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TYPE: Article CC:CCL
JOURNAL TITLE: Macromolecular symposia
USER JOURNAL TITLE: Macromolecular Symposia
ARTICLE TITLE: Crosslinked copolymers with degradable oligo(lactide) branches
ARTICLE AUTHOR: Barbara Sandner, Simone Steurich and Siegfried War
VOLUME: 103
ISSUE: 1
MONTH: January
YEAR: 1996
PAGES: 149–162
ISSN: 1022-1360
OCLC #:
Processed by RapidX: 12/17/2015 6:22:37 PM
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Macromol. Symp. 103,149-162 1996)
149
CROSSLINKED COPOLYMERS WITH DEGRADABLE
OLIGO(LACTIDE)
BRANCHES
Barbara Sandnee, Simone Steurich
Martin-Luther-UniversitiitHalle-Wittenberg
Fachbereich Chemie, Geusaer Str., 06217 Merseburg, Germany
Siegfried Wartewig
Martin-Luther-UniversitiitHalle-Wittenberg
Fachbereich Physik, Hoher Weg 7,06120 Halle, Germany
Abstract: Methods for preparation of oligo(lact0ne) macromonomers end-capped
with methacrylate groups are summarized. The conversion of C=C double bonds
during the crosslinldng copolymerization of the macromonomers has been studied
by means of Laser
Raman
spectroscopy at room temperature. Glass transition,
mechanical properties and the degradation rate of composite materials prepared by
copolymerization in the presence of hydroxylapatite may systematically be
influenced both by the type of lactone monomer, e.g. D,L- or L,L-dilactide,
diglycolide, and the comonomer, e.g. 2-hydroxyethyl methacrylate, tetrahydro-
furfuryl methacrylate, ri(ethy1ene glycol) dimethacrylate.
The composites should be useful as bone implant materials with lower
polymerization exotherm and better biocompatibility than conventional materials
based on methyl methacrylate.
INTRODUCTION
The biodegradable polyesters of various lactones are of special interest for medical applications
because products of degradation, e.g. lactic and glycolic acid, occur in human metabolism.
1996 Huthig & Wepf Verlag, Zug
CCC
1022-1360/95/$04.00
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151
&oxide of Cisopropenylbenzyl alcohol were not satisfactory. The initiation rate was low
compared to the rate of the propagation reaction resulting in macromonomers with broad
niolecular weight distribution.
The aluminium monoakoxide prepared by the reaction of triethylaluminium with 2-hydroxy-
ethyl methacrylate (HEMA)
has
proved as a suitable and very effective initiator for the
polymerization of both e-caprolactone (Ref. 8) and D,Ldilactide (Ref.
9).
According to Ph.
Dubois et
al.
(Refs.
8, 9),
the mechanism of these lactone polymerizations involves the
coordination of the lactone at the aluminium &oxide group followed by the lactone insertion
into the weakened Al-oxygen bond. The molecular weights predictable from the ratio of
monomer and initiator at complete conversion, as well as the relatively narrow molecular
weight distribution
m,.,m.
.2) of the macromonomers, support the assumption of a living
polymerization. The polymerization reaction was stopped by addition of aqueous HCl forming
the a-methacryloyl, whydroxy-oligoflactone) macromonomer. The Go-dimethacryloyl-
oligoflactone) was obtained by termination with methacryloyl chloride. Amphiphilic graft
copolymers and amphiphilic copolymer networks were obtained by copolymerization of the
a-
mono- and the Gwdimacromonomer, respectively, with HEMA.
However, the methods of macromonomer synthesis mentioned here, include multistep
reactions, also the preparation of the diethylaluminium &oxide of HEMA and the
polymerization of the lactone initiated by this &oxide have to
be
performed in an organic
solvent (Refs.
7,
8).
Broadly such reaction conditions seem a relatively unsuitable prerequisite
to apply ta oligo(1actone) macromonomers for medical purposes, therefore, we have used the
initiation
of
the lactone polymerization by alcohols catalyzed both by Lewis bases (Ref. 10) as
well as Lewis acids as described in Ref. 11. Various P-hydroxyesters of methacrylic acid have
been found by us to act as effective initiators of the oligomerization, e.g. of L,L- and D,L-
dilactide, diglycolide and e-caprolactone. We report here the crosslinking copolymerization n
the presence of inorganic fillers, their degradation behaviour and some thermal and mechanical
properties.
EXPERIMENTAL PART
Materials
2-Hydroxyethyl methacrylate (HEMA), tetrahydrofurfuryl methacrylate
(THFM),
tri(ethy1ene
glycol) dimethacrylate (TEGDMA)
(all
from Riihm Chemische Fabrik GmbH) were used as
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152
received. BisphenolA-bis 2-hydroxypropylmethacrylate) (Bis-GMA) was synthesized as
described in Ref. 12. Hydroxylapatite (Osprovit) (Cerasiv GmbH ) was silanized with
1
wt.- %
trimethylsilylpropyl methacrylate (Fluka AG) in acetone.
L,L-
nd D,L-dilactide (Boehringer
Ingelheim KG) were purified by recrystallization from ethyl acetate (distilled over calcium
hydride) and dried over P4010
in
vacuo.' Glycolide (Boehringer Ingelheim KG),
N-
vinylimidazole (Riedel-de Haen AG), Sn(II)octoate (Sigma Chemical Co.) and MgO
(Laborchemie Apolda) were used as received. Dibenzoyl peroxide (DBPO) was recrystallized
from chloroform. N,N-dimethyl-p-toluidineDMpT) was distUed under vacuum in an argon
atmosphere.
Synthesis of macromo nomers
Macromonomers were synthesized by reaction of D,L-dilactide, L,L-dilactide or mixtures of
L,L-or D,L-dilactide with diglycolide
in
a m olar ratio
of 7:3
with 9.09 mol-% Bis-GM A, using
0.56
mol-% Mg O as a catalyst. The m ixture was stirred at
130 C
for about 2 hours until
a l l
dilactide and diglycolide had reacted co mpletely. The molar m asses were controlled by m eans
of gel-penneation chromatography (GPC).
Preparation of composites
Com posites were prepared by chemically curing mixtures of the m acromono mer with HE MA ,
TEGDMA or
THFM
in a ratio 7:3 by weight
in the
presence of
45
wt.-% silanized
hydroxylapatite at
37
C for 24 h.
Initiator DBPO (0.4 wt.-% related to the whole monomer mixture) was added
to
one half of
the monomer mixture, with the activator DMpT in equimolar amount added to the other half.
Time from start of mixing to setting was ab out
10
min.
Analysis
GPC
The gel-permeation chromatography measurements were carried out
on
a Knauer device
equipped w ith a K nauer differential refractometer. For determination of the molecular weight
three
Hibar
RT
columns (PS I, PS4, PS20) and for
analyzing
the extracts two Waters Styragel
HR1 columns were used. Tetrahydrofuran (THF)erved as solvent. The mo lecular weight w as
calibrated relatively to m onodisperse polystyrene.
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153
Laser Ram an spectroscopy
Raman spectra were recorded with a Bruker Fourier transform infra-red spectrometer
IFS 66
equipped with the
Raman
module
FRA 106.
A diode pumped Nd:YAG laser which emits
radiation at
1064
nm was used as the excitation source. The scattered radiation was collected
at
180
to the source. Typical spectra were recorded at a laser power of 300 mW at sample
location and a resolution of 4
an-'. n
order to obtain a good signal to noise ratio, typically,
200
scans were avaraged.To monitor the curing of monomer mixtures, spectra were recorded
every 21 s after a handling time of about
50
to 80 s with 5 scans.
The manipulation and evaluation of the spectra were carried out using the Bruker OPUS
soilware package. Generally, Raman intensities were determined as integrated band intensities.
Monomer conversion
Pulverized samples (about 0.5 g) were shaken in THF for 8 hours at room temperature.
Insoluble components were separated to determine the conversion. The extract was analyzed
by GPC to determine the proportion, of macromonomer to the comonomers
HEMA
and
THFM,
respectively.
Dynamic mechanical analysis (DMA)
Dynamic mechanical analysis was performed on a Perkin Elmer DMA 7 in parallel plate mode
at a frequency of 1.00
Hz
with a dynamic stress of
800
mN and a static stress of 1200 mN. The
heating rate was Clmin.
Micro hardness
Microhardness was measured on a Fischerscop H 100 using a Vickers diamond. Composites
were tested at 22 C at a force of 1000mN for 14.5 s.
Diametral tensile strength
Samples (6 mm diameter d, 3 mm thickness t) cured at
37 C
for 24 h were measured on a
tcnsile testing machine (M30K by
J. J.
Lloyd I n s k e n t s ) with a 30
kN
load cell.
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The sample was
diametrally
placed
on
a steel cylinder. The steel cylinder of the crosshead was
lowered at 0.5 rmn mn onto the sample until contacting. Then the speed was increased to
10
m i n and the sample was loaded until fracture. At least 6 samples were tested.
The load F at fracture was used to calculate the diametral tensile strength
CTT
2 F
Degradation
Cured samples, 2
mm
in thickness, 10 mm
in
depth and 15
mm
in length, were stored
in
a
buffered solution
@H 7.4,
citric acid/sodium dihydrogenphosphate buffer) at
37
C. Every week
the solution was renewed. The released acid
in
the removed solution was determined by
potentiometric titration with 0.05 M KOH.
RESULTS
AND DISCUSSION
Synthesis of macromonomers
Bis-GMA has been proved by our studies to be an effective initiator for the oligomerization of
L,L- and D,Ldilactide as well as their cooligomerization with diglycolide according to the
following general reaction scheme:
130°C.
2-6
h
v
c=o
I
CH-CHI
=o
FH-CH?
, O n
-
H
H
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The macromonomers prepared with n = 10 are hard and brittle solids at room temperature.
They soften becoming highly viscous liquids at about 40 C.
Fig.
1
shows as an example the increase in number-average molecular weight
n
of oligo(L,L-
1actide)s against the time. Oligomerization was initiated with Bis-GMA and catalyzed by
N-
vinylimidazole (NVI), MgO and Sn(JI)octoate, respectively, as well as without my additional
catalyst.
Concerning the latter case, it must be noted that Bis-GMA was prepared
using 0.8
mol-% of
NVI
as a catalyst, therefore, there is some catalyst present also for the subsequent
oligomerizationof L,L-dilactide.
Mn calculated from the ratio of dilactide to Bis-GMA initiator, was obtained at 130 OC after
2
to 6 hours reaction time depending on the type and the content of the catalyst (Fig. 1).
0 1 2 3 4
Time / h
Fig. 1. Synthesis of macromonomers from Bis-GMA and L,Ldilactide (1:lO mol/mol), at
130 OC,@ talc. = 2000 g mor'. Mole ratios
of
Bis-GMA to catalyst: ---0--- 1 : 0.3
NVI,
O 1
:0.2
MgO,
0 :
0.03 Sn(I1) octoate,---*---ithout catalyst
Stannous octoate, the most commonly used catalyst for the polymerization of dilactides, is
obviously also the most effective one for the synthesis of the macromonomers (Fig. 1).
Additionally, Snm) octoate does not cause any racemization during the oligomerization of L,L-
dilactide; this may be a further advantage. However, from the medical point of view, MgO and
NVI (the latter can be incorporated by copolymerization nto the polymer network) should be
preferred.
Differences between Gn calculated and a n ound experimentally by
GPC
(Fig. 1) may
be
caused by the inappropriate calibration with polystyrene and
/
or by the depolymerization
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reaction. The molecular weight distribution calculated from the GPC measurements was
relatively narrow with
a,,,
/a, = 1.2 to 1.3.
Crosslinking copolymexization of oligoflac tide) macromonom ers
Macromonomers from Bis-GMA with dilaaide
(1:lO
mol/mol) as well
as
dilactide and
diglycolide (1:7:3 mol/mol) were copolymerized with HEMA, THFM and TEGDMA,
respectively,as diluent com onomers. The redox system DBPO -DMpT was used as an initiator
at room temp erature.
Fig. 2 shows the differences of the Laser Raman spectra between a macromonomer - HEMA
mixture and its copolymer obtained by curing initiated with DBPO at 80 C without inorganic
filler.
The
expected decrease of the intensity of the C-C stretching vibrational band at 1640
cm-'CH2= twisting vibration) and 1719 cm (C=O band of the methacrylate monomers) is
clearly visible. The bands a t 1640 and 1719
an-',
ith the aromatic CH= band at 1455
an-
s
the reference were chosen to determine the conversion of the methacrylate
C=C
double bonds
during the polymerization reaction.
Wavenumber/cm-'
Fig. 2. Laser Raman spectra of a m acromonomer
- HEMA
mixture
(7:3
W w t) (curve
1)
and
its copolymer (curve 2 ) heat cured with 0.5 w t . 4 D BPO a t 80 C for
2
h without fiuer
The
decrease of the band intensities monitored during the redo x initiated curing cycle is shown
in Fig.
3
at
various
times
at
24°C.
The
course
of
po lyrn eht ion could not
be
followed
in
the
presence of hydroxylapatite, because its
Raman
bands overlap those
of
the monomers and
polymers. However, quartz powder does not show any bands in the frequency region of
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157
interest. Therefore, it was used as the filer for the
Raman
spectroscopic
studies
of composite
curing.
v1
r
-
E
.-#
-
Wavenumber/cm-'
Fig.
3.
Laser
Raman
spectra of a macromonomer - HEMA 7:3 wt/wt) copolymedtion with
0.4 wt.-% DBPO and 0.22wt.- DMpT at 24 C.without filler.
Curing times: curve
1:
0
s,
curve 2: 195 s, c w e 3: 216
s,
curve 4: 237
s,
curve
5: 300 s
The increase of the C=C ouble bond conversion, calculated from the
simultaneous
decrease in
intensity of the
two
bands at 1640 an-' nd 1719 an- , n the curing time of a composite,
indicates that both bands give the
same
result (Fig. 4). The conversion is extraordinarilyhigh,
being greater than
90
%
compared
to
about
50
%
with dental
filling
composites containing Bis-
GMA
nd TEGDMA (Ref. 13).
However, the content
of
residual monomers in composites should
be
evaluated as a more
significant characteristic for medical purposes. The overall conversion of monomers in
composites from both the L,L- and D,L-dilactide macromonomers wfth different diluent
monomers was found to be 65 to
84
% (by extraction Table 1).The composition of the extract
was determined by
GPC
and also given in Table 1 indicating that the low molecular weight
comonomersHEMA and
THFM
espectively, were almost completely 2 6 %) incorporated
into the organic network matrix. In contrast, the conversion of the macromonomer was only
about70
%.
This result explains the high conversion of C=C ouble bonds observed by Raman
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158
spectroscopy, because the weight content
of
C=C double bonds
of
the macromonomer is
comparatively low.
Conversion
1
Curing time /seconds
Fig.
4.
Curing of Bis-GMA
-
D,L-dilactide
-
macromonomer (molar ratio 1
:
10) with HEMA
(macromonomer :
HEMA
= 7
: 3
by weight, 0.4 wt.-% DBPO, 45 wt.-%
silanized
quartz
powder, at
23
C
).
Conversion of C=C doub le bonds, calculated from --- ----=C band at
1640 cm-',
---0----
C=O
band at 1719 cm-'
Properties
of
composites with crosslinked oligo(1actide) methacrylates
The glass transition temperatures
TO
f the composites were obtained by DMA. Composites
with HEMA show the highest
TG
Table 1).
This
is consistent with the differences between T G
of
HEMA and THFM homopolymers as well as the lower overall conversion of monomers in
composites with TEGDMA. Accordingly, the composites with HEMA also have a larger
microhardness than those obtained with TEGDMA. However, the elastic moduli E given
in
Table 1 and calculated from the m icrohardness measurements, d o not differ between the three
types of composites, within the
limits
of the experimental error. The composites with
TEGDMA possess a higher diametral tensile strength than the other two, which is obviously
caused by the crosslinking effect of TEGD MA .
Distinctions between the com posites were also observed regarding their degradation behaviour
(Fig. 5 and 6). The composites with the more hydrophilic HEMA monomer degrade more
rapidly when the macromonomer branches contain only D,L-
or
L,L-dilactide, furthermore, the
introduction
of
diglycolide into
the
branches results not only in the expected increase of the
degradation rate, but also the differences between the copolymers with HEMA and
THFM
disappear. A higher degradation rate of composites with oligo(D,L-lactide) branches
as
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159
compared with those with oligo(L,L-lactide) branches was observed corresponding to the
behaviour
of
the homopolymers.
Table 1. Composition and properties
of
composites obtained from Bis-GMA - lactide
1:lO
mol/mol) macromonomers with TEGDMA,
HEMA
and THFM
7 : 3
wt/wt) by redox
initiated polymerization
0.4
wt.-% DBPO rel. to monomers) in the presence
of 45
wt.-%
silanized hydroxylapatite at room temperature
Type of
lactide Diluent monomers
macromonomer TEGDMA HEMA THFM
Overall conversion LL
of
monomers /% DL
Conversion
/% of
LL
-
Macromonomer DL
- Diluent LL
DL
wt.-% Macromonomer
LL
in copolymer DL
TGPC
LL
DL
Microhardness MPa LL
DL
E - modulus /GPa LL
DL
Diametral tensile strength /MPa DL
40 wt.-
diluent,
52.5
wt.-% hydroxylapatite)
70.0
65.3
62.4
71.0
212
213
4.5
4.8
13.8
74.3
78.2
64.8
70.3
96.4
96.5
61.1
63.0
71.8
79.2
262
264
4.8
5.1
8.5
83.6
80.0
77.6
72.7
97.6
97.1
65.0
63.6
57.0
68.3
263
2 17
4.6
5.1
8.7
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Released ac id /%
50
T i m e / d ay s
Fig. 5 In vitro degradation of copolymer composites from Bis-GMA endcapped
macromonomers
(1:lO
mol/mol)
--- ---
,L-dilactide,
---0---
L,L-dilactide and
---.--
,L-
dilactide and glycolide 7:3 mol/mol) with HEMA (7 ; wt/wt), 45 wt.-% silanized hydroxyl
apatite, stored in citric a c i d phosphate buffer solution (pH
7.4)
without enzymes, at
37
OC
Released ac id /%
T i m e / d a ys
Fig. 6 In vitro degradation of copolymer composites from Bis-GMA endcapped
macromonomers
(1:
10 mol/mol) --- ---,L-dilactide, ---o---L,L-dilactide and
.
,L-
dilactide and glycolide
7:3
mol/mol) with THFM
(7
:
3 wt/wt),
45
wt.-% silanized hydroxyl-
apatite, stored in citric acid/ phosphate buffer solution (pH 7.4) without enzymes, at 37 C
CONCLUSIONS
A conv enient method of synthesis for m acromonom ers of oligo(1actide)s and also coo ligomers
with diglycolide both endcapped with methacrylate groups, e.g. of Bis-GMA, has
been
developed. The redox initiated copolymerization of these macromonomers with the
biocompatible comonomers HEM A,
THFM
and TEGDMA, respectively, in the presence of
inorganic fillers results
in
290
%
conversion of C=C double bonds, and 70
-
80 % conversion
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(10)
1
1)
H. R. Kricheldorf,
J.
Meier-Haack, Makromol. Chem. 194 ,7 15 (199 3)
DE 29
14
988 (1980).
Consortium f i i
elektrochemische Industrie GmbH,
invs.: K.
Marquardt;
Chern.
Abstr
9 4 , 6 6 4 2 4 ~1981)
B.
Sandner,
R.
Schreiber, Makromol. Chem. 193 ,2 763 (199 2)
B.
Sandner,
R.
Schreiber,
U.
Matschinske, 2nd Dresden Polymer Discussion. 1988.
Preprints L 31, p. 181
(12)
(13)