Synthesis and characterization of functionalizable and photopatternable poly(ε-caprolactone-co-RS-β-malic acid)

Article abstract of DOI:10.1021/ma050545j

To create a functionalizable and photopatternable biodegradable polyester, 2-hydroylethyl methacrylate (HEMA) grafted poly(ε-caprolactone-co-RS- β-malic acid) (PCLMAc) was synthesized. The ring-opening random copolymerization of ε-caprolactone (CL) and RS

Full text of DOI:10.1021/ma050545j

Macromolecules 2005, 38, 8227-8234
8227
Synthesis and Characterization of Functionalizable and
Photopatternable Poly(ꢀ-caprolactone-co-RS-â-malic acid)
Bin He and Mary B. Chan-Park*
The Biological and Chemical Processing Laboratory, School of Mechanical and Production
Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore
Received March 14, 2005; Revised Manuscript Received July 20, 2005
ABSTRACT: To create a functionalizable and photopatternable biodegradable polyester, 2-hydroylethyl
methacrylate (HEMA) grafted poly(ꢀ-caprolactone-co-RS-â-malic acid) (PCLMAc) was synthesized. The
ring-opening random copolymerization of ꢀ-caprolactone (CL) and RS-â-benzyl malolactonate (MA) using
1
stannous octoate catalyst was systemically studied. The polymers were characterized by H NMR, FTIR,
GPC, and DSC. The optimum copolymerization temperature was found to be 130 °C. The proportion of
MA in the derived copolymers was lower than that in the feeding dose, a consequence of its lower reactivity.
The molecular weight of the copolymers decreased with increasing MA content. During hydrogenolysis,
the protective benzyl groups were completely replaced by carboxyl groups resulting in hydrogen bonding
in the deprotected copolymers, but some degradation occurred. PCL segments in the copolymers
crystallized when the MA content was lower than 16.2 mol %, and the deprotected copolymer had higher
crystallinity compared to that of the corresponding protected copolymer. The glass transition temperature
(T
g
) of the deprotected copolymer increased greatly due to the formation of hydrogen bonds. HEMA was
easily grafted on the functionalized biodegradable copolymer. The liquid HEMA grafted copolymer was
shown to be suitable for UV microembossing.
Introduction
tionalization of biodegradable polyesters with poly(â-
malic acid) has been previously reported,27 but these are
solids at room temperature. Among the synthetic bio-
degradable polyesters, only poly(ꢀ-caprolactone) (PCL)
has low Tg and Tm.17 Since poly(malic acid) has pendant
functional groups and PCL has low Tg and Tm, the
random copolymer of ꢀ-caprolactone and â-malic acid
would combine the desired thermal properties of PCL
and functional pendant groups of poly(â-malic acid)
Synthetic biodegradable polyesters such as poly-
(
(
glycolic acid) (PGA), poly(lactic acid) (PLA), and poly-
ꢀ-caprolactone) (PCL) have been widely used as bio-
medical materials due to their excellent mechanical
properties, good biocompatibility, and low toxicity.1
However, these common aliphatic polyesters lack func-
tionality necessary for some processing techniques or
biomolecules immobilization, limiting their use in bio-
medical applications. Micropatterned tissue engineering
scaffolds have been shown to be useful for the vascula-
ture or guided nerve regeneration.5,6 Many micropat-
terning techniques abound, and these include photo-
lithography, soft lithography, and embossing. UV
-4
(PMAc). The random copolymer of ꢀ-caprolactone and
malic acid, which has not been reported thus far, could
be tailored by adjusting the proportions of the two
monomers in the coordination ring-opening copolymer-
ization. The modification of functionalized biodegradable
polymer would promote biospecific cell recognition and/
or signaling necessary for regeneration of a multicellular
organ.1
microembossing, a liquid micromolding technique, has
been shown to be versatile and convenient.7
-9
For
8-20
example, the UV microembossed films can be folded into
tubular scaffolds for tissue engineering of small diam-
This paper reports the random copolymerization and
subsequent hydrogenolysis of ꢀ-caprolactone and RS-â-
benzyl malolactonate to produce poly(ꢀ-caprolactone-co-
RS-â-malic acid) (PCLMAc)sa new liquid biodegradable
polyester with functional pendant groups. Further, the
UV microembossing of 2-hydroxyethyl methacrylate
9
eter blood vessels. However, hitherto, the liquid poly-
mers used in UV microembossing are nonbiodegradable,
making the scaffolds unsuitable for tissue engineering
7
-9
scaffold.
Photopatternable and functionalizable bio-
degradable polymers are limited. To apply the UV
microembossing technique to functional tissue engineer-
ing scaffold fabrication, new materials must be designed
to (1) be biodegradable, (2) be a low surface tension
liquid to fill and closely replicate the microcavities of
the mold, and (3) have functional groups to provide
cross-linking sites as well as biomolecules grafting.
(
HEMA) grafted PCLMAc is also demonstrated. In the
copolymerization, the relationship between the reaction
parameters (catalyst concentration, monomer ratio, and
copolymerization temperature) and the copolymer prop-
erties (yield, molecular weight, polydispersity, and
composition) was studied. The copolymers are charac-
terized with nuclear magnetic resonance (NMR), Fourier
transform infrared spectroscopy (FTIR), gel permeation
chromatography (GPC), and differential scanning cal-
orimetry (DSC). The UV microembossing of HEMA-g-
PCLMAc is characterized by scanning electron micros-
copy (SEM).
Poly(â-malic acid), a synthetic biodegradable polyester
with functional pendant carboxylic groups, is of great
interest for biomedical applications.1
0-15
The degrada-
tion product of poly(malic acid) is malic acid, which is
an intermediate compound in the Krebs’ cycle necessary
to generate cellular energy for tissue fuel. The func-
Experimental Section
*
To whom correspondence should be addressed: e-mail
Materials. All chemicals were purchased from Aldrich. RS-
bromosuccinic acid was recrystallized in acetonitrile twice;
mbechan@ntu.edu.sg; Tel (65) 6790 6064; Fax (65) 6792 4062.
1
0.1021/ma050545j CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/01/2005

8
228 He and Chan-Park
Table 1. Copolymerization of E-Caprolactone and RS-â-Benzyl Malolactonate
MA content
mol wt of copolymerb
Macromolecules, Vol. 38, No. 20, 2005
entries
temp (°C)
Sn(Oct)2
feed
polymera
Mn
Mw
Mw/Mn
yield (%)
A
B
C
D
E
F
G
H
I
110
130
150
170
130
130
130
130
130
130
130
1/1000
1/1000
1/1000
1/1000
1/1000
1/1000
1/1000
1/1000
1/1000
1/500
12.2
12.2
12.2
12.2
0
27.0
45.3
68.9
5.9
6.8
4 700
20 500
13 800
12 100
95 700
13 400
10 300
8 100
9 700
29 200
21 300
17 400
198 000
19 800
14 300
10 500
5 700
2.06
1.42
1.54
1.44
2.07
1.48
1.39
1.30
1.97
1.48
1.44
73
88
85
80
95
87
82
82
80
87
86
7.0
6.3
0
16.2
35.0
64.7
100
6.9
100
12.2
12.2
2 900
J
19 300
20 600
28 600
29 700
K
1/2000
6.5
a
1
b
Calculated from H NMR measurement. Determined by GPC measurement.
Table 2. Variation of Compositions and Molecular Weight
of Poly(E-caprolactone-co-RS-malic acid) after
Hydrogenolysis
benzyl alcohol was used after distillation. ꢀ-caprolactone (CL)
was dried with sodium and distilled before use. Stannous
octoate, trifluoroacetic acid anhydride (TFAA), sodium hydro-
gen carbonate, sodium hydroxide, magnesium sulfate, pal-
ladium on charcoal (Pd/C), and activated charcoal were used
as received. N,N′-Dicyclohexylcarbodiimide (DCC) and 2-hy-
droylethyl methacrylate (HEMA) purchased were used without
further purification. The photoinitiator 2,2-dimethoxy-2-phen-
ylacetophenone was supplied as Irgacure 651 by Ciba Chemi-
cals. Tetrahydrofuran (THF) and diethyl ether were dried with
sodium and distilled. Dichloromethane, acetonitrile, chloro-
form, and petroleum ether were dried with calcium hydride
mol wt of
copolymer
b
malic acid in
entriesc PCLMAc (%)
a
Mn
Mw
Mw/Mn yield (%)
d-E
d-B
d-F
d-G
d-H
d-I
0
55 300 104 500
1.89
1.60
1.58
1.61
1.58
1.20
98
85
86
84
83
80
6.5
11 600
8 500
4 400
2 600
500
18 500
13 400
7 100
4 100
600
15.8
35.2
64.5
100
(
CaH
2
) and distilled before use.
a
1
b
Measurement. The solvents for 1H NMR measurement
Measured by H NMR. Determined by GPC measurement.
The corresponding entries in Table 1 were E, B, F, G, H, and I.
c
were CDCl and acetone-d . The solvent contained 0.5%
3
6
1
tetramethylsilane as the internal standard. H NMR spectra
were recorded on a Bruker DMX-300 spectrometer, working
at 300.130 MHz. FTIR spectra were recorded on Nicolet 560
benzene was evaporated, 5.89 g of crude RS-â-benzyl malolac-
tonate (MA) was obtained. The crude product was purified by
chromatography on silica gel twice with a solvent mixture of
dichloromethane and petroleum ether (90/10).
-
1
spectrometer over the wavenumber range 4000-400 cm
.
Differential scanning calorimetric (DSC) measurements were
made using TA DSC Q10. The procedure was as follows: first,
the samples were heated to 100 °C with the heating rate of 10
CL/MA Copolymerization. Prescribed amounts of CL and
MA with catalyst stannous octoate were put into polymeriza-
tion tubes. The tubes were degassed by several vacuum-
nitrogen gas purge cycles to remove oxygen and trace water.
The tubes were sealed under vacuum and placed into oil baths
at different temperatures for 24 h. The polymerization tubes
were broken in liquid nitrogen, and the polymers were dis-
solved in chloroform and then precipitated into large amounts
of a mixture of diethyl ether and petroleum ether. The white
protected PCLMA precipitates were dried under vacuum at
room temperature for 2 days.
-
1
°
°
C min (to eliminate thermal history) and then held at 100
C for 1 min; then the samples were cooled to -80 °C with a
-
1
cooling rate of 5 °C min , held at -80 °C for 1 min, and then
-
1
heated to 100 °C with a heating rate of 10 °C min . All the
scanning processes were under a nitrogen atmosphere. Mo-
lecular weight (M
n w
and M ) and molecular weight distribution
(
M
w
/M ) were determined with respect to polystyrene stan-
n
dards by gel permeation chromatography (GPC), and these
results were therefore used only as a qualitative tool to check
the peak shape and size distribution of the different polymers.
GPC was performed on an Agilent 1100 Series and analyzed
with GPC-SEC data analysis software. Samples were ana-
lyzed at 25 °C with tetrahydrofuran as eluent at a flow rate
Hydrogenolysis. 0.2 g of Pd/C (20%) was added to a
solution of 1 g of PCLMA in 100 mL of THF. The system was
2
bubbled with H and agitated continuously for 24 h. The Pd/C
was filtered off and washed with THF, the merged filtrate was
thickened by solvent evaporation, and the thickened solution
was dropped into a large amount of diethyl ether to precipitate
the deprotected copolymer. The deprotected PCLMAc precipi-
tates were dried under vacuum at room temperature for 2
days.
-
1
of 1.0 mL min
.
Synthesis of RS-â-Benzyl Malolactonate. The synthesis
1
6
of RS-â-benzyl malolactonate followed a published method.
9.7 g (0.1 mol) of RS-bromosuccinic acid was dried under
vacuum for 2 h, and 25 mL of THF was added under a N
1
2
atmosphere. The mixture was kept in an ice bath and stirred
vigorously for 30 min, and 20 mL (0.14 mol) of TFAA was
added slowly over 2 h. When the mixture was clear, the solvent
was evaporated with a rotary evaporator, and a kind of pale
yellow oil was left over. 10.8 g (0.1 mol) of distilled benzyl
alcohol was added immediately, and the system was stirred
vigorously at 45 °C for 12 h to give a bright yellow oil mixture.
The mixture was dissolved into 100 mL of diethyl ether,
washed with 100 mL of distilled water three times, and dried
HEMA Grafted PCLMAc. 11.6 g of deprotected PCLMAc
(entry d-G in Table 2), 0.46 g of HEMA, and 1.33 g of DCC
were added into a 100 mL bottom-rounded flask with a
magnetic stirrer and 60 mL of THF. The mixture was stirred
at room temperature for 24 h and filtered. The solution was
condensed and precipitated in a large amount of diethyl ether.
The viscous liquid was vacuum-dried at room temperature for
24 h.
UV Microembossing. 2 wt % of Irgacure 651 was added
in the HEMA-g-PCLMAc, and the mixture was stirred at 60
4
over MgSO /decolorizing charcoal. After filtration, the solvent
in the filtrate was evaporated to yield a colorless oil product.
A solution of 2 N NaOH was added to the colorless oil slowly
to adjust the pH to 7.2. The solution was heated to 45 °C, and
°
C. When Irgacure 651 was completely dissolved in the resin,
the resin was dispensed onto a surface micropatterned rubber
7
mold fabricated as previously reported. The resin on the
1
50 mL of benzene was added. After being stirred vigorously
for 3 h, the organic phase was washed with 150 mL of 5%
NaHCO aqueous solution twice and distilled water until
neutrality, and then it was dried over MgSO . After the
rubber mold was degassed in a vacuum at 60 °C for 30 min
and then irradiated with UV for 90 s using a PK102 UV
machine from I & J Fishnar Inc.; the area-averaged UV
3
2
4
intensity at 365 nm was adjusted to be 16 mW/cm . The

Macromolecules, Vol. 38, No. 20, 2005
Poly(ꢀ-caprolactone-co-RS-â-malic acid) 8229
Scheme 1. Synthetic Route of HEMA Grafted
Poly(E-caprolactone-co-RS-â-malic acid)
micropattern was examined using a scanning electron micro-
scope (SEM), specifically Joel JSM-5600.
Figure 1. GPC spectra of poly(ꢀ-caprolactone-co-RS-â-benzyl
malolactonate). The polymerization conditions were 130 °C
with 1/1000 catalyst concentration. The composition of MA in
the copolymers was (E) 0%, (B) 6.8%, (F) 16.2%, (G) 35.0%,
Results and Discussion
The purpose of the synthesis is to create a new
functional biodegradable UV microembossing resin,
which is useful in tissue engineering scaffold fabrication.
The synthetic steps of HEMA grafted poly(ꢀ-caprolac-
tone-co-RS-â-malic acid) UV microembossing resin are
shown in Scheme 1.
(
H) 64.7%, and (I) 100%.
CL/MA Copolymerization. A catalyst is needed for
the ring-opening copolymerization of ꢀ-caprolactone and
RS-â-benzyl malolactonate. Though the use of stannous
octoate [Sn(Oct)2] to catalyze the ring-opening polym-
erization of RS-â-benzyl malolactonate has not previ-
ously been reported, stannous octoate is an efficient and
biocompatible catalyst for ring-opening polymerization
of ꢀ-caprolactone; therefore, we chose Sn(Oct)2 to cata-
lyze the copolymerization of ꢀ-caprolactone and RS-â-
benzyl malolactonate. The effects of the temperature,
the monomer compositions, and the catalyst/monomer
ratios were studied.
Copolymerization was attempted at a range of reac-
tion temperatures from 90 to 170 °C with 1/1000 (molar
ratio) catalyst content and 12.2% (molar ratio) MA in
the feeding dose. Copolymerization failed at 90 °C but
was successful at 110, 130, 150, and 170 °C, with
varying copolymer properties (Table 1). The molecular
weights (Mn) of the resulting copolymers were 4700,
1
Figure 2. H NMR spectra of PCL (entry E), PCLMA (entry
F), and PMA (entry I). The solvent for sample E was CDCl
and the solvent for samples F and I was actone-d
3
,
6
.
position, which indicates that stannous octoate catalyzes
but does not initiate the copolymerization reaction.
The GPC spectra of poly(ꢀ-caprolactone-co-RS-â-ben-
zyl malolactonate) are shown in Figure 1. There are
residual oligomers in both the poly(ꢀ-caprolactone)
2
0 500, 13 800, and 12 100 (Table 1, entries A-D). The
MA proportion in the copolymers was 5.9, 6.8, 7.0, and
.3 mol %, much lower than those in the feeding dose.
6
Both the molecular weight and the yield were the
highest at the reaction temperature of 130 °C. The
polydispersity of the copolymers was 2.06, 1.42, 1.54,
and 1.44, respectively. In addition to maximizing MA
content, molecular weight, and yield, the 130 °C also
minimized polydispersity; it was selected for further
polymerization study.
(
entry E) and poly(RS-â-benzyl malolactonate) (entry I)
homopolymers. The eluent time of the copolymer in-
creased with increasing MA content, indicating de-
creased molecular weight. The calculated molecular
weights using polystyrene standards are summarized
1
in Table 1. Figure 2 shows the H NMR spectra of PCL,
With increase of the MA content in the feeding dose
from 12.2 (entry B) to 27.0 (entry F), 45.3 (entry G), and
PMA, and PCLMA. There are four different protons (h,
f, g, e in Figure 2) in the MA units. They produce peaks
at 7.3, 5.5, 5.2, and 2.9 ppm, respectively. The signal at
7.3 ppm (h) is due to the protons in the pendant benzene
ring (C6H5), the signal at 5.5 ppm (f) is from the proton
of CH in main chain, the signal of CH2 in pendant
groups appears at 5.2 ppm (g), and the signal at 2.9 ppm
(e) is due to the protons of CH2 in the main chains. The
CL segment contains five proton sites. Two of these,
COCH2CH2CH2 and CH2CH2CH2O, are in very similar
chemical environments and contribute to a common
signal at 1.6 ppm (b). The other three protons of COCH2-
CH2 (a), CH2CH2CH2 (c), and CH2CH2O (d) produce the
signals at 2.4, 1.4, and 4.0 ppm. The integrated areas
of the peaks of CH in MA at 5.5 ppm (f) and CH2CH2O
in CL at 4.0 ppm (d) were employed to calculate the
6
8.9 mol % (entry H), the molecular weight (Mn) of the
copolymer decreased from 20 500 to 13 400, 10 300, and
100, respectively. Variation of the MA content of the
8
feeding dose also strongly affected the MA content of
the resulting copolymers: 6.8 mol % (entry B), 16.2 mol
%
(entry F), 35.0 mol % (entry G), and 64.7 mol % (entry
H). The MA content in the copolymer increased with
the MA content in the feeding dose but at a slower rate.
The variation of the molecular weight and composition
demonstrates that the reactivity of ꢀ-caprolactone in this
copolymerization reaction is much higher than that of
RS-â-benzyl malolactonate. Reaction B was repeated
with varying catalyst content (entries J and K) with only
modest effect on copolymer molecular weight and com-

8230 He and Chan-Park
Macromolecules, Vol. 38, No. 20, 2005
Figure 5. FTIR spectra of poly(ꢀ-caprolactone-co-RS-â-malic
acid) with malic acid content (%): (d-I) 100, (d-H) 64.5, (d-G)
35.2, (d-F) 15.8, (d-B) 6.5, and (d-E) 0.
1
Figure 3. H NMR spectra of poly(ꢀ-caprolactone-co-RS-â-
6
malic acid) (entry d-H). The solvent was actone-d .
Figure 6. GPC spectra of poly(ꢀ-caprolactone) before (entry
E) and after (entry d-E) hydrogenolysis.
strong vibrational band, due to O-H in carboxyl groups,
Figure 4. FTIR spectra of poly(ꢀ-caprolactone-co-RS-â-benzyl
malolactonate) (entry F) and poly(ꢀ-caprolactone-co-RS-â-malic
acid) (entry d-F). The absorbance peaks of benzene are absent,
and the broad OH vibrational band of COOH is strong after
hydrogenolysis.
which extends across the wide wavenumber range
-
l
2
500-3500 cm . The changes in the spectra demon-
strate that the pendant benzyl groups were changed to
carboxyl groups by hydrogenolysis. Combined FTIR
spectra of poly(ꢀ-caprolactone-co-RS-â-malic acid) with
â-malic acid content varying from 100, 64.5, 35.2, 15.8,
6.5 to 0 mol % are shown in Figure 5. The strong
absorbance of O-H in carboxyl groups diminishes with
decreasing malic acid content.
composition of the copolymer; the derived compositions
are shown in Table 1.
Hydrogenolysis. The hydrogenolysis of poly(ꢀ-cap-
rolactone-co-RS-â-benzyl malolactonate) was carried out
in a hydrogen atmosphere with Pd/C as catalyst. The
solvent was very important to the hydrogenolysis; it was
needed to dissolve not only the PCLMA but also the
hydrogenolysized product PCLMAc. After trials of many
solvents, tetrahydrofuran was chosen as the solvent for
hydrogenolysis.
To study whether hydrogenolysis may entail degrada-
tion of the polymer chains, PCL homopolymer was
hydrogenolysized at the same conditions. The molecular
weight of PCL after hydrogenolysis was measured by
GPC (Figure 6). The GPC spectrum shows that the
molecular weight of PCL decreases after hydrogenolysis,
indicating degradation in the PCL main chain.
1
The H NMR spectrum of hydrogenolysized poly(ꢀ-
caprolactone-co-RS-â-malic acid) (entry d-H) is shown
in Figure 3. It is apparent that the signals of CH2 and
C6H5 in pendant benzyl groups at 5.2 and 7.3 ppm (g
and h in Figure 2) have vanished, while the other proton
signals in CL and MA units are unchanged. A new wide
and weak signal peak between 9.5 and 8.0 ppm (i in
Figure 3) appeared and is attributed to the proton of
COOH in pendant groups.
The composition and molecular weight of PCLMAc,
which was hydrogenolysized from PCLMA, are shown
in Table 2. The content of malic acid in PCLMAc was
nearly the same as the content of â-benzyl malolacto-
nate in the corresponding PCLMA. The molecular
weight of PCLMAc was 55 300, 11 600, 8500, 4400,
2600, and 500 for the malic acid content of 0, 6.5, 15.8,
35.2, 64.5, and 100 mol %, respectively. Each PCLMAc
had a lower molecular weight than the corresponding
PCLMA due to the removal of benzyl groups and the
degradation of the main chain.
The FTIR spectra of PCLMA and PCLMAc are shown
in Figure 4. In protected PCLMA copolymer (entry F in
Table 1), the characteristic benzene ring absorbance
-1
peaks are at 700, 742, and 1502 cm wavenumber. The
deprotected PCLMAc (entry d-F of Table 2) spectrum
lacks benzene ring absorbance peaks but exhibits a
Thermal Properties of PCLMA and PCLMAc.
Thermal properties such as Tg and Tm of the function-
alized biodegradable polyesters are very important for

Macromolecules, Vol. 38, No. 20, 2005
Poly(ꢀ-caprolactone-co-RS-â-malic acid) 8231
Figure 7. DSC spectra of poly(ꢀ-caprolactone-co-RS-â-benzyl
Figure 8. DSC spectra of poly(ꢀ-caprolactone-co-RS-â-malic
acid): (A) with cooling temperature rate 5 °C/min; (B) with
heating temperature rate 10 °C/min. The malic acid content
malolactonate): (A) with cooling temperature rate 5 °C/min;
(B) with heating temperature rate 10 °C/min. The MA content
%) was (E) 0, (B) 6.8, (F) 16.2, (G) 35.0, (H) 64.7, and (I) 100.
(
(
%) was (E) 0, (B) 6.5, (F) 15.8, (G) 35.2, (H) 64.5, and (I) 100.
Table 3. Thermal Properties of
DSC spectra of PCLMAc during the cooling and heating
processes are shown in Figure 8. Like the spectra in
Figure 7A, crystallization peaks appear in the entries
d-E and d-B, which are the corresponding copolymers
to entries E and B. There are some differences between
the deprotected and protected copolymer scans. The
exothermal crystallization peak of entry d-B in Figure
8A is much sharper than that of entry B in Figure 7A.
The weak endothermal melting peak of the entry F
heating scan (Figure 7B) is absent in d-F (Figure 8B),
and the endothermal melting peak in entry d-B is split
into two peaks, a weaker peak at 38 °C and a stronger
peak at 43 °C.
Poly(E-caprolactone-co-RS-â-benzyl malolactonate) and
a
Poly((E-caprolactone-co-RS-â-malic acid)
Tg (°C)
Tc (°C)
Tm (°C)
P2c
59 58
38 43 (38) 37.15 40.31
23 1.69
∆H (J/g)
P1b P2c
54.06 61.24
entries P1b P2c P1b P2c P1b
E/d-E
B/d-B
F/d-F
-56 -57
-49 -38 -4
-43 -33
31
31
7
G/d-G -25
-5
26
33
H/d-H
I/d-I
5
14
a
Determined by GPC measurement. b PCLMA. c PCLMAc.
processability. Figure 7 shows the DSC spectra of
PCLMA with different MA content. Figure 7A shows
the spectra of the cooling process from 100 to -80 °C.
The copolymer (entry B) with 6.8 mol % MA content
crystallized, but the crystallization peak is much wider
and weaker than that of PCL homopolymer (entry E).
No crystallization peaks appeared when the MA content
was increased from 16.2 (entry F) to 100% (entry I). The
absence of crystallinity in the higher MA content
copolymers (Table 3) is attributed to the disruption of
the regularity of PCL and its large sterically hindrant
benzyl pendant groups. Figure 7B shows the thermal
behavior of PCLMA in the heating process as the
temperature increases from -80 to 100 °C. Three
copolymers, entries E, B, and F, have endothermal
melting peaks; the peak in entry F is very weak. The
The thermal properties of PCLMA and PCLMAc are
summarized in Table 3. The glass transition tempera-
ture (Tg) of both PCLMA and PCLMAc increases when
MA content increases from 0 to 100 mol % (Table 3).
The Tg of PCLMA is -56 °C (entry E), -49 °C (entry
B), -43 °C (entry F), -25 °C (entry G), 5 °C (entry H),
and 14 °C (entry I) with the corresponding MA content
of 0, 6.5, 15.8, 35.2, 64.5, and 100 mol %, respectively.
The Tg of corresponding PCLMAc is -57 °C (entry d-E),
-38 °C (entry d-B), -33 °C (entry d-F), -5 °C (entry
d-G), 26 °C (entry d-H), and 33 °C (entry d-I). PCL
homopolymer is a semicrystalline polymer with Tg of
-56 °C (entry E, Table 3). Poly(RS-â-benzyl malolacto-
nate) (PMA) homopolymer is an amorphous polymer
with Tg of 14 °C (entry I, Table 3). The Tg of PMA is
higher than that of PCL, so the increase of PCLMA Tg

8232 He and Chan-Park
Macromolecules, Vol. 38, No. 20, 2005
with MA content is expected. Similarly, the Tg of PMAc
homopolymer is 33 °C, higher than PCL homopolymer,
leading to the higher Tg of PCLMAc copolymer with
increased MAc content. Both the protected and depro-
tected copolymers exhibit a single glass transition
temperature, demonstrating that these polymers are
indeed copolymers of ꢀ-caprolactone and RS-â-benzyl
malolactonate or RS-â-benzyl malic acid rather than
mixtures of the homopolymers of poly(ꢀ-caprolactone)
and poly(RS-â-benzyl malolactonate) or poly(RS-â-ben-
zyl malic acid). DSC results show that all the function-
alized copolymers are liquid at 50 °C. These materials
are potentially suitable for tissue engineering scaffold
fabrication by UV microembossing.
The inter- and intramolecular interactions of PCLMAc
and PCLMA are different. The pendant carboxyl groups
of PCLMAc have small steric hindrance compared to
benzyl groups of PCLMA. In PCLMAc, inter- and
intramolecular hydrogen bonds exist between pendant
carboxyl groups. These hydrogen bonds strengthen the
interaction between polymeric chains. This accounts for
the higher Tg, Tm, and ∆H of PCLMAc compared to
those of the corresponding PCLMA (Table 3) and the
sharper exothermal peak of PCLMAc (entry d-B) than
that of PCLMA (entry B). The appearance of two endo-
thermal peaks in entry d-B is also attributed to the
1
6
formation of hydrogen bonds. The hydrogen bonds
hamper the movement of the main chains and limit
them in certain domains; thus, PCL segments in co-
polymer crystallize imperfectly in these domains. The
imperfect PCL crystals lead to two endothermic peaks.
The degradation in hydrogenolysis also affects the
crystallization of PCLMAc. The molecular weight (Mn)
of PCL homopolymer decreases from 95 700 (entry E,
Table 1) to 55 300 (entry d-E, Table 2) with hydro-
genolysis. The ∆H of PCL increases from 54.06 J/g
Figure 9. Temperature-dependent FTIR spectra of O-H
stretching region in poly(ꢀ-caprolactone-co-RS-â-malic acid):
(A) entry d-I; (B) entry d-G.
(
entry E) to 61.24 J/g (entry d-E) due to the increased
mobility of PCL chains of lower molecular weight (Table
3
). Similarly, the ∆H of PCLMA (entry B) increases from
3
7.15 to 40.31 J/g after removal of the benzyl groups.
The disappearance of an endothermal melting peak in
entry d-F is also attributed to the degradation that
occurs in hydrogenolysis; the degradation lowers the
molecular weight of copolymer so much that it can no
longer crystallize (Figure 8B).
FTIR is an effective method for the study of polymer
2
1-24
interactions, especially hydrogen bonding.
This
technique was applied to our new copolymers to better
characterize their structure. FTIR spectra were obtained
at a range of temperatures from room temperature
(
about 22 °C) to 100 °C. The FTIR spectra of the O-H
stretching band of PCLMAc are shown in Figure 9. The
-
1
free vibrations of O-H around 3500 cm weaken and
the H-bonded O-H vibrations strengthen around 3200
Figure 10. FTIR spectra of the carbonyl region in poly(ꢀ-
caprolactone-co-RS-â-benzyl malolactonate) (G) and poly(ꢀ-
caprolactone-co-RS-â-malic acid) (d-G).
-
1
cm as the temperature increases from 22 to 100 °C in
PCLMAc d-I. There is no change with temperature in
PCLMAc d-G. The observed behaviors of the spectra are
attributed to the glass transition. Below the glass
transition temperature, the polymeric chains are frozen,
the pendant functional groups cannot move freely, and
it is more difficult for O-H groups to form hydrogen
bonds, so that their IR absorbance peaks appear around
transition temperature of PCLMAc d-I is 33 °C, and its
IR absorbance spectra in the O-H band exhibit changes
in keeping with the above interpretation. The glass
transition temperature of PCLMAc d-G is -5 °C, below
the lowest temperature at which spectra were obtained,
and the O-H band spectra exhibit essentially no varia-
tion with temperature.
-
1
3
500 cm . At temperatures above Tg, the copolymer is
in an elastic state, the mobility of polymeric chains is
enhanced, and more hydrogen bonds are formed, so that
the IR absorbance in the H-bonded O-H stretching
The FTIR spectra of the carbonyl region (CdO) in
PCLMA (entry G) and PCLMAc (entry d-G) are pre-
-
1
sented in Figure 10. There is one peak at 1727 cm in
-
1
-1
band around 3200 cm is strengthened. The glass
protected PCLMA. A shoulder peak at 1703 cm

Macromolecules, Vol. 38, No. 20, 2005
Poly(ꢀ-caprolactone-co-RS-â-malic acid) 8233
1
.10 ppm (j). They are attributed to the protons of Cd
CH2, CH2CH2, and -CH3 in HEMA. Because of the
effect of unsaturated carbon double bond, the protons
in CdCH2 split into several peaks, which were located
at 6.10 and 5.65 ppm (at the left of peak f). The protons
in CH2CH2 also split into multipeaks located from 4.30
to 4.55 ppm. The intensity of peak j was chosen to
calculate the content of HEMA grafting, and 10% of
â-malic acid was grafted HEMA, which coincided with
the feeding dose. It means that the efficiency of HEMA
grafting was very high with DCC as catalyst. The malic
acid content in d-G is 35.2% (Table 2), making the
content of HEMA in the total polymer to be 3.5%.
The UV microembossing of HEMA-g-PCLMAc was
carried out under UV irradiation with 2% Irgacure 651
as photoinitiator. Two molds PDMS rubbers were used
as molds for UV embossing. The micropatterns fabri-
cated were 120 × 60 × 25 and 80 × 60 × 25 µm (channel
width by channel depth by wall width). The SEMs of
UV microembossed HEMA-g-PCLMAc are shown in
Figure 12. The resin filled the microcavities, replicated
the mold, and cured well and has sufficient mechanical
strength to enable demolding without distortion.
Figure 11. 1H NMR spectra of HEMA grafted poly(ꢀ-capro-
lactone-co-RS-â-malic acid).
appears in the deprotected PCLMAc. The two CdO
-
1
vibrational peaks centered at 1727 and 1703 cm are
attributed to vibration of free and hydrogen-bonded
carbonyl groups, respectively. Since malic acid with
carboxylic acid group is the minor constituent, there are
not enough OH groups to form hydrogen bonds with all
carbonyl groups. Therefore, both free and hydrogen-
bonded carbonyl groups exist in deprotected PCLMAc.
Conclusion
We synthesized a functionalizable and photopattern-
able HEMA grafted poly(ꢀ-caprolactone-co-RS-â-malic
acid) resin. The random ring-opening copolymerization
of ꢀ-caprolactone and RS-â-benzyl malolactonate using
stannous octoate catalyst to produce liquid polymers
1
UV Microembossing of HEMA-g-PCLMAc. The H
NMR of HEMA grafted PCLMAc is shown in Figure 11.
1
Comparing with the H NMR of PLMAc, it is obvious
that three new peaks appeared at 6.10 (k), 4.38 (i), and
Figure 12. UV-microembossing SEM of HEMA grafted poly(ꢀ-caprolactone-co-RS-â-malic acid). (A) and (B) are surface and cross
section of UV microembossing with 120 µm channel width, 60 µm depth, and 25 µm wall width. (C) and (D) are surface and cross
section of UV microembossing with 80 µm channel width, 60 µm depth, and 25 µm wall width.

8234 He and Chan-Park
Macromolecules, Vol. 38, No. 20, 2005
was systemically studied. The reactivity of ꢀ-caprolac-
tone in copolymerization was higher than that of RS-
â-benzyl malolactonate. The molecular weight and glass
transition temperature (Tg) of the copolymers decreased
with increasing ꢀ-caprolactone content. The protective
benzyl groups were removed completely in hydrogenoly-
sis, but some main chain degradation occurred. FTIR
spectra showed that hydrogen bonds formed in the
functionalized copolymers. The Tg, Tc, and Tm of PCLMAc
were higher than those of corresponding PCLMA due
to the hydrogen bonds in PCLMAc. The liquid HEMA
grafted poly(ꢀ-caprolactone-co-RS-â-malic acid) was shown
to be a suitable liquid resin for UV microembossing. It
has potential applications in tissue engineering scaffold
fabrication.
(6) Thompson, D. M.; Buettner, H. M. Tissue Eng. 2001, 7, 247.
(
(
(
7) Yan, Y. H.; Chan-Park, M. B.; Gao, J. X.; Yue, C. Y. Langmuir
2004, 20, 1031.
8) Chan-Park, M. B.; Yan, Y. H.; Neo, W. K.; Zhou, W. X.; Zhang,
J.; Yue, C. Y. Langmuir 2003, 19, 4371.
9) Jin, Y.; Shen, M. B.; Chan-Park, Z. Q.; Feng, V. C.; Zhi W. F.
J. Biomed. Mater. Res. B, in press.
(10) Bear, M. M.; Lozac’h, K.; Randriamahefa, S.; Langlois, V.;
Bourbouze, R.; Guerin, P. Polymer 1999, 40, 6521.
(
(
(
11) Osanai, S.; Nakamura, K. Biomaterials 2000, 21, 867.
12) Vert, M. Polym. Degrad. Stab. 1998, 59, 169.
13) Bizzarri, R.; Chiellini, F.; Solaro, R.; Chiellini, E.; Camass,
S.; Guerin, P. Macromolecules 2002, 35, 1215.
(
14) Coulembier, O.; Degee, P.; Cammas, S.; Guerin, P.; Dubois,
P. Macromolecules 2002, 35, 9896.
(15) He, B.; Wan, Y.; Bei, J. Z.; Wang, S. G. Biomaterials 2004,
5, 5239.
2
(
16) He, B.; Bei, J. Z.; Wang, S. G. Polymer 2003, 44, 989.
(
17) Kuo, S. W.; Lin, C. L.; Chang, F. C. Macromolecules 2002,
Acknowledgment. This research was supported by
35, 278.
an A-STAR (Singapore) grant (Project No. 022 107
(18) Hubbell, J. A. Curr. Opin. Biotech. 1999, 10, 123.
(19) Langer, R. J. Controlled Release 1999, 62, 7.
(20) Yamaoka, T.; Hotta, Y.; Kobayashi, K.; Kimura, Y. Int. J.
Biol. Macromol. 1992, 25, 265.
0
004).
References and Notes
(
(
(
21) Sato, H.; Murakami, R.; Padermshoke, A.; Hirose, F.; Senda,
K.; Noda, I.; Ozaki, Y. Macromolecules 2004, 37, 7203.
22) Iriondo, P.; Iruin, J. J.; Fernandez-Berridi, M. J. Macromol-
ecules 1996, 29, 5605.
(
1) Kulkarni, R. K.; Pani, K. C.; Neuman, C.; Leonard, F. Arch.
Surg. 1966, 93, 839.
(
2) Gilding, D. K.; Reed, A. M. Polymer 1979, 20, 1459.
3) Gilding, D. K.; Reed, A. M. J. Biomed. Mater. Res. 1971, 5,
(
23) Dong, J.; Ozaki, Y. Macromolecules 1997, 30, 286.
169.
(
4) Pulapura, S.; Kohn, J. J. Biomater. Appl. 1992, 6, 216.
5) Shin, M.; Matsuda, K.; Ishii, O.; Terai, H.; Kaazempur-
Mofrad, M.; Borenstein, J.; Detmar, M.; Vacanti, J. P.
Biomed. Microdevices 2004, 6, 269.
(24) Li, D.; Brisson, J. Macromolecules 1996, 29, 868.
(
MA050545J