Applied Surface Science 258 (2012) 6823–6830
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Applied Surface Science
journal homepage: www.elsevier.com/locate/apsusc
Hydroxyapatite–poly(l-lactide) nanohybrids via surface-initiated ATRP for
improving bone-like apatite-formation abilities
Jiqing He, Xiaoping Yang, Jiaofu Mao, Fujian Xu, Qing Cai ∗
State Key Laboratory of Organic-Inorganic Composites, Key Laboratory of Carbon Fiber and Functional Polymers, Ministry of Education, College of Materials Science & Engineering,
Beijing University of Chemical Technology, Beijing 100029, China
a r t i c l e
i n f o
Article history:
Received 7 January 2012
Received in revised form 18 March 2012
Accepted 19 March 2012
Available online 7 April 2012
Keywords:
Hydroxyapatite
PLLA
Nanohybrids
ATRP
Biomineralization
a b s t r a c t
It is important to improve the compatibility of hydroxyapatite (HA) nanoparticles in biodegradable
polyesters to obtain desirable nanocomposites for bone tissue engineering applications. Polymer grafting has been proven an efficient way to get nanohybrids with good dispersibility in polymeric matrixes.
In this paper, a new strategy to prepare HA–poly(l-lactide) (PLLA) nanohybrids was developed, where
PLLA oligomers were grafted from HA nanoparticle surfaces via surface-initiated atom transfer radical
polymerization (ATRP) of methylacrylate group terminated PLLA macromonomers (PLLA-MA). HA with
the derived ATRP initiators was obtained by (1) preparation of HA from precursors in the presence of 3aminopropyl-triethoxysilane (APTS) to produce the HA surface with terminal NH2 groups (HA–NH2 ) and
(2) reaction of the NH2 groups of the HA–NH2 nanoparticles with 2-bromoisobutyryl bromide (BIBB) to
produce the 2-bromoisobutyryl-immobilized nanoparticles (HA–Br). The obtained HA–PLLA nanohybrids
demonstrated good dispersibility in chloroform. With the good dispersion of HA–PLLA nanohybrids in
PLLA matrix, the resultant PLLA/HA–PLLA nanocomposites could much faster induce bone-like apatiteformation in simulated body fluids (SBF) than the PLLA/HA counterparts where the HA nanoparticles
aggregated heavily. With the versatility of ATRP, properly, grafting oligomeric PLLA chains from HA
nanoparticle surfaces is an effective means for the design of novel HA–polymer biohybrids for future
bone tissue engineering applications.
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
Due to its high bioactivity, biocompatibility and osteoconductivity, apatite, especially hydroxyapatite (HA) called as bioceramic,
is widely used as inorganic nanomaterial fillers in polymeric
matrixes for bone-like artificial ceramic/polymer composites [1–6].
Biodegradable aliphatic polyesters, especially those lactide-based
ones, are the most remarkable matrixes for making biomedical
composites. They are commercially available, easily processed and
proven biocompatible [7–10]. However, due to the desirable properties of nanoscale fillers such as high surface energy, as well as the
significant incompatibility features between inorganic nanoparticles and polymeric matrix, the entrapped HA nanoparticles in the
polyester matrixes would intend to aggregate even at low contents.
The lack of good interfacial adhesion between HA and polymer
matrix usually gives rise to inferior nanocomposites [11,12]. It
was reported that poly(l-lactide) (PLLA) oligomers could grafted
covalently onto the surfaces of HA nanoparticles, either by condensation reactions between the hydroxyls on HA and the carbonyl end
∗ Corresponding author. Tel.: +86 10 64412084; fax: +86 10 64412084.
E-mail address: caiqing@mail.buct.edu.cn (Q. Cai).
0169-4332/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.apsusc.2012.03.109
groups of PLLA [13], or directly ring-opening polymerization of llactide initiated by the hydroxyls of HA [14]. Such strategies could
largely improve the dispersion of HA nanoparticles in PLLA matrix.
Recent progresses in controlled radical polymerizations, particularly in atom transfer radical polymerization (ATRP), have
provided a unique means for the design and synthesis of functional
biomaterials [15–18]. Surface-initiated ATRP opens a new strategy for the surface modification of nanoparticles including silicon
[19–21], iron dioxide [22,23], and HA [24–26]. Lang et al. grafted
poly(methyl methacrylate) onto HA particles by surface-initiated
ATRP of methyl methacrylate directly from HA particles [24]. By
combination of ATRP and ring-opening polymerization, Zeng et al.
reported a kind of comb-shaped poly(␧-caprolactone) brushes on
the surface of HA nanoparticles where the hydroxyl groups in ATRPgrafted poly(2-hydroxyethyl methacrylate) (PHEMA) on HA surface
were used to initiate the ROP of ␧-caprolactone [25]. But the poor
solubility or dispersibility of PHEMA-grafted HA particles in lactone
monomers, either liquid ␧-CL or molten lactide in bulk ROP, would
seriously affect the reaction efficiency and reproducibility.
In this work, a new approach to construct well-defined HA–PLLA
nanohybrids by surface-initiated ATRP was reported (Fig. 1). The
methylacrylate-terminated PLLA (PLLA-MA) was first prepared by
reacting hydroxyl-ended PLLA with methacrylic anhydride. Then,
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J. He et al. / Applied Surface Science 258 (2012) 6823–6830
Fig. 1. Schematic diagram illustrating the surface-initiated ATRP of methylacrylate group-terminated PLLA (PLLA-MA) from the HA–Br surface to produce the HA–PLLA
nanohybrids for improving bone-like apatite-formation abilities.
the PLLA brushes were obtained from the HA nanoparticles via
ATRP of PLLA-MA. The HA–PLLA nanohybrids were characterized by X-ray photoelectron spectroscopy (XPS), wide angle X-ray
diffraction (WXRD), Fourier transform infra-red spectroscopy (FTIR) and thermal gravimetric analysis (TGA). The size distribution
and dispersibility of the HA–PLLA nanohybrids were compared
with the pristine HA. The nanocomposites composed of HA–PLLA
nanohybrids and PLLA matrix were subsequently assessed by
biomineralization test with simulated body fluids (SBF) for identifying the effect of HA dispersion on bone-like apatite formation.
2. Experimental
2.1. Materials
Calcium nitrate tetrahydrate [Ca(NO3 )2 ·4H2 O], diammonium
hydrogen phosphate [(NH4 )2 HPO4 ], and ammonium hydroxide (NH3 ·H2 O, 25%), triethylamine, methylene dichloride, ethyl
acetate, dioxane, dimethyl sulfoxide (DMSO, 99%), 3-aminopropyltriethoxysilane (APTS, 98%), 2-bromoisobutyrate bromide (BIBB,
97%), 1,1,4,7,7-pentamethyldiethylenetriamine (PMDETA, 97%),
copper (I) bromide (CuBr, 98%) and pristine HA (30 nm in width,
100 nm in length) were obtained from Aldrich Chemical Co., Ltd. lLactide was purchased from Purac (Netherlands) and recrystallized
in anhydrous ethyl acetate before use. PLLAs were synthesized in
our lab, and their number average of the molecular weights (Mn )
were ∼3000 for ATRP grafting and ∼105 for composite matrix.
2.2. Synthesis of hydroxyapatite initiator
The immobilization of the ATRP initiators on HA nanoparticles was carried out in two steps (Fig. 1): (1) preparation of HA
from precursors in the presence of APTS [9,24,26,27] to produce
the HA surfaces with terminal NH2 groups (HA–NH2 ) and (2)
reaction of the NH2 groups of the HA–NH2 nanoparticles with
BIBB to produce the 2-bromoisobutyryl-immobilized nanoparticles
(HA–Br) for the subsequent surface-initiated ATRP. Briefly, 50 mL
of 0.1 M Ca(NO3 )2 ·4H2 O aqueous solution was adjusted to pH 10
with NH3 ·H2 O, the solution was heated to 90 ◦ C, and then 50 mL of
0.06 M (NH4 )2 HPO4 at pH 10 (adjusted with NH3 ·H2 O) was added
dropwise under stirring. Subsequently, APTS (2.5 mL) solution in
50 mL distilled water was added to the system. The pH of the system was adjusted to 9–10 with NH3 ·H2 O again, and the reaction
was continued at 90 ◦ C for 3 h. Then, the suspension was centrifuged
at 4000 rpm for 10 min and the precipitants were washed repeatedly with distilled water. After centrifuged, the powder was dried
naturally at room temperature followed by cured at 130 ◦ C for 2 h
to strengthen the silane coating upon formation of a polysiloxane
network structure, giving rise to HA–NH2 . For the reaction of NH2
groups of HA–NH2 with BIBB, 5 g of HA–NH2 was introduced into
a 100 mL flask containing 40 mL of dichloromethane and 1.5 mL of
triethylamine, followed by sonication for 30 min and addition of
10 mL of dichloromethane containing 3 mL of BIBB. The reaction
mixture was gently stirred for 2 h at 0 ◦ C and then for 24 h at room
temperature to produce HA–Br. HA–Br was washed exhaustively
with copious amounts of deionized water, prior to lyophilization.
The final yield of HA–Br was about 80%.
2.3. Surface-initiated ATRP of PLLA-MA
Methylacrylate group-terminated PLLA (PLLA-MA, Mn = 3000)
was synthesized to produce the macromonomers for ATRP. Briefly,
mono-hydroxyl-ended PLLA (PLLA-OH) was firstly synthesized
from ROP of l-lactide initiated by hexadecanol at 140 ◦ C for 24 h.
The hydroxyl group was then reacted with methacrylic anhydride
in the presence of triethylamine in dried dichloromethane to yield
PLLA-MA [28]. In order to obtain PLLA brushes on the HA surface, HA–Br (200 mg), PLLA-MA (0.5 g), and PMDETA (69 ␮L) were
added to 10 mL of mixed solvent of dimethyl sulfone (DMSO) and
dioxane (v:v = 1:4). The reaction mixture was stirred overnight and
then degassed with argon for 10 min. After the CuBr (27 mg) was
introduced into the reaction mixture, the reaction was maintained
at 37 ◦ C for 12 h. At the end of the reaction, the suspension was
retrieved by centrifugation. The products were washed thoroughly
with an excess amount of dioxane twice to remove any residual
unreacted PLLA-MA oligomers, and with methanol twice to remove
J. He et al. / Applied Surface Science 258 (2012) 6823–6830
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Fig. 2. 1 H NMR spectra of (a) monohydroxyl-terminated PLLA (PLLA-OH) and (b) methylacrylate group-terminated PLLA (PLLA-MA).
catalyst. HA–PLLA nanohybrids were vacuum-dried at room temperature until constant weight for further use.
2.4. Characterization of HA–PLLA nanohybrids
The chemical compositions of the modified HA surfaces were
determined by XPS. The XPS measurements were performed on a
Kratos AXIS HSi spectrometer using a monochromatized Al K␣ Xray source (1486.6 eV photons). The WAXD data from 10◦ to 90◦
of the samples were measured using a UItimaIII X-Ray Diffractometer with a Cu tube anode (2500VB2+/PC, 40 kV, 200 mA). FT-IR
was recorded on a Nicolet 8700 spectrometer, where samples were
milled with potassium bromide powders and pressed into transparent tablets. The surface area of HA particles was determined by N2
gas adsorption on an ASAP2020M System. Prior to measurement,
the sample was degassed at 200 ◦ C for 24 h. Specific surface area
was calculated using the Brunauer–Emmett–Teller (BET) equation.
The amount of grafted PLLA on HA was determined by TGA using a
Q50 thermogravimetric analyzer (TA instruments, Delaware, USA).
The TGA measurements were carried out in air from room temperature to 800 ◦ C at a heating rate of 20 ◦ C/min. Scanning electron
microscopy images were inspected by a FESEM (Hitachi S-4700,
Japan) at an accelerating voltage of 5 kV. Before observation, the
samples were sputter-coated with a thin layer of platinum under
the metallization conditions of 2 mA and 0.001 Pa to allow for better
electrical conduction (Polaron E5600, USA).
For TEM observation, HA or modified HA nanoparticles were
dispersed in chloroform for 24 h, dropped onto 400-mesh copper
grids and observed on a Hitachi 800 TEM. Dynamic light scattering
(DLS) was carried out using a BI-90Plus (Brookhaven, USA) with
an 35 mW solid laser to measure the sizes of different samples dispersed in chloroform. Viscosities and refractive index of chloroform
was 0.563 (25 ◦ C) and 1.4476.
2.5. Preparation of PLLA/HA composites
For the control PLLA/HA composites, pre-weighed commercial
HA nanoparticles were dispersed in 20-fold (in weight) chloroform with the help of magnetic stirring and ultrasonic treatment
(ultrasonic power, 500 W, 1 min). For the PLLA/HA–PLLA composites, the prepared HA–PLLA powders were dissolved in 20-fold
chloroform under continuous stirring for 24 h. Then either of the
above HA-containing suspensions was added into chloroform solution containing 0.1 mg/mL of PLLA to achieve the HA contents up to
10 or 30% (wt/wt) in the final composites. The solutions were cast
onto glass plates, solvent evaporated at room temperature for 48 h
and then vacuum-drying at 37 ◦ C was used to remove any residual
solvent. The pure PLLA film was made using the similar way for
comparison.
2.6. Biomineralization study of PLLA/HA composites
In this work, a modified formulation of the proposed 1.5 SBF
by Zhang et al. [29] was used. The reagent grade NaCl, NaHCO3 ,
KCl, K2 HPO4 ·3H2 O, MgCl2 ·6H2 O, CaCl2 , and Na2 SO4 were dissolved
in distilled water. The ion concentrations in SBF were 1.5 times
to those of human blood plasma. The solution was buffered at
physiological pH 7.4 with Tris and hydrochloric acid (HCl). Composite specimens were soaked in the 1.5 SBF at 37 ◦ C for 1, 2, and
3 days. The SBF was replaced by fresh one every day. At predetermined points, the samples were taken out from the solutions,
gently rinsed with distilled water and freeze-dried. SEM images
were inspected by FESEM. Energy dispersive X-ray spectroscopy
(EDX, GENESIS 307, USA) was obtained without gold coating to
determine the chemical compositions of the apatite depositions.
Randomly selected areas of about 1 mm × 1 mm on the surfaces
from different incubation conditions were examined.
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J. He et al. / Applied Surface Science 258 (2012) 6823–6830
Fig. 3. SEM images of (a) HA–NH2 and (b) HA–Br and XPS spectra of (c) HA–NH2 and (d) HA–Br. The insets show the signals of N1s and Br3d.
3. Results and discussion
3.1. Preparation of methylacrylate-terminated PLLA (PLLA-MA)
The structure of the synthesized PLLA oligomer and its molecular weight could be derived from 1 H NMR spectra (Fig. 2). In addition
to the peaks corresponding to methyl (1.6 ppm) and methylidyne
(5.2 ppm) protons for the hydroxyl terminated PLLA (PLLA-OH), the
peak around 4.3 ppm could be clearly detected, which was contributed to the methylidyne proton adjacent to the end hydroxyl
groups. Based on the integrated area of peaks at 4.3 ppm and
5.2 ppm, the Mn of PLLA-OH was determined ∼3400. After the reaction with methacrylic anhydride, the peak at 4.3 ppm disappeared.
Instead, a group of peaks were detected at 5.6 ppm and 6.2 ppm.
These were related to the unsaturated bond of MA. Based on the
1 H NMR of PLLA-MA, its Mn remained ∼3400, indicating that the
preparation process of PLLA-MA did not destroy the PLLA main
chain.
3.2. Preparation of HA–PLLA nanohybrids
In general, HA particles derivatized with ATRP initiators were
usually prepared by coating APTS onto pre-obtained HA particles
surface and then the NH2 groups of the immobilized APTS were
reacted with BIBB to produce the 2-bromoisobutyryl-immobilized
nanoparticles for the following ATRP. For this procedure, the HA
particles have to be redispersed in solvent by ultrasonic and aggregation was unavoidable. In this study, APTS was added into the
calcium and phosphorous precursor solutions directly, and it could
be attached onto the freshly formed HA particles in wet state. Such
immobilization process would result in uniformly distributed APTS
coating. The prepared HA–NH2 particles were rod like with 150 nm
in length and 10 nm in width (Fig. 3a), and no changes in crystalline structure in comparison with commercial HA nanoparticles
were observed from the XRD data (Fig. 4a and b). The characteristic diffractions of (0 0 2), (1 0 2), (2 1 1), (3 0 0), (2 0 2), (3 1 0), (2 2 2),
(2 1 3) and (4 1 1) crystal faces of HA were clearly identified. In the
FT-IR spectra (Fig. 5a and b), the absorption bands of HA–NH2 also
resembled those of commercial HA. To identify the coating of APTS
component on lab-prepared HA nanoparticles, XPS and TGA analysis were applied. The corresponding strong N1s signal at the BE of
about 399 eV, attributable to the amine ( NH2 ) species, is shown
in Fig. 3c. The TGA data (Fig. 6a and b) demonstrated a 5.8% weight
loss for HA–NH2 compared to the 3.6% weight loss for commercial
HA, due to the decomposition of organic groups on the HA surface.
Fig. 4. XRD patterns of (a) commercial HA, (b) HA–NH2 , (c) HA–Br, and (d) HA–PLLA.
Thus, it was calculated the amount of APTS on HA–NH2 was about
2.2% by weight.
The NH2 groups of the HA–NH2 were then used to be reacted
with BIBB to produce HA–Br for the subsequent surface-initiated
ATRP. The strong Br3d signal at BE of about 69 eV confirmed that
the alkyl halide group has been successfully introduced onto the
HA surface (Fig. 3d) and this process had no effect on HA crystal structure as illustrated by SEM (Fig. 3b), XRD (Fig. 4c) and
Fig. 5. FT-IR spectra of (a) commercial HA, (b) HA–NH2 , (c) HA–Br, and (d) HA–PLLA.
J. He et al. / Applied Surface Science 258 (2012) 6823–6830
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Fig. 6. TGA analysis of (a) commercial HA, (b) HA–NH2 , (c) HA–Br, (d) controlled
HA–Br (treated in DMSO/dioxane mixed solvent at 37 ◦ C for 12 h without addition
of PLLA oligomers) and (e) HA–PLLA.
FT-IR (Fig. 5c) analysis. With the addition of isobutyrate bromide
groups, the weight loss of HA–Br increased to 6.7% (Fig. 6c). The
immobilized amount of bromide groups of HA–Br was determined
0.6%. Based on the above weight loss difference and the 57.48 m2 /g
surface area of HA determined by the BET method, the surface
density of ATRP initiator of HA–Br was estimated to be about
∼0.9 initiators/nm2 .
Using HA–Br ATRP initiators, surface-initiated ATRP of PLLA-MA
oligomers was carried out to produce the HA–PLLA nanohybrids
which were confirmed by FT-IR and TGA analysis. Compared to
other FT-IR profiles, new adsorption peaks around 1730 cm−1 and
3000–2850 cm−1 had been detected for HA–PLLA (Fig. 5d). The former peak related to the C O stretching vibration of ester bond,
and the latter one corresponded to stretching vibrations of alkyl
groups. Fig. 6e demonstrates a weight loss of 7.5% of HA–PLLA.
Based on the 6.7% weight loss of HA–Br, the amount of grafted PLLA
oligomers was very low, only 0.8 wt%. With the initiator density
(0.9 initiators/nm2 ) of the HA nanoparticles and the averaged Mn
(3400 g/mole) of PLLA, the theoretical amount of grafted PLLA could
at least reach 29 wt% if all the bromide groups could initiate one
PLLA-MA oligomer. Since an ionic pathway (SN 2 reaction) to halogen exchange in ATRP had been reported [30], it could be envisioned
that the steric hindrance was a major reason for the low grafting efficiency. Other factors such as low reactivity of methacrylate
groups on chain ends and initiation efficiency of bromide groups
on HA particles, could also reduce the grafted PLLA amount. In this
study, however, it was found that the weight loss of HA–Br had
decreased to 4.8% if it were undergone the same reaction process
in the absence of PLLA-MA oligomers (Fig. 6d). Compared to the initial 6.7% weight loss of freshly obtained HA–Br, this lowered weight
loss revealed that a part of bromide groups had been cleaved from
the HA particles during the PLLA grafting procedure. Therefore, the
amount of grafting PLLA on final products was estimated to be 2.7%
by comparing the weight loss of HA–PLLA (7.5%) and treated HA–Br
(4.8%).
3.3. Characterization of dispersibility of HA nanohybrids
After being stirred for 24 h in chloroform at room temperature,
all HA–NH2 , HA–Br and HA–PLLA could disperse and suspend in the
solvent (Fig. 7a and b). However, HA–NH2 and HA–Br started to be
aggregated and precipitated immediately once the stir was stopped
(Fig. 7c). In the case of HA–PLLA nanohybrids, the suspension
remained quite stable up to several hours, due to the interaction
of the swollen PLLA brushes and the solvent. Dilute chloroform
Fig. 7. Dispersion assay of different samples in CHCl3 solution (0.1%, mg/mL): (a)
initial, (b) after being stirred for 24 h, (c) 1 h after the stir was stopped.
solutions containing freshly dispersed HA–NH2 , HA–Br or HA–PLLA
particles were then subjected to TEM observation and particle size
measurement. Fig. 8a clearly shows the micro-scaled aggregations
of HA–NH2 nanoparticles. With the introduction of isobutyrate bromide groups, the dispersibility of HA–Br was ameliorated owing to
the increasing interaction between isobutyrate bromide groups and
solvent (Fig. 8b). HA–PLLA nanohybrids had the best dispersibility
as illustrated in Fig. 8c. This significantly improved dispersibility
was obviously attributed to the grafted PLLA brushes. Along with
this trend in particle dispersion, the averaged particle sizes measured by DLS decreased from 464 nm to 219 nm, and to 158 nm,
in the order of HA–NH2 , HA–Br and HA–PLLA. The size distribution was also narrowed down in the same trend as shown in
Fig. 8d.
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J. He et al. / Applied Surface Science 258 (2012) 6823–6830
Fig. 8. TEM images of (a) HA–NH2 , (b) HA–Br, and (c) HA–PLLA, and (d) DLS analysis of HA–NH2 , HA–Br and HA–PLLA.
3.4. Biomineralization study of PLLA/HA nanocomposites
The good dispersion of HA–PLLA nanohybrids provided a
necessary prerequisite to prepare well-defined PLLA/HA nanocomposites. By mixing a certain amount of HA–PLLA and PLLA in
chloroform and solution casting, PLLA/HA–PLLA nanocomposites
with 10 wt% and 30 wt% of HA were prepared. These HA-containing
composite matrixes were targeted for bone regeneration. To predict the effect of dispersibility of HA nanoparticles in PLLA matrix
on bone bonding ability, the biomineralization property of the
PLLA/HA–PLLA composite films had been studied using 1.5 SBF. The
PLLA/HA composite films from commercial HA nanoparticles were
also made as the control under the similar conditions. As shown
in Fig. 9, the PLLA/HA–PLLA nanocomposites could induce mineralite depositions much faster than the control PLLA/HA composites
at the same soaking time. Such phenomenon should be related
with the dispersibility of HA nanoparticles. The evenly distributed
HA–PLLA nanoparticles in PLLA matrix might provide more nucleation sites for apatite formation on the film surface. In addition, the
amount of the deposited mineralites increased with the increasing
HA content in composites. After immersed in 1.5 SBF just for 3 days,
the PLLA/HA–PLLA composite film surface had been covered completely by apatite depositions (Fig. 10). According to the analysis of
EDX, the Ca/P ratios of the deposited apatite showed an ascending
trend with prolonging the soaking time, and finally reach a value
to that of natural HA components in bone tissue (a kind of calciumdeficient HA) [9,31–33]. These results suggested that the amount
and dispersibility of HA nanoparticles in polymeric matrix played
a vital role in determining the bone bonding ability and promoting
the applications as bone regeneration substrates.
Fig. 9. Surface morphologies of different composites cultured in 1.5 SBF at 37 ◦ C for 2 days: (a) pure PLLA, (b) PLLA/HA (containing 10 wt% of HA), (c) PLLA/HA–PLLA (containing
10 wt% of HA), (d) PLLA/HA (containing 30 wt% of HA), and (e) PLLA/HA–PLLA (containing 30 wt% of HA). The insets show the morphologies of different composites before
biomineralization.
J. He et al. / Applied Surface Science 258 (2012) 6823–6830
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Fig. 10. Surface morphologies and element analysis (by EDX) of PLLA/HA–PLLA composites containing 30 wt% of HA for (a) 1 day, (b) 2 days, and (c) 3 days.
4. Conclusions
Surface-initiated ATRP of PLLA-MAs had been successfully be
explored for the functionalization of HA nanoparticles. The dispersibility of the resultant HA–PLLA hybrids in composites had
been significantly improved. Compared to the aggregated and
unmodified HA, the good dispersibility of HA–PLLA nanohybrids in
PLLA matrix could make the PLLA/HA–PLLA nanocomposites induce
apatite formation much faster than PLLA/HA composites. With the
versatility of ATRP, properly grafting oligomeric PLLA chains from
HA nanoparticle surfaces is an effective design means of novel
HA–polymer biohybrids for future bone tissue engineering applications.
Acknowledgments
The authors acknowledged the financial support from National
Basic Research Program of China (2012CB933904), National
High Technology Research and Development Program of China
(2011AA030102), National Natural Science Foundation of China
(Nos. 51073016 and 51173014), and Program for New Century
Excellent Talents in University (NCET-11-0556 and NCET-10-0203).
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