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Synthesis and Properties of Graft Copolymers Based
on Poly(3-hydroxybutyrate) Macromonomers
Sophie Nguyen, Robert H. Marchessault*
Department of Chemistry, McGill University, 3420 University Street, Montreal, QC, H3A 2A7, CanadaFax: (þ1) 514 398-7249; E-mail: [email protected]
Received: November 5, 2003; Revised: December 20, 2003; Accepted: December 22, 2003; DOI: 10.1002/mabi.200300088
Keywords: free radical polymerization; graft copolymers; macromonomers; poly(3-hydroxybutyrate)
Introduction
Polymer chemists have widely used the graft and block
copolymer scaffold to innovate in various domains, like
textiles, tough plastics, or lithography. More recently,
biodegradability and biocompatibility became part of the
working knowledge which enlists polymers into biomedical
applications. Bacterial poly(3-hydroxybutyrate), PHB, as a
biodegradable, biocompatible thermoplastic, slowly hydro-
lyzing in vivo,[1–4] is an interesting starting material for
long-term drug release,[4,5] bone replacement therapy,[6]
fracture treatment,[7] and bone cements.[8–10] The latter
are used to anchor artificial joints (e.g. hips, knees, or
shoulders), by filling the free space between the prosthesis
stem and the bone.[11] They can also be used to rein-
force bones undergoing osteoporosis. Biocompatible bone
cements hold promise for combining permanence and
bone-bonding characteristics.
Poly(methyl methacrylate), PMMA, or PMMA-based
polymers constitute the basic materials of commercial bone
cements, which are prepared by mixing two components
just before the injection into the space between the bone
lumen and the prosthetis stem. One component is a powder:
premade polymer (generally PMMA or a mixture of
PMMA and PMMA-co-polystyrene) particles, a radio-
opacifier (usually barium sulfate), and benzoyl peroxide.
The other component is a liquid: methyl methacrylate
mixed with N,N-dimethyl-p-toluidine, DMPT. When the
two components are mixed, the methyl methacrylate par-
tially dissolves or swells the polymer particles, while
DMPT activates the free-radical initiator benzoyl peroxide
at room temperature to form benzoyl radicals, thereby
initiating the polymerization of methyl methacrylate in the
coalesced polymer particles. Using prepolymerized parti-
cles allows for a considerable reduction of the total heat
generated during the polymerization, and of the shrinkage
of the resulting material. When the mixture starts to thicken
(a matter of minutes), the oily paste is then injected, and a
thick dough forms and progressively hardens in situ.[11]
With its biocompatibility and its rapid processing, this type
of bone cement is widely used.
However, this material presents several drawbacks. For
example, PMMA bone cement presents much weaker
mechanical properties than cortical bone.[12] A long-term
loosening of the cement may also appear, possibly due to
the presence of a fibrous tissue observed at the inter-
face between the bone and the PMMA cement.[12] A
thermal necrosis of the bone cells was also observed, caused
Summary: Graft copolymers of poly(methyl methacrylate)with poly(3-hydroxybutyrate), PHB, segments as long sidechains were prepared by the macromonomer method. PHBmacromonomers were prepared from the esterification ofoligomers with 2-hydroxyethyl methacrylate at their car-boxylic acid end. Esterification products displayed lowpolydispersity indices (ca. 1.2) and a functionality of over83%, with a Mn of 2 020. Using free radical polymerizationmethods, the macromonomers were copolymerized withmethyl methacrylate to yield graft (comb type) copolymers atdifferent comonomer feed ratios. The graft copolymerscontained from 0.5 to 14 mol-% of PHB blocks, with a glasstransition temperature decreasing from 100 to 3 8C.
Synthesis of PMMA-graft-PHB by the copolymerization ofPHB macromonomers with methyl methacrylate.
Macromol. Biosci. 2004, 4, 262–268 DOI: 10.1002/mabi.200300088 � 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
262 Full Paper
by excessive heat generated by the in situ polymeriza-
tion,[8,9,13] the temperature at the cement mantle center
reaching 67 to 124 8C, depending on the cement used.[14]
In addition, the bone can undergo a chemical necrosis due to
unreacted MMA.[13–15] Cracks can also develop, because
of pores in the cement or fatigue at the cement–bone
interface. Pores in the material can occur due to the trapping
of air during the wetting of the powder by the liquid
component, during stirring, injection, or monomer volati-
lization during the in situ polymerization.[15,16]
To overcome these drawbacks, alternatives to the acrylic
bone cement were proposed, with either a modification
of the processing, which is very dependent on the opera-
tor’s technique,[15,16] or the type of monomer and polymer
to be used.[8,9,13] The use of biodegradable materials
has been proposed as alternatives for PMMA powder
component.[8–10,17] The progressive in vivo degradation of
this component leaves channels within the cement,
allowing the growth of bone cells around and in the cement,
and therefore reducing its loosening.[8–10,17] Espigares et al.
reported a bone cement formulation with a polymer
component being a corn starch/cellulose acetate blend with
hydroxyapatite as bioactive ceramic filler.[17] Bunel
et al.[8,9], and Jiang et al.[10] described biocompatible and
partially biodegradable bone cements, including at least a
hydrosoluble or hydrolyzable component. The proposed
systems included a polymer component composed of
a hydrophilic hydrosoluble polymer, for example, poly
((meth)acrylic acid), poly((meth)acrylamide), poly(vinyl
alcohol), poly(vinylpyrrolidone), poly(ethylene oxide),[8,9]
and/or a hydrophobic hydrolyzable polymer, for example,
poly(glycolic acid), poly(lactic acid), PLA, poly(lactone),
poly(hydroxybutyrate), poly(hydroxyvalerate),[8–10] poly
(oxalates), calcium triphosphate, or hydroxyapatite,[8]
poly(dioxanone), poly (trimethylene carbonate), polyan-
hydride.[10]
Previous references to grafting of PHB are scarse.
Yalpani et al. reported the grafting of low-molecular-
weight PHB on chitosan and cellulose acetate by coupling
reactions,[18] while Kowalczuk and co-workers reported the
synthesis of poly(methyl methacrylate)-graft-poly((R,S)-3-
hydroxybutyrate) by anionic grafting of b-butyrolactone on
poly(methyl methacrylate).[19] Such type of material with
isotactic PHB can also be obtained by the copolymerization
of macromonomers of bacterial PHB, with a low-molecu-
lar-weight comonomer of the (meth)acrylic family. To date,
the synthesis of graft copolymers with a (meth)acrylic
main chain and isotactic PHB segments as side chains,
using the macromonomer method, has not been reported. Le
Borgne and co-workers synthesized graft copolymers with
oligomers of PLA, as side chains and a (meth)acrylic
backbone for the controlled release of antifouling agents
for marine paints in seawater.[20,21] Graft copolymers with
an acrylic-type backbone and side chains composed of
segments of PLA, were synthesized by the copolyme-
rization of (meth)acrylic PLA macromonomers with
methyl methacrylate.[22] These workers achieved a struc-
tural control on the incorporation of the macromonomers in
the main chain by the copolymerization of a mixture of
methacrylic and acrylic PLA macromonomers with methyl
methacrylate.[22]
Our approach to a bone cement formulation is to propose
novel copolymers of PMMA with PHB segments as side
chains (Scheme 1) for the polymer component, achieved by
copolymerizing MMA and PHB macromonomers using
free radicals methods. The macromonomers were obtained
by esterification at one end group of PHB oligomers
produced by thermal degradation of bacterial PHB,[23] with
2-hydroxyethyl methacrylate, HEMA. PMMA-graft-PHB
copolymers were studied by DSC and X-ray powder
diffraction.
Experimental Part
Materials
High-molecular-weight bacterial PHB was obtained fromBiomer Inc. (Forst-Karsten-Strasse 15, D-82152, Krailing,Germany), referenced 16M, and used ‘‘as received’’. Thenumber-average molecular weight and polydispersity, mea-sured by GPC, were respectively 108 400 and 2.3. HEMA(Aldrich, 97%) was distilled under reduced pressure and storedat �20 8C. The compound N,N0-dicyclohexylcarbodiimide(DCC, Aldrich, 99%) was dried under vacuum for over 2 days.Methylene chloride (CH2Cl2, Fisher, HPLC grade) was driedover calcium hydride for at least 2 days and quickly filteredjust before use as solvent for the preparation of PHBmacromonomers. MMA (Aldrich, 99%) was stirred overcalcium hydride for 1 h, distilled under reduced pressure, andstored at �20 8C. 2,20-Azoisobutyronitrile (BDH ChemicalsLtd) was recrystallized from methanol. Anisole (Aldrich,anhydrous, 97%) and 4-dimethylaminopyridine, DMAP, wereused ‘‘as received’’. Methanol (Fisher, HPLC grade) andmethylene chloride (Fisher, HPLC grade), used for recoveryand purification of products, were also used without furtherpurification.
Measurements
Gel Permeation Chromatography, GPC, analyses were per-formed at room temperature with chloroform as eluent, at aflow rate of 1 mL �min�1. Two Waters Styragel columns HR3and HR4 connected in series were used, and the detector was aHewlett Packard refractive index HP 1047 RI. Poly(methylmethacrylate) standards were used for calibration. Proton
Scheme 1. Cartoon of graft copolymer of PMMA and PHB.
Synthesis and Properties of Graft Copolymers Based on Poly(3-hydroxybutyrate) Macromonomers 263
Macromol. Biosci. 2004, 4, 262–268 www.mbs-journal.de � 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Nuclear Magnetic Resonance, 1H NMR, experiments werecarried out with a Varian Unity 500 MHz at room temperature.The samples were dissolved in deuterated chloroform CDCl3.The internal standard was tetramethylsilane. X-ray powderdiffraction analyses were performed on a X-ray diffractometerfrom Nicolet XRD Corporation, operated at 40 kVand 25 mA,with a scattering angle Y increasing from 2.5 to 308, byincrements of 0.18, in step duration of 108 sec�1. A copper X-ray anode was used to provide CuKa radiation (l¼ 0.154 nm).Differential Scanning Calorimetry, DSC, experiments wererecorded using a DSC Q1000 calorimeter, equipped with arefrigerated cooling system, from TA Instruments, undernitrogen flow (50 mL �min�1). Indium was used to calibrate theinstrument. The samples were heated from 40 8C to 160 8C,held for 2 min, cooled down to�50 8C, held for 2 min, reheatedto 160 8C, held for 2 min, and finally cooled down to 40 8C. Allheating and cooling ramps were performed at 10 8C �min�1.Glass transition temperatures were obtained at the inflectionpoint on the second heat ramp. Melting points were taken at theminimum value of the melting endotherm, also on the secondheat ramp. Crystallization temperatures were measured duringthe second temperature cycle, at the maximum value of theexotherm.
Preparation of PHB Oligomers
PHB oligomers were prepared by the thermal degradation ofhigh-molecular-weight bacterial polyester at 200 8C for 5 h.[23]
The product was purified by dissolution in methylene chlorideand precipitation in methanol (solvent mixture volume ratio:methylene chloride to methanol: 1:7), then filtered and driedunder vacuum to a constant mass.
Preparation of PHB Macromonomers
The esterification of oligomers of PHB at their carboxylic acidends with HEMA, usedN,N0-dicyclohexylcarbodiimide, DCC,as an activating agent, and a catalytic amount of 4-dimethylaminopyridine, DMAP,[24] in a PHB:HEMA:DCC:D-MAP molar ratio of 1:3:3:0.3, following a method used foroligomers of poly(lactic acid).[20] After addition of DCC to asolution of PHB, HEMA, and DMAP in anhydrous (dried overCaH2) methylene chloride at 0 8C, the reaction medium waskept at room temperature for 6 days. After removal of thedicyclohexyl urea by-product by filtration, the product wasrecovered by precipitation in methanol (solvent mixturevolume ratio: methylene chloride to methanol: 1:7) and driedunder vacuum to a constant mass.
Preparation of PMMA-graft-PHB
PHB macromonomers (0.384 g, 0.190 mmol), MMA (2.16 g,21.6 mmol) (comonomer feed ratio: 0.9:99.1, mol-%) wereplaced in a round bottom flask, and the suspension was purgedwith argon for at least 30 min. AIBN (0.0155 g, 0.0944 mmol)was charged in a vial with a cap equipped with a septum andpurged with argon for at least 30 min. Anisole (4 mL) was thentransferred under argon to the vial containing the AIBN, whichwas stirred until complete dissolution, and purged with argon
for 10 min. This solution was transferred under argon to thereaction flask, which was then placed in a 70� 1 8C heatedsilicone oil bath. The reaction was stopped after 45 h. Thereaction medium was transferred to an Erlenmeyer flask,and methanol (reaction medium/methanol: 1:10) was addeddropwise under magnetic stirring. The obtained suspensionwas filtered, and the solid product was dried under vacuum to aconstant mass. The product was then purified by dissolution inmethylene chloride and precipitation in methanol, followed byfiltration and vacuum drying.
Copolymerizations with PHB macromonomers to MMAmolar feed ratios of 3, 5, 7, 10 mol-%, and homopolymeriza-tions of MMA in anisole were carried out using this procedure,with an initial concentration of PHB macromonomers of0.1 g �mL�1 of anisole.
Results and Discussion
Graft Copolymers Based on PHB Macromonomers
The thermal instability of high-molecular-weight PHB is a
fundamental molecular property, which enables molecular
cracking, in the petrochemical feedstock tradition, initiated
by the ‘‘McLafferty rearrangement’’.[23,25–27] Absolute
number-average molecular weights, Mn, were obtained by1H NMR spectroscopy, using the average ratio of the peak
areas of the repeat unit protons to the ones of the crotonate
end groups. The crude oligomers were found to have an
absolute Mn of 730, whereas the purified ones had an
absoluteMn of 1 800. Polydispersity indices of the samples,
PDI, measured by GPC, decreased from about 2.7 for the
crude product to 1.9 after purification.
For conversion to macromonomers, the PHB oligomers
were esterified at their carboxylic acid ends with HEMA
(Scheme 2). The precipitation step for product recovery
induced a fractionation of the PHB macromolecules. GPC
analyses showed a sample polydispersity decreased to
approximately 1.2, and the relative Mn value increased to
2 500, whereas the absolute Mn value, obtained by NMR
spectroscopy on the same sample, was calculated at 2 020.
The fractionation also lowered the reaction yields to 83%,
due to the solubility of very low-molecular-weight PHB in
the solvent mixture of methylene chloride and methanol.
The structure of the macromonomers was determined
by 1H NMR spectroscopy in deuterated chloroform. The
products were found to contain two unsaturated end groups:
Scheme 2. Synthesis of PHB macromonomers by oligomeresterification using 2-hydroxyethyl methacrylate, with N,N0-dicyclohexylcarbodiimide, DCC, and 4-dimethylaminopyridine,DMAP, in anhydrous methylene chloride.
264 S. Nguyen, R. H. Marchessault
Macromol. Biosci. 2004, 4, 262–268 www.mbs-journal.de � 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
one of crotonate-type, as in the original oligomers, and the
other one of methacrylate-type. The 1H NMR spectrum of
the product (PHB macromonomer) end groups is shown on
Figure 1. On Figure 1(i), the multiplet peaks (doublets of
quadruplets) at approximately 6.9 and 6.3 ppm correspond
to the protons a and a0 of the crotonate end CH3–CH CH–
C(O)O, respectively in the trans and cis configuration of the
double bond. The doublet peaks at approximately 5.8 and
5.7 ppm represent the protons b and b0 of the crotonate
end CH3–CH CH–C(O)O, also respectively for the trans
and cis configuration. The trans/cis ratio of this double bond
was calculated using the peak integrals corresponding to
the protons in the trans configuration and the one in the cis
configuration and amounted to 95:5, which is similar to the
one for the oligomers, 95:5. The protons g and d of the
methacrylate end CH2 C(CH3)–C(O)O–(CH2)2–O(O)C
appear at approximately 6.1 and approximately 5.6 ppm.
Figure 1(ii) represents the 1H NMR spectrum between
3.7 and 4.4 ppm for HEMA and the esterification product
on traces A and B respectively. The triplet peaks z and
Z correspond respectively to the methylene protons
CH2 C(CH3)–C(O)O–CH2–CH2–OH and CH2 C(CH3)–
C(O)O–CH2–CH2–OH. The singlet peak at 4.3 ppm on
trace B corresponds to the four equivalent protons e at
the same end CH2 C(CH3)–C(O)O–(CH2)2–O(O)C, sur-
rounded by two ester groups. The existence of this peak,
integral of which is approximately four times that of peaks gand d, as well as the disappearance of the triplet peaks z and
Z, confirmed the synthesis of PHB methacrylic macro-
monomers. The functionality of the products, F, calculated
as the integral ratio of the peaks of the methacrylate end
protons to the ones of the crotonate end, was found to
be 83%.
DSC melting endotherms of the PHB macromonomers
gave two sharp peaks: at 120 8C and 132 8C, the second one
being the major one. A very sharp crystallization exotherm
was observed on the cooling ramps, at 94 8C. This high
crystallinity was confirmed by X-ray diffraction, with a
powder pattern characteristic of bacterial PHB (Figure 2).[28]
Graft copolymers of PMMA and PHB were prepared
by the macromonomer method using free radical polymer-
ization techniques, at different comonomer feed ratios
(Scheme 3).
Results are shown in Table 1. Mn and F for the PHB
macromonomers (PHB* in Table 1) used are given for each
entry, and calculated from 1H NMR analyses. Their final
conversions were obtained from the 1H NMR spectra of the
copolymers before purification, as at least a portion of
free PHB macromonomers was removed from this step. The
calculation of the conversions CPHB* was derived from the
integral ratio of the peaks of the methacrylate end protons to
the ones of the crotonate end, taking into account the
macromonomer functionality (Equation 1).
CPHB*ð%Þ ¼ 1 � Amethacrylate
Acrotonate � F
� �� �� 100 ð1Þ
Amethacrylate: average peak area for one methacrylate proton,
Acrotonate: average peak area for one crotonate proton, F:
functionality of PHB macromonomers.
Figure 1. 1H NMR spectrum (500 MHz, CDCl3) of PHBmacromonomer. (i) Peaks for the protons of the unsaturated endgroups; (ii) A: methylene protons z and Z of 2-hydroxyethylmethacrylate; B: methylene protons e of the methacrylic endgroups of the PHB macromonomers. NMR conditions: deuteratedchloroform as solvent, tetramethylsilane as internal standard,room temperature.
Figure 2. X-ray powder diffraction patterns of PHB macro-monomer (top curve), and PMMA-graft-39 wt.-% PHB (bottomcurve). Both samples were precipitated from solution as crystal-line powders.
Synthesis and Properties of Graft Copolymers Based on Poly(3-hydroxybutyrate) Macromonomers 265
Macromol. Biosci. 2004, 4, 262–268 www.mbs-journal.de � 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
The PHB macromonomer molar content in the copoly-
mers XPHB*,mol was obtained from the 1H NMR analyses of
the purified copolymers, by the ratio of the average peak
integral corresponding to the macromonomer units, to the
sum of peak integrals of the protons of both comonomers
(Equation 2).
XPHB*;mol ¼APHB*
APHB*þAMMA
� �� 100
APHB* ¼ AHB
nHB
� �� F � CPHB*
ð2Þ
APHB*: average peak area for one methacrylate proton,
AMMA: peak area for one proton of the O–CH3 group in the
methyl methacrylate units, nHB: number of 3-hydroxybu-
rate units in PHB macromonomers.
The average peak area corresponding to the macro-
monomer units was calculated from the peak integrals of the
repeat units (protons of the methyne and methylene groups)
of the PHB macromonomer and the degree of polymeriza-
tion of the macromonomer, taking the macromonomer
functionality and its conversion into account. The number-
average degrees of polymerizations or average number of
repeat units of the comonomers, respectively DPMMA and
DPPHB* for methyl methacrylate and PHB macromono-
mers, and their weight ratio in the purified copolymers were
obtained from both 1H NMR spectroscopy and GPC. They
were given here as indications, as the molar masses from
GPC are relative values to the PMMA standard polymers
used for calibration. Increasing the PHB macromonomers
content in the copolymerization feed seems to hinder
or slow the polymerization of both comonomers, as the
conversion of the PHB macromonomers decreased, as well
as DPMMA, DPPHB*. All polydispersity indices of the
copolymers were below 2. The presence of free PHB
macromonomers in the products after purification was
evidenced by 1H NMR spectroscopy and GPC at PHB
macromonomers contents at 68 and 78 wt.-% in the co-
polymers. In these copolymers, the extraction of the free
PHB macromonomers has not been successful so far.
Properties of PMMA-graft-PHB
Figure 2 shows crystalline X-ray diffraction peaks of PHB
for graft copolymers with 39 wt.-% PHB. The crystal-
lization properties were also observed on the DSC melting
endotherms of the copolymers, shown in Figure 3. A
copolymer melting endotherm, well defined but with a
major peak followed by a broad shoulder, was observed on
the first heating ramp. Up to 41 wt.-% of PHB content in the
copolymers, the main melting peak was significantly lower
than the one for the macromonomer itself: 99 to 109 8C, and
no melting endotherm was observed on the second heating
ramp, indicating restricted nucleation and absence of
Scheme 3. Synthesis of PMMA-graft-PHB by the copolymer-ization of PHB macromonomers with methyl methacrylate.
Table 1. Synthesis of PMMA-graft-PHB copolymers by free radicals polymerization method. PHB*: PHB macromonomers.
No. Feed RatioMMA:PHB*
Comonomer PHB* Copolymerc) (after purification)
mol-% (wt.-%)a) Mn
(NMR)F Conversion DPMMA=DPPHB*
d) Mn
(GPC)PDI
(GPC)MMA:PHB*
[%] (NMR) [%] (NMRb)) mol-% (wt.-%)a)
1 100:0 (100:0) – – – 720/0 72 200 1.5 100:0 (100:0)2 100:0 (100:0) – – – 810/0 80 800 1.4 100:0 (100:0)3 99.13:0.87 (85:15) 2 020 83 100 7 170/36 72 700 1.3 99.50:0.50 (91:9)4 99.07:0.93 (84:16) 2 020 83 100 4 060/44 89 300 1.5 98.9:1.1 (82:18)5 97.3:2.7 (66:34) 1 810 90 100 1 760/37 66 800 1.6 97.9:2.1 (72:28)6 95.2:4.8 (52:48) 1 810 90 99 980/34 62 300 1.6 96.6:3.4 (61:39)7 93.1:6.9 (38:62) 2 220 83 93 160/15 33 800 1.8 91.1:8.9 (32:68)8 90.6:9.4 (32:68) 2 020 100 71 160/18 37 300 1.8 90:10 (31:69)9 90.3:9.7 (30:70) 2 220 83 84 82/13 29 600 1.6 86.1:13.9 (22:78)
a) MMA:PHB* means molar fraction in % of monomer MMA: molar fraction in % of macromonomer PHB*; the values given in bracketsare weight fractions in %.
b) Calculated from the NMR spectrum on the copolymer before purification.c) The polymerization were performed in anisole at 70 8C, for 45 h, with [MMA]0:[AIBN]¼ 200:1.d) DP: number-average degree of polymerization.
266 S. Nguyen, R. H. Marchessault
Macromol. Biosci. 2004, 4, 262–268 www.mbs-journal.de � 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
crystallinity. Between 68 and 78 wt.-% of PHB content, on
the first heat ramp, the melting endotherm was at 113–
115 8C; on the second heat ramp, a broad crystallization
exotherm was followed by a melting endotherm at 132–
139 8C. These Tm values were close the ones of PHB
macromonomers, which can be attributed to an increased
proportion of PHB segments in the copolymers, as well as
some contribution of free PHB macromonomers in the case
of the copolymers containing 68 and 78 wt.-% of PHB. We
can conclude that the graft copolymers are composed of
small PHB crystallites embedded in a PMMA noncrystal-
line matrix. As polymer particles in bone cements, the graft
copolymers would retain the same physical state, provided
that during the cement processing, methyl methacrylate
does not preferentially swell PHB.
One drawback of PMMA bone cements is their brittle-
ness at body temperature.[11,29] Kuhn reported the glass
transition temperatures of commercial bone cements,[11]
the values of which ranged between 70 and 100 8C for dry
samples, and 60 and 70 8C for samples stored in water at
37 8C. A minimum glass transition temperature (Tg), dis-
tinctly above body temperature was specified to minimize
the risk of prosthesis sinking due to creep.[11] To control
brittleness of the PMMA bone cements, one approach used
a formulation with the usual components, but combined to
a powder composed of a polymer or copolymer with a Tg
below body temperature, such as poly(butyl methacry-
late),[14,29,30] or more generally homopolymers or copoly-
mers of polyacrylates and/or polymethacrylates with such
Tg values.[31] The resulting bone cement was viscoelastic,
with rubbery particles dispersed in a brittle matrix,[14,29,30]
creating a tough material.
The PMMA-graft-PHB copolymers of this study dis-
played a single Tg, measured by DSC, which decreased
regularly with increasing macromonomer content, as
shown in Figure 4. At 39 wt.-% of PHB, the Tg of the graft
copolymers was recorded at around body temperature,
which suggests that this is the composition range to be
further investigated for this type of bone cement, since at
higher PHB content the cement might undergo creep. At
this stage of our investigation, the influence of PHB
crystallinity on mechanical properties is unknown.
Conclusion
The first description of PHB methacrylic macromonomers
synthesis and copolymerization gives promise of new
biomaterials properties. The single glass transitions observ-
ed for each copolymer composition suggested a random
arrangement of the residues and that macrodomains were
nanosized. The PHB grafts should be divided between small
crystallites, which yielded the observed X-ray diffraction
maxima, and blended with PMMA segments to form non-
crystalline regions, responsible for the observed glass
transitions. Using DSC melting endotherms, a gradual
increase of crystallinity was observed with increasing PHB
macromonomer content. We can conclude that the micro-
texture of the copolymers is relatively uniform, and the
resistance to strain will depend on both noncrystalline and
crystalline domains. The latter can act as bridges between
chains, imparting continuity and pseudo-crosslinking to the
overall structure.
These comb polymers, while still undergoing quantita-
tive testing, are expected to be susceptible to slow weight
loss due to biodegradation and hydrolytic erosion of the
PHB side chains; in both cases, the vinyl backbone should
retain its integrity. PHB graft copolymers should also offer
an improved level of biocompatibility. More generally, the
rich family of potential macromonomers available from the
microbial world,[32] that is, poly(hydroxyalkanoate)s,
Figure 3. DSC thermograms of PHB macromonomer andPMMA-graft-PHB copolymers: second heating ramps for copo-lymers with 41 wt.-% PHB (trace A), 68 wt.-% PHB (trace B),69 wt.-% PHB (trace C), 78 wt.-% PHB (trace D), and PHBmacromonomer (trace E).
Figure 4. Evolution of the glass transition temperature of thepolymers (after purification), obtained from DSC experiments,with the PHB macromonomer weight content in the polymer.
Synthesis and Properties of Graft Copolymers Based on Poly(3-hydroxybutyrate) Macromonomers 267
Macromol. Biosci. 2004, 4, 262–268 www.mbs-journal.de � 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
should offer a range of mechanical and surface character-
istics for implant and bone cement applications.
Acknowledgement: We thank the Industrial Materials Instituteof the National Research Council of Canada, Boucherville, QC,Canada, for the use of the Brabender apparatus used for the largescale thermal degradation of poly(3-hydroxybutyrate). Specialthanks are addressed to Drs. Hung Anh Nguyen, Alain Le Borgne,and Prof. Philippe Guerin of the Laboratoire de Recherche sur lesPolymeres (CNRS, UMR C7581), Thiais, France. The NaturalSciences and Engineering Research Council and Labopharm Inc.provided financial support.
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