10 MPa at −150 °C to 2.59×103 MPa at −80 °C,
and then rapidly decreased by about two orders of magnitude.
The material was followed into the elastomer region, giving
47 MPa near −50 °C. The peak of tan d was observed at
−64 °C, together with the peak of loss modulus (E◊) at -78 °C.
At 36.1 °C, 17.6 MPa, 1.21 MPa, and 0.0691 for E∞, E◊ and
tan d were observed.
The tensile property data for the PBD1–CPDP1 film sample
are summarized in Table 2. When the film sheet thickness was
205 mm, this elastomer had 3.26 MPa 100% modulus, and
5.46 MPa ultimate strength. Moreover, this elastomer had
good mechanical strength with an elongation at break of
233%. However, the mechanical properties of these synthesized
PO–CH bonds.
2
Fig. 3 shows typical C , O , N and P spectra for
1s
1s
1s
2p
PBD1–CPDP1 acquired at an 60° take-off angles. These
spectra suggest a surface dominated by the PBD soft segment
with urethane. The urethane (NH–COO) peak, when com-
pared to the hydrocarbon (C–C–C) peak at 285.15 eV, is too
small to allow accurate peak resolution. A Gaussian peak at
532.75 eV was used to fit the PBD1–CPDP1 O peak. The
1s
650
J. Mater. Chem., 1999, 9, 647–653

Fig. 2 ATR-FTIR spectra of PBD1–CPDP1 (solid line) and the reference SPU (dashed line).
and a small amount of P on the surface of the polymers.
2p
The ratio of elemental bulk composition of phosphorus is in
the range of 1.56–1.61 and the ratio of elemental surface
composition is in the range of 0.27–1.09. The ratios of the
peak areas of oxygen, nitrogen and phosphorus to that of
carbon (O /C , N /C , and P /C ) were calculated and are
1s 1s 1s 1s
2p 1s
also summarized in Table 3. The P /C values of the phospho-
2p 1s
lipid SPUs were in the range of 0.0032–0.0144. The P data
2p
suggest that phosphatidylcholine analogous groups are present
on the surface of these synthesized phospholipid SPUs.
To investigate the hydrophilicity–hydrophobicity of the
surfaces of the polymers, water contact angle measurements
were carried out (Table 3). As expected, the relatively large
contact angles indicated that these polymers had hydrophobic
surfaces. PBD1–OcPDP1, PBD1–OlPDP1 and PBD1–CPDP1
exhibited contact angles of 92.1 3, 90.1 3 and 94.7 5°.
These results agree with those of the XPS experiments, with
samples having high carbon contents on the surface showing
relatively strong hydrophobicity.
Fig. 3 XPS spectra of the cast film surface of PBD1–CPDP1.
high-energy and low-energy tailings on the O peak reflect a
combination of hole state lifetime broadening contributions
Blood compatibility evaluation
1s
from the urethane oxygens (N–COO and N–COO) and phos-
The synthesized phospholipid SPUs were assessed as
biomaterials mainly by the degree and nature of blood platelet
adhesion resulting from exposure to rabbit PRP for 60 min.
The specimens incubated in PRP were viewed by SEM. This
experiment was repeated twice and ten SEM photographs in
various places were taken for each sample. Then, the mean
values of the number of attached platelets and the platelet
density were evaluated from these photographs. Typical SEM
photographs of medical grade BioSpanA, PBD1–OcPDP1,
phorus oxygens (PO −). The high-energy and low-energy
4
tailings on the N peak also reflect a combination of hole
1s
state lifetime broadening contributions from the urethane
nitrogen (N–COO) and phospholipid ammonium nitrogen
[N+(CH ) ]. The nitrogen binding energy was 400.50 eV. A
3 2
Gaussian peak at 134.30 eV was used to fit P peak (PO −).
2p
4
Table 3 lists XPS elemental surface composition of the
synthesized polymers. All samples show a large amount of C
1s
Table 3 XPS elemental surface composition (%) and water contact angle (°) of the phospholipid SPUa
SPU
C
O
N
P
O /C
1s 1s
N /C
1s 1s
P
/C
[h]
1s
1s
1s
2p
2p 1s
(air)
PBD1–OcPDP1
PBD1–O1PDP1
PBD1–CPDP1
84.47
(87.17)
81.86
(87.56)
76.12
13.93
(8.31)
16.66
(8.06)
21.28
(8.11)
1.33
(2.91)
1.13
(2.82)
1.50
0.27
(1.61)
0.35
(1.56)
1.09
0.1649
0.2035
0.2796
0.0157
0.0138
0.0197
0.0032
0.0043
0.0144
92.1 ( 3.0)
90.1 ( 3.0)
94.7 ( 5.5)
(87.49)
(2.84)
(1.57)
aValues in parentheses are expected theoretical elemental bulk compositions (%).
J. Mater. Chem., 1999, 9, 647–653
651

Fig. 4 SEM photographs of the surface of phospholipid SPUs, the reference SPU and medical grade BioSpanA films after 60 min of rabbit PRP
exposure: (a) PBD1–OcPDP1, (b) PBD1–OlPDP1, (c) PBD1–CPDP1 (d) the reference SPU film cast from mixed THF and DMAc (volume
ratio 151) solution and (e) medical grade BioSpanA film cast from DMAc solution (actual magnification: ×2000).
PBD1–OlPDP1, PBD1–CPDP1 and the reference SPU are
shown in Fig. 4.
The apparent ‘degree of shape variation of platelets’ was in
the order:
The surface of PBD1–CPDP1 did not show any substantial
platelet attachment. Moreover, the shape variation of the
adhered platelets, i.e. tail-forming or spreading, was very
limited. On the other hand, the surfaces of PBD1–OcPDP1
and PBD1–OlPDP1 exhibited some attached platelets with
some degree of shape variation. In contrast with phospholipid
SPUs, medical grade segmented polyurethane BioSpanA and
the reference SPU not only exhibited substantial platelet
adherence, they also showed some degree of shape variation
for the adhered platelets. Blood platelets were detected on all
cast films exposed to PRP for 60 min, and the qualitative
results of the PRP trials are summarized as follows:
BioSpanA and reference SPU>PBD1–OlPDP1>PBD1–
OcPDP1>PBD1–CPDP1.
On the basis of the SEM observations, the number of
adhered platelets in an area of 10×10 mm was 0.69, 6.06, 7.48,
8.77 and 10.15 for PBD1–CPDP1, PBD1–OlPDP1,
PBD1–OcPDP1, the reference SPU and BioSpanA, respect-
ively. Although the shape variation of the adhered platelets
may affect the accuracy of the estimated number of adhered
platelets, it was apparent that the trend of blood compatibilities
of the phospholipid SPUs are better than that of the reference
SPU and BioSpanA.
The apparent ‘number of attached platelets’ was in the order:
As is seen from these results, the synthesized phospholipid
polyurethanes, especially PBD1–CPDP1, have good surface
properties in terms of platelet adhesion and the fact that the
BioSpanA and reference SPU>PBD1–OcPDP1 and
PBD1–OlPDP1>PBD1–CPDP1.
652
J. Mater. Chem., 1999, 9, 647–653

21 M. Yamada, Y.-J. Li and T. Nakaya, J. Macromol. Sci. Pure Appl.
Chem., 1995, A32, 1235.
22 Y.-J. Li, Y. Shibata and T. Nakaya, Macromol. Chem., Rapid
Commun., 1995, 16, 253.
23 Y.-J. Li, K. H. Matthews, M. Kodama and T. Nakaya, Macromol.
Chem. Phys., 1995, 196, 3143.
morphology of platelets undergoes a relatively low degree of
variation. The development of such blood-compatible phos-
pholipid polyurethanes with good mechanical properties is
ongoing in our group.
24 Y.-J. Li, R. Bahulekar, T.-M. Chen, Y.-F. Wang, M. Kodama and
T. Nakaya, Macromol. Chem. Phys., 1996, 197, 2827.
25 Y.-J. Li, T. Yokawa, K. H. Matthews, T.-M. Chen, Y.-F. Wang,
M. Kodama and T. Nakaya, Biomaterials, 1996, 17, 2179.
26 Y.-J. Li, K. H. Matthews, T.-M. Chen, Y.-F. Wang, M. Kodama
and T. Nakaya, Chem. Mater., 1996, 8, 1441.
27 Y.-J. Li, R. Bahulekar, Y.-F. Wang, T.-M. Chen, M. Kitamura,
M. Kodama and T. Nakaya, J. Biomater. Sci. Polym. Ed., 1996,
7, 893.
28 Y.-J. Li, K. H. Matthews, Y.-F. Wang, T.-M. Chen, M. Kodama
and T. Nakaya, J. Appl. Polym. Sci., 1996, 62, 687.
29 Y.-J. Li, T. Tomita, K. Tanda and T. Nakaya, Chem. Mater.,
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30 T. Nakaya and S. Nakai, Kagaku (in Japanese), 1987, 42, 725.
31 T. Umeda, T. Nakaya and M. Imoto, Makromol. Chem., Rapid
Commun., 1985, 6, 285.
32 K. Sugiyama and T. Nakaya, Makromol. Chem., Rapid Commun.,
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33 T. Nakaya, M. Yasuzawa and M. Imoto, Macromolecules, 1989,
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34 M. Yamada, Y.-J. Li and T. Nakaya, J. Macromol. Sci. Pure Appl.
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35 M. Yamada, Y.-J. Li and T. Nakaya, Macromol. Chem., Rapid
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36 Y.-J. Li, N. Nakamura, T. M. Chen, Y.-F. Wang, M. Kitamura
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37 A. Korematsu, Y.-J. Li and T. Nakaya, Polym. Bull., 1997, 38,
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38 Y.-J. Li, N. Nakamura, Y.-F. Wang, M. Kodama and T. Nakaya,
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40 H. J. Lucas, F. W. Mitchell and C. N. Scully, J. Am. Chem. Soc.,
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Acknowledgements
The authors are grateful to Professor T. Endo, Tokyo Institute
of Technology, Yokohama (Japan), for helpful suggestions
concerning the preparation of compounds 2a, 2b and 2c.
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