Degradable and electroactive hydrogels with tunable electrical conductivity and swelling behavior

Article abstract of DOI:10.1021/cm103498s

Degradable electrically conducting hydrogels (DECHs), which combine the unique properties of degradable polymers and electrically conducting hydrogels, were synthesized by introducing biodegradable segments into conductive hydrogels. These DECHs were obta

Full text of DOI:10.1021/cm103498s

ARTICLE
pubs.acs.org/cm
Degradable and Electroactive Hydrogels with Tunable Electrical
Conductivity and Swelling Behavior
Baolin Guo, Anna Finne-Wistrand, and Ann-Christine Albertsson*
Department of Fibre and Polymer Technology, School of Chemical Science and Engineering, Royal Institute of Technology,
SE-100 44, Stockholm, Sweden
S Supporting Information
b
ABSTRACT: Degradable electrically conducting hydrogels
(DECHs), which combine the unique properties of degrad-
able polymers and electrically conducting hydrogels, were
synthesized by introducing biodegradable segments into
conductive hydrogels. These DECHs were obtained by
joining together the photopolymerized macromer acrylated
poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (AC-
PLA-PEG-PLA-AC), glycidyl methacrylate (GMA), ethylene
glycol dimethacrylate (EGDMA) network and aniline tetra-
mer (AT) by the coupling reaction between AT and the GMA.
The electrical conductivity and swelling behavior of these DECHs were tuned by changing the AT content in the hydrogels, the
cross-linking degree, and the environmental pH value. The good electroactivity and thermal stability of these hydrogels were
demonstrated by UV-vis spectroscopy, cyclic voltammetry, and TGA tests. The chemical structure and morphology of these
polymers were characterized by NMR, FT-IR, SEC, and SEM. These hydrogels possessing both degradability and electrical
conductivity represent a new class of biomaterial and will lead to various new possibilities in biomedical applications.
KEYWORDS: degradable and conductive hydrogels, electroactive and biodegradable polymers, conductive polymers, tissue
engineering
’ INTRODUCTION
also exhibit better solubility, greater hydrophilicity, and better
processability than polyaniline and polypyrrole. However, the
synthesis of DECPs remains a challenge. There are linear, star-
shaped, and hyperbranched architecture of DECPs, but so far no
cross-linked network of DECPs has been reported.
The third-generation biomaterials, once implanted, will help
the body heal itself and are designed to induce specific cellular
responses at the molecular level.1 Third-generation biomaterials
combine the separate concepts of bioactive materials and resorb-
able materials. Recent studies have demonstrated that electrical
stimuli can adjust a range of cellular activities, such as cell ad-
hesion, migration, and proliferation.2-5 Inherently electrically
conductive polymers such as polyaniline and polypyrrole are
widely used in the biomedical field,6-8 but they are not degrad-
able. The degradable electrically conducting polymers (DECPs)
possessing both electrical conductivity and degradability are
therefore attracting great attention.9-13 For instance, erodible
conducting polymers consisting of β-substituted pyrrole mono-
mers with ionizable and/or hydrolyzable side groups were
synthesized by Langer et al.9 Schmidt et al.10 connected con-
ducting oligomers of pyrrole and thiophenes by degradable ester
linkages, and the copolymers showed good conductivity, degrad-
ability, and biocompatibility. We have synthesized star-shaped12
and hyperbranched13 copolymers composed of polylactide,
polycaprolactone, and aniline oligomers, carboxyl-capped aniline
trimer, and aniline pentamer, which are electroactive and degrad-
able. We found that macromolecular architecture is a useful tool
to enhance the conductivity of the polymers. These copolymers
Hydrogels, three-dimensional cross-linked hydrophilic poly-
mer networks, represent an important class of biomaterials, because
of their rubbery nature similar to soft tissues, their easy control of
oxygen, nutrients, and other bioactive molecules, and their excellent
biocompatibility as reviewed by Lee and Mooney14 and Langer
et al.15 During the past couple of decades, hydrogels have attracted
much attention; many hydrogels with different structures, composi-
tions, and properties have been designed and fabricated, and they are
widely used in the biomedical field. Our group has synthesized a
series of biodegradable hydrogels from functional aliphatic polyesters
and renewable resources.16-19 One of the recent trends in hydrogel
synthesis is to use photopolymerization20-23 or phase transition24,25
to form in situ hydrogels. Photopolymerization reactions maintain
good spatial and temporal control over the gelation reaction and can
be carried out under ambient or physiological conditions.18,19,26,27
Photopolymerized hydrogels have already been used for biomedical
applications such as drug delivery28,29and cell transplantation.30,31
Received: October 29, 2010
Published: January 12, 2011
r
2011 American Chemical Society
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Electrically conducting hydrogels (ECHs) which are poly-
meric blends or co-network biomaterials have been developed
recently by Guiseppi-Elie and Wilson32,33 and Wallace et al.34
ECHs combined the unique advantages of redox, optical switch-
ing, and electrical properties of inherently conducting polymers,
the facile diffusivity of small molecules, and high degree of
hydration and good biocompatibility of hydrogels. ECHs origi-
nating from the inherent properties of the constituent compo-
nents possess the biologically relevant properties for devices.33,35-37
For example, polypyrrole/poly(styrene sulfonate sodium salt)
could be used as an effective ion-exchange material for the
ON-OFF switching release of biologically relevant cations.38,39
Conducting electroactive hydrogels composed of 2-hydroxy
ethyl methacrylate and polypyrrole were synthesized, and these
hydrogels, by the introduction of analyte-specific enzymes, had
a potential application as biomedical diagnostic biosensors.40
However, none of the reported electrically conducting hydrogels
is degradable, which severely limits their application in the
biomedical field where degradation is desirable or even necessary
in more advanced tissue engineering application.
HCl mixture, as shown in Scheme 1. The NMR spectrum of AT is shown
in Figure 1. 1H NMR (400 MHz, DMSO-d6): 8.38 (s, 1H), 7.24 (t, 2H),
7.09 (s, 4H), 7.03-6.96 (m, 5H), 6.91-6.80 (m, 2H), 6.82-6.79 (m,
2H), 6.61-6.60 (m, 2H), 5.53 (s, 2H). These results agree well with
data in the literature.41 There is only one peak at 5.53 ppm, and no peak
at 4.69 ppm, indicating that only one isomer as shown in Scheme 1 exists
in the DMSO solution.41
Synthesis of AC-PLA-PEG-PLA-AC Macromonomer.
Macromonomer AC-PLA-PEG-PLA-AC was synthesized as describ-
ed in a previous publication.43 Briefly, the PLA-PEG-PLA copolymer
was obtained by a ring-opening polymerization with D,L-lactide (1 g)
initiated by PEG6000 (3 g) and Sn(Oct)2 (8 mg) as a catalyst at 110 °C
for 48 h. The purified PLA-PEG-PLA copolymer was then acrylated
by acryloyl chloride with triethylamine as the catalyst in dichlorometha-
ne. The AC-PLA-PEG-PLA-AC was then precipitated in cold ether and
filtered. The AC-PLA-PEG-PLA-AC was dissolved in CHCl3, and the
triethylamine was then extracted three times in deionized water and
precipitated in ether. After filtration, the AC-PLA-PEG-PLA-AC was
dried in a vacuum oven for 48 h.
Synthesis of Degradable AC-PLA-PEG-PLA-AC/GMA Hy-
drogels by Photopolymerization. Appropriate amounts (see
Table 1) of macromer AC-PLA-PEG-PLA-AC, GMA, EGDMA, photo-
initiator DMPA (1.5 wt % of all the monomers), and THF as solvent
were weighed and transferred to a small vial. The solution was then
placed under UV-lamp. The distance between the vials and lamp was
about 20 cm. Photopolymerization was subsequently conducted using
an Osram Ultra-Vitalux 300-W lamp which provided homogeneous
solar-like illumination with an irradiation intensity of 80 mW/cm2. The
reaction was maintained for 1 h as shown in Scheme 1. The cross-linked
network was obtained after evaporation of THF. The hydrogel was then
placed in distilled water for 2 days to remove the unreacted monomer,
the water being changed from time to time.
Synthesis of Degradable and Conductive AC-PLA-PEG-
PLA-AC/GMA/AT Hydrogels. Different amounts of AT as shown in
Table 1 were added to the above solution before evaporation of THF.
The coupling reaction between the amino group of AT and the epoxy
group of GMA was carried out at 50 °C for 12 h.44,45 After the reaction,
the THF was evaporated at room temperature. The hydrogel was immersed
in a water/THF mixture to remove unreacted AT and monomers. Finally
the hydrogels were dried in a vacuum oven for 3 days. The synthetic route
is shown in Scheme 1.
On the basis of early experience of DECPs12,13 and degradable
(hydro)gels,16-19 our objective was thus to develop the complete
degradable electrically conducting hydrogels (DECHs) by in-
troducing biodegradation properties into the electrically con-
ducting hydrogels. We hypothesize that DECHs combining the
advantages of degradable electrically conducting polymers and
the unique properties of hydrogels will open a novel exciting area
of third generation biomaterials. We designed and synthesized
the first example of DECH, AC-PLA-PEG-PLA-AC/GMA/AT,
and these DECHs have tunable electrical conductivity and a
controlled hydration percentage. These DECHs were synthe-
sized by a two-step reaction. First, we used photopolymerization
to obtain a degradable network of the macromer AC-PLA-PEG-
PLA-AC/EGDMA/GMA to introduce the epoxy group into the
network, and the well-defined structured aniline tetramer (AT)
monomer was then covalently linked to the network by the
coupling reaction between the amino group of AT and the epoxy
group in GMA. The electrical conductivity and hydration
percentage of the obtained hydrogels were tuned by the AT
content, cross-linking degree, and surrounding pH, which pro-
vide a wide range of choice for any specific biomedical applica-
tion, such as controlled drug delivery systems, neural, bone,
muscle, ear, and cardiovascular tissue regeneration.
The degradable conductive hydrogels with different degrees of cross-
linking were synthesized by adding different amounts of EGDMA to the
system with the AT content of 20 wt %. These samples were coded as 5%
EGDMA hydrogel, 10% EGDMA hydrogel, 20% EGDMA hydrogel, and
30% EGDMA hydrogel, respectively, which means that the EGDMA
amounts were 5%, 10%, 20%, and 30% by weight of the macromer AC-
PLA-PEG-PLA-AC.
’ EXPERIMENTAL SECTION
Materials. D,L-Lactide was recrystallized in dry toluene and subse-
quently dried under reduced pressure (10-2 mbar) at room temperature
for at least two days before polymerization. Toluene (Lab-Scan, 99.8%)
was dried over a Na wire before use. Stannous octoate, Sn(Oct)2 (Sigma-
Aldrich, Sweden) was dried over molecular sieves prior to use. Glycidyl
methacrylate (GMA), ethylene glycol dimethacrylate (EGDMA), poly-
ethylene glycol 6000 (PEG6000), acryloyl chloride (AC), triethylamine,
dichloromethane, photoinitiator 2,2-dimethoxy-2-phenylacetophenone
(DMPA), N-phenyl-1,4-phenylenediamine, ammonium persulphate
((NH4)2S2O8), ammonium hydroxide (NH3OH), hydrochloric acid
(HCl), dimethyl sulphoxide (DMSO), diethyl ether, chloroform
(CHCl3), and tetrahydrofuran (THF) were all purchased from Aldrich
and were used without further purification.
Characterization. FT-IR spectra of the AC-PLA-PEG-PLA-AC/
GMA mixture, the AC-PLA-PEG-PLA-AC/GMA solution after UV
photo-cross-linking, and the AT and the AT-coupled AC-PLA-PEG-
PLA-AC/GMA hydrogel (AC-PLA-PEG-PLA-AC/GMA/AT) were
recorded using a Perkin Elmer Spectrum 2000 spectrometer (Perkin-
Elmer Instrument, Inc.) in the range of 4000-600 cm-1. Each spectrum
was taken as the average of 16 scans at a resolution of 4 cm-1
.
1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were obtained
using a Bruker Avance 400 MHz NMR instrument with CDCl3 as the solvent
at room temperature for the PLA-PEG-PLA and AC-PLA-PEG-PLA-AC
samples and internal standard (δ = 7.26 and 77.0 ppm) and DMSO-d6 as
solvent for the AT sample and internal standard (δ = 2.50 ppm).
Molecular weights of the macromonomer PLA-PEG-PLA and AC-
PLA-PEG-PLA-AC were determined by size exclusion chromatography
(SEC) using a TDA Model 301 equipped with one or two GMHHR-M
columns with TSK-gel (Tosoh Biosep), a VE 5200 GPC Autosampler, a
Synthesis of Aniline Tetramer (AT). AT was synthesized
according to refs 41 and 42. Briefly, N-phenyl-1,4-phenylenediamine was
oxidized by equivalent amounts of (NH4)2S2O8 in an acetone/1 mol/L
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Scheme 1. Schematic Synthesis of the Degradable and Electroactive Hydrogels
Figure 1. 1H NMR of aniline tetramer in DMSO-d6.
VE 1121 GPC Solvent pump and a VE 5710 GPC Degasser, all of which
were from Viscotek Corp. THF was used as the mobile phase (flow rate
1.0 mL/min), and the test was carried out at 35 °C. The SEC apparatus
was equipped with a differential refractive index detector and differential
viscometer. A linear polystyrene standard was used to calibrate the SEC
apparatus.
The UV-vis spectra of AT, the AC-PLA-PEG-PLA-AC/GMA/AT
hydrogel, and their corresponding HCl-doped solutions were recorded
with a UV-vis spectrophotometer (UV-2401).
The hydration percentage (HP) of the hydrogels was determined by
immersing the dry hydrogels in aqueous solutions of the desired pH in
sealed containers. The hydrogels were removed from the aqueous
solution after regular periods of time, weighed, and returned to the
same container after the removal of excess surface water with filter
paper, until swelling equilibrium was reached. HP is calculated as HP =
[(Ws - Wd)/Wd] ꢀ 100%, while sol fraction is determined by sol
fraction = [(Wi - Wd)/Wd] ꢀ 100%, where Wi, Ws, and Wd are the
weight of dried hydrogel after cross-linking, the weight of hydrogel
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Table 1. Feed Compositions of the Hydrogels with Different
AT Contents
5.14 ppm assigned to the -CH- group of PLA with that of the
peak at 3.59 ppm corresponding to the -CH2- group of PEG
segment, and the value is 8. Thus, the molecular weight of the PLA-
PEG-PLA copolymer calculated by NMR was 7075. This is very
close to the molecular weight of 7200 obtained from SEC. The
polymer PLA-PEG-PLA also has a narrow molecular weight
distribution of about 1.27. In the case of the AC-PLA-PEG-PLA-
AC macromer, the three peaks between 6.09 ppm and 5.84 ppm
(seeSupportingInformation), which are assigned to the protons
of the acrylate, confirmed the successful acrylation reaction
between the PLA-PEG-PLA and the acryloyl chloride. This
reaction was also confirmed by the 13C NMR spectrum of AC-
PLA-PEG-PLA-AC, in which two new peaks at 131.9 ppm and
127.5 ppm are ascribed to the unsaturated carbon. The percen-
tage of acrylation of AC-PLA-PEG-PLA-AC was calculated by
comparing the integral of peak at 4.25 ppm corresponding to the
-CH2- chain end of PEG with that of peaks at 5.84-6.44 ppm
assigned to the double bond. The AC-PLA-PEG-PLA-AC has a
quite high acrylation percentage which is 98%. The molecular
weight of AC-PLA-PEG-PLA-AC determined by SEC was 7800,
and polydispersity was 1.21. All these data show the successful
synthesis of the macromonomer AC-PLA-PEG-PLA-AC.
Synthesis of DECHs. Since AT is a free radical inhibitor,50
using free radical polymerization to incorporate AT into poly-
mers does not work without the protection of the -NH- groups
in AT by tert-butoxycarbonyl groups,51 and it needs to deprotect
the tert-butoxycarbonyl group in the polymer by heating to about
200 °C or by acid catalyzed hydrolysis, which is not suitable for
biomaterials. We first introduced GMA with its epoxy group into
the network, and the AT segments were then chemically linked
to the network by the coupling reaction between the amino
group in AT and the epoxy group in GMA for the synthesis of
DECHs. The AT segments during the degradation of the hy-
drogels would be consumed by macrophages, reducing the long-
term adverse response.10 By changing the AT content and the
EGDMA content in the network, we obtained a series of AC-
PLA-PEG-PLA-AC/GMA/AT hydrogels with different conduc-
tivities and different HPs. FT-IR was used to trace the formation
of these DECHs. The FT-IR spectra of the macromer AC-PLA-
PEG-PLA-AC/GMA mixture, the AC-PLA-PEG-PLA-AC/
GMA mixture after UV irradiation, and the AT and the AC-
PLA-PEG-PLA-AC/GMA/AT hydrogel are shown in Figure 2 as
curves a, b, c, and d, respectively. The peak at 1636 cm-1
corresponding to the double bonds (CdC) in the AC-PLA-
PEG-PLA-AC/GMA mixture is clearly seen in curve a. However,
such a peak was absent in curve b after the UV irradiation for 60
min, indicating that photopolymerization had taken place be-
tween the AC-PLA-PEG-PLA-AC, GMA, and EGDMA. At the
same time, a new peak at 909 cm-1 which is assigned to the epoxy
group in the GMA is evident in curve b. The peak of the epoxy
group disappeared completely in curve d, while new peaks at
1597 cm-1 and 1495 cm-1 corresponding to the benzene ring
and the quinoid ring in AT appeared. Furthermore, the char-
acteristic absorbance peaks at 3367 cm-1 and 3192 cm-1 of the
amine -NH2 group in AT in curve c changed into a single peak at
3320 cm-1 in curve d, due to the formation of the imine -NH-,
indicating that the coupling reactions between the epoxy group
and the amino group of AT had occurred. The AT segments
were thus successfully covalently linked to the AC-PLA-PEG-
PLA-AC/GMA network. All these results demonstrated that
the AC-PLA-PEG-PLA-AC/GMA/AT hydrogels were success-
fully synthesized.
sample name
10% AT
hydrogel
20% AT
hydrogel
30% AT
hydrogel
40% AT
hydrogel
components
m(AC-PLA-PEG-
PLA-AC) (mg)
m(EGDMA) (mg)
m(GMA) (mg)
m(DMPA) (mg)
m(AT) (mg)
400
400
400
400
40
21
9.2
52
40
47
40
90
40
156
11.9
400
9.7
120
10.6
230
at swollen state, and the weight of the dried hydrogels after swelling,
respectively.
Thermogravimetric analysis (TGA) of the hydrogel samples was used
to determine the AT content and the thermal stability of the hydrogels.
The TGA test was carried out with a heating rate of 10 °C/min from
30 to 800 °C under a nitrogen atmosphere (nitrogen flow rate 50 mL/min).
The morphology of the hydrogels mounted on metal stubs was exam-
ined using a field emission scanning electron microscope (FE-SEM,
S-4300, Hitachi, Japan).
Cyclic voltammetry (CV) of AT and a highly swollen 5% EGDMA
hydrogel solution was conducted on an Electrochemical Workstation
employing a three-electrode system with a platinum disk as working
electrode (surface area 0.14 cm2), a platinum wire as auxiliary electrode,
and an Ag/AgCl as reference electrode. The scan rate was 60 mV/s for all
the samples. The AT monomer and hydrogel samples were dissolved or
swelled in a DMSO for 24 h. The solutions were doped with 1 mol/L HCl
and were then deoxygenated for 10 min with nitrogen prior to the
electrochemical measurements. The electrical conductivity of the 1 mol/
L HCl doped hydrogel pellets dried in a vacuum oven was determined by
the standard Van Der Pauw four-probe method.46,47 The compressed
pellets with a diameter of 2.0 cm and a thickness of 0.045 cm were made in a
compression mold equipment at 40 °C with a pressure of 50 KN/m2. The
conductivity of each sample was determined four times at different current
values, and the average value was taken as the conductivity of the sample.
’ RESULTS AND DISCUSSION
Synthesis of the AC-PLA-PEG-PLA-AC Macromonomer.
Hydrogels obtained from the photopolymerization of macro-
molecular monomers are an important kind of biomaterial that
are increasingly being applied as in situ materials for cell
encapsulation and tissue regeneration.48,49 The AC-PLA-PEG-
PLA-AC has good hydrophilicity, biocompatibility, and biode-
1
gradability. The H and 13C NMR spectra of AC-PLA-PEG-
PLA-AC are shown in Supporting Information. 1H NMR
(400 MHz, CDCl3) δ = 6.40-6.44 (d, 2H, CH2dC;
COO; (trans)), δ = 6.09-6.16 (d, 1H, ;CdCH;COO),
δ = 5.84-5.86 (d, 2H, CH2dC;COO; (cis)), δ = 5.14 (m,
H, ;CH;), δ = 4.24 (t, 2H, ;CH2;), δ = 3.59 (s, 2H,
;CH2;O), δ = 1.52 (d, 3H, ;CH3). 13C NMR (100 MHz,
CDCl3) δ = 169.5 (;CO;), δ = 165.3 (;OOC;CH2dC;),
δ = 131.9 (CH2dCH;), δ = 127.5 (;CH2dCH;), δ = 70.5
(;CH2;CH2;O), δ = 68.7 (;CH;), δ = 64.4 (;CH2;),
δ = 16.7 (;CH3). The presence of the peak at 4.24 ppm cor-
responding to the methylene proton of PEG6000 at the linkage
between PEG and PLA demonstrates the formation of PLA-PEG-
PLA block copolymer. The average number of LA units in the PLA
blocks was determined by comparing the integral of the peak at
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Figure 2. FT-IR spectra of (a) macromer AC-PLA-PEG-PLA-AC/
GMA mixture, (b) AC-PLA-PEG-PLA-AC/GMA mixture after UV
irradiation, (c) aniline tetramer, and (d) AC-PLA-PEG-PLA-AC/
GMA/AT hydrogel.
Figure 4. Cyclic voltammograms of (a) AT and (b) 5% EGDMA
hydrogel in DMSO solution doped with 1 mol/L HCl, scan rate 60 mV/s.
Scheme 2. Molecular Structure of AT Monomer in Various
Oxidation and Isomer States
Figure 3. UV spectra of (a) AT, (b) HCl-doped AT, (c) 5% EGDMA
hydrogel, and (d) HCl-doped 5% EGDMA hydrogel in DMSO solution.
Electrochemical Properties of Hydrogels. The electroche-
mical properties of the monomer and of the hydrogels were
investigated by UV spectrometry and cyclic voltammetry.
DMSO is a good solvent for all the components of the hydrogel.
5% EGDMA hydrogel with a very low cross-linking density can
swell considerably and partially dissolve in DMSO, and this
makes it possible to study the electrochemical properties of these
hydrogels. The UV spectra of (a) AT, (b) HCl-doped AT, (c) 5%
EGDMA hydrogel, and (d) HCl-doped 5% EGDMA hydrogel
are shown in Figure 3. The UV spectra of both AT and 5%
EGDMA hydrogel show two absorbance peaks at about 318
and 600 nm, which are ascribed to the π-π* transition of the
benzene ring and the benzenoid (B) to quinoid (Q) πB-πQ
excitonic transition.52 Obviously, compared with the Q/B in-
tensity ratio of AT, the ratio of the 5% EGDMA hydrogel
decreased dramatically together with a slight blue shift, which
is probably because the -NH-CH2- group is an electron-
withdrawing group compared to -NH2, which reduces the elect-
ronic concentration of the quinone units, and this also confirmed
that the coupling reaction between the amino group and epoxy
group had occurred. When AT was doped with HCl solution, two
new absorption peaks appeared at 426 and 797 nm, and there was
a slight blue shift of the benzenoid absorption peak to 309 nm
due to the formation of delocalized polarons; however, the UV
spectrum of doped 5% EGDMA hydrogel showed only one new
peak at 429 nm compared to that of AT, which is also probably
due to the formation of a positive induction group -NH-CH2-
from the coupling reaction between the amino group -NH2
of AT and the epoxy group in the hydrogel network.
Figure 4 shows the cyclic voltammograms of (a) the monomer
AT and (b) the 5% EGDMA hydrogel. In Figure 4a, there are
three pairs of oxidation/reduction peaks at 0.30 V, 0.46 V, and
0.65 V for AT, and the proposed mechanism of the changes of
molecular structure are shown in Scheme 2. The first two peaks
at 0.30 and 0.46 V are assigned to the transition from the
leucoemeraldine base state to the emeraldine I and emeraldine II
states. The emeraldine I state will transform into the emeraldine
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Scheme 3. Molecular Structure of AT Segments in 5%
EGDMA Hydrogel in Various Oxidation States
Table 2. AT Content and Conductivity of the Hydrogels
sample name
AP content by TGA
conductivity (S/cm)
10% AT hydrogel
20% AT hydrogel
30% AT hydrogel
40% AT hydrogel
9.4%
19.1%
30.3%
39.2%
4.69 ꢀ 10-7
4.97 ꢀ 10-6
7.89 ꢀ 10-5
1.05 ꢀ 10-4
II state by isomerization, since only the emeraldine II state exists
in the DMSO solution, as indicated by the 1H NMR spectrum of
AT in Figure 1. The third oxidation peak at 0.65 V corresponds to
the transition from the emeraldine II state to the pernigraniline
state (Scheme 2). However, the cyclic voltammogram of the 5%
EGDMA hydrogel exhibited two oxidation peaks at 0.38 and
0.69 V, which are probably ascribed to the transition from the
leucoemeraldine base state to the emeraldine I or emeraldine II
states and from the emeraldine I or emeraldine II state to the
pernigraniline state, as shown in Scheme 3. The higher oxidation
potential of the hydrogel, 0.69 V, compared to the 0.65 V of
AT could also be due to the positive induction effect of
the -NH-CH2- group compared to the -NH2 group, which
stabilizes the AT segments in the hydrogel and increases the
oxidation energy barrier between the emeraldine state to the
pernigraniline state. We speculate that when the leucoemeraldine
base was oxidized to the emeraldine state, only one kind of
emeraldine state (emeraldine I or emeraldine II) was formed,
because the chemical structure of the AT was changed after the
coupling reaction with the epoxy group, which has a steric
hindrance and positive induction effect on the AT segment,
and the possible mechanism is still being investigated. Our CV
results for the 5% EGDMA hydrogel with AT segments are
different from other reports51,53 where only one oxidation peak
was observed for AT segments, probably because the ureido and
amide groups are much stronger electron-withdrawing groups
than the -CH2- group. All these UV spectra and CV curves
demonstrated that these conductive hydrogels have good elec-
troactivity.
Electrical Conductivity of the Hydrogels. The electrical
conductivities of the hydrogels with different AT contents after
doping with the same amount of 1 mol/L HCl were determined
using a standard four probe technique, and the results are listed in
Table 2. The conductivities of the hydrogels with AT contents
from 40 wt % to 10 wt % are between 1.05 ꢀ 10-4 and 4.69 ꢀ
10-7 S/cm, which is lower than that of AT films. This is because
the nonconjugated AC-PLA-PEG-PLA-AC, GMA, and EGDMA
components were introduced into the hydrogel network. How-
ever, these conductivity values are adequate to transfer bioelec-
trical signals in vivo, since the microcurrent intensity in the
human body is quite low.54 It was also found that the electrical
conductivity increased with increasing AT content in the hydro-
gels. This is probably because the AT segments in the network
allowed better p-π stacking of the AT moieties with a higher AT
Figure 5. TGA thermograms of (a) AC-PLA-PEG-PLA-AC, (b) AC-
PLA-PEG-PLA-AC/GMA after UV irradiation, (c) 10% AT hydrogel,
(d) 20% AT hydrogel, (e) 30% AT hydrogel, and (f) 40% AT hydrogel.
Figure 6. Effect of AT content on the hydration percentage of the
hydrogels: (a) AC-PLA-PEG-PLA-AC hydrogel, (b) 10% AT hydrogel,
(c) 20% AT hydrogel, (d) 30% AT hydrogel, and (e) 40% AT hydrogel.
content in the polymer matrix and so facilitate hopping. A broad
range of electrical conductivities of these hydrogels was obtained
by changing the AT content, which provides wide choices for
specific applications.
Thermal Properties of the Hydrogels. The thermal proper-
ties of the macromonomer and hydrogels were studied by TGA,
and the TGA curves are shown in Figure 5. AC-PLA-PEG-PLA-
AC (curve a) started to lose weight at about 180 °C and was
almost totally degraded at 420 °C. Compared with AC-PLA-
PEG-PLA-AC, the UV-cross-linked AC-PLA-PEG-PLA-AC/
GMA hydrogel has a much higher thermal stability in curve b
in Figure 5, because the hydrogel network restricts the motion of
the macromolecular chains, which also indicated that the UV-
photo-cross-linked reaction has taken place, as demonstrated by
FT-IR in Figure 2. In the case of the conductive hydrogels, the
degradation was in a two-step process. The first obvious weight
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Figure 7. SEM images of the hydrogels: (a) surface of AC-PLA-PEG-PLA-AC/GMA, (b) cross-section of AC-PLA-PEG-PLA-AC/GMA, (c) 10% AT
hydrogel, (d) 20% AT hydrogel, (e) 30% AT hydrogel, and (f) 40% AT hydrogel.
loss occurred between 100 °C and 420-455 °C for hydrogels
with different AT contents. From 100 °C, the slight weight loss
of the conductive hydrogel is ascribed to the loss of solvent and
water trapped in the hydrogel network. The AC-PLA-PEG-PLA-
AC, GMA, and EGDMA components completely degrade when
the temperature rose to 420-455 °C. The second evident weight
loss of the hydrogels from 420 to 455 °C is assigned to the
degradation of the AT segments linked to the hydrogel network.
The starting temperatures for the degradation of 10% AT
hydrogel, 20% AT hydrogel, 30% AT hydrogel, and 40% AT
hydrogel were 420 °C, 440 °C, 450 °C, and 455 °C, respectively,
indicating that the thermal stability of the hydrogels increased
with increasing AT content in the hydrogel, probably due to
the greater thermal stability of the AT segments. The AT
contents in the hydrogels were calculated using the TGA curves
by taking the residual weight of 10% AT hydrogel, 20% AT
hydrogel, 30% AT hydrogel, and 40% AT hydrogel at 420 °C,
440 °C, 450 °C, and 455 °C and subtracting the weight of
cross-linked AC-PLA-PEG-PLA-AC hydrogel at the same tem-
perature, and the results are listed in Table 2. It was found that
the data obtained from TGA curves were close to the theoretical
values, which also confirms the successful synthesis of the
hydrogels.
Swelling of the Hydrogels. The swelling behavior is impor-
tant for the application of the hydrogels. The HP of the hydrogels
was dependent on the AT content in the hydrogels, the cross-
linking degree, and the pH value of the solution. Therefore, the
HP can be tuned to meet the requirements of a specific ap-
plication. Figure 6 shows the effect of AT content on the HP of
these hydrogels. It was found that the AC-PLA-PEG-PLA-AC
hydrogel swells most rapidly and has the highest HP and that the
HP of the other hydrogels decreased with increasing AT content
in the hydrogel. This is because the AC-PLA-PEG-PLA-AC is
more hydrophilic than the AT segments. The swelling behavior
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Figure 9. Effect of pH on the hydration percentage of hydrogels: red,
pH = 2.1; green, pH = 7.4.
Figure 8. Effect of EGDMA content on the hydration percentage of
the hydrogels.
The HP of the hydrogels is greater at pH 2.1 than at pH 7.4. This
is probably because in an acidic medium (pH 2.1) the AT
segment is doped by the acid, which is associated with hydrated
counteranions that serve to maintain charge neutrality of the
protonated AT moiety.
of the hydrogels can also be explained in term of their morpho-
logy. Figure 7 shows the SEM of these hydrogels with different
AT contents, and it is evident that the AC-PLA-PEG-PLA-AC
hydrogel has a rough and condensed surface, although there are
plenty of particles inside the hydrogel, as observed in the cross-
section of the hydrogel (Figure 7 b). Water molecules can easily
penetrate the free space between the particles and are absorbed
by the hydrogel. This is why the AC-PLA-PEG-PLA-AC hydro-
gel reached its maximum HP (about 300%) most rapidly. The
hydrogel then cracked into small pieces due to its internal particle
structure, and it was difficult to take all the pieces from the water
to be weighed; thus, the HP of the AC-PLA-PEG-PLA-AC/
GMA hydrogel apparently decreases. From Figure 7c-f, it can be
seen that the AT was distributed evenly in the hydrogel matrix
and that the surface became increasingly smooth with increasing
AT content. It is difficult for the water molecules to penetrate
though the smooth surface and into the hydrogels, and the
swelling rate of these hydrogels thus decreases with increasing
AT content in the hydrogels.
It is known that cross-linking agents have significant effects on
the HP of the hydrogels. We added different EGDMA amounts
to tune the HPs of the hydrogels, and the results are shown in
Figure 8. We found that the HP of 5% EGDMA hydrogels
reached about 60 in 10 min and then decreased sharply. This is
probably because the water can penetrate into the hydrogel easily
with lower cross-linking concentration of the hydrogel; however,
the hydrogel partially dissolved because of the low cross-linked
density in the network. The 5% EGDMA hydrogels fractured
into small pieces, and it was quite hard to take them out from the
water to be weighed. These two reasons lead to a decrease in HP
of the 5% EGDMA hydrogels. With EGDMA content increasing
from 10% to 30%, the HP of the hydrogels decreased. The
hydrogels swell more slowly with increasing content of EGDMA,
but all the hydrogels reached swelling equilibrium after about
30 min. Sol fraction of the hydrogel describes the fraction of the
polymer which is not included in the cross-linked network. The
sol fraction of 5% EGDMA hydrogels is about 4%, and the sol
fractions of the 10% EGDMA hydrogel, 20% EGDMA hydrogel,
and 30% EGDMA hydrogel system after swelling 90 min are
around 0.1%, which means the extractables in the hydrogels are
quite limited.
’ CONCLUSIONS
A simple and elegant synthesis route to obtain degradable and
electrically conductive hydrogels (DECHs) has been presented.
A series of DECHs based on acrylated poly(D,L-lactide)-poly-
(ethylene glycol)-poly(D,L-lactide) macromer (AC-PLA-PEG-
PLA-AC) and aniline tetramer (AT) have been synthesized and
characterized by the facile coupling reaction between the epoxy
group of glycidyl methacrylate (GMA) in the network and the
amino group of AT. The electroactivity of these hydrogels was
confirmed by cyclic voltammetry, which showed two pairs of
reduction-oxidation peaks, and the conductivity varied between
1.05 ꢀ 10-4 and 4.69 ꢀ 10-7 S/cm. In addition, it was possible
to tune the hydration percentages from 302% to 18.5% by
changing the cross-linking density or the pH. The possibility of
tuning both the conductivity and the hydration percentage
makes it possible to meet the demands of many specific applica-
tions. These hydrogels which combine biodegradability from the
polyester segment and electroactivity from conducting polymers
will greatly expand the application field of conducting hydrogels
toward new fields. They are promising candidates for the third
generation biomaterials and will open up a range of exciting
potential applications in the biomedical field, including drug
delivery and tissue regeneration.
’ ASSOCIATED CONTENT
Supporting Information. 1H NMR and 13C NMR spectra
S
b
of AC-PLA-PEG-PLA-AC macromer (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*Tel.:þ46-8-790 8274. Fax: þ46-8-20 84 77. E-mail: aila@
polymer.kth.se.
’ ACKNOWLEDGMENT
The pH of the body fluids varies; thus, it is necessary to study
the effect of the pH of the surrounding environment on the HP
of the hydrogels for in vivo applications, and the swelling of
the hydrogels in solution at pH 2.1 and 7.4 is shown in Figure 9.
The authors thank the Swedish Research Council (Grant No.
2008-5538), the China Scholarship Council (CSC), and The
Royal Institute of Technology (KTH) for financial support for
this work.
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