A robust pathway to electrically conductive hemicellulose hydrogels with high and controllable swelling behavior

Article abstract of DOI:10.1016/j.polymer.2014.05.003

A robust pathway to synthesize electrically conductive hemicellulose hydrogels (ECHHs) based on O-acetyl-galactoglucomannan (AcGGM) and conductive aniline tetramer (AT) is presented. These ECHHs were obtained by functionalizing carboxylated AcGGM with gly

Full text of DOI:10.1016/j.polymer.2014.05.003

Accepted Manuscript
A Robust Pathway to Electrically Conductive Hemicellulose Hydrogels with High and
Controllable Swelling Behavior
Weifeng Zhao , Lidija Glavas , Karin Odelius , Ulrica Edlund , Ann-Christine
Albertsson
PII:
S0032-3861(14)00369-3
10.1016/j.polymer.2014.05.003
JPOL 16956
DOI:
Reference:
To appear in: Polymer
Received Date: 11 February 2014
Revised Date: 8 April 2014
Accepted Date: 2 May 2014
Please cite this article as: Zhao W, Glavas L, Odelius K, Edlund U, Albertsson A-C, A Robust Pathway
to Electrically Conductive Hemicellulose Hydrogels with High and Controllable Swelling Behavior,
Polymer (2014), doi: 10.1016/j.polymer.2014.05.003.
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A Robust Pathway to Electrically Conductive Hemicellulose Hydrogels with
High and Controllable Swelling Behavior
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Weifeng Zhao, †, ‡ Lidija Glavas, † Karin Odelius, † Ulrica Edlund, † Ann-Christine
Albertsson,*, †
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†Fiber and Polymer Technology, School of Chemical Science and Engineering, Royal Institute of
Technology (KTH), Teknikringen 56-58 SE-100 44, Stockholm, Sweden
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‡College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials
Engineering, Sichuan University, Chengdu 610065, Sichuan, China
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*Corresponding Author. Tel: +46-8-790 8274. Fax: +46-8-20 84 77. E-mail: aila@kth.se.
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Abstract: A robust pathway to synthesize electrically conductive hemicellulose hydrogels (ECHHs)
based on O-acetyl-galactoglucomannan (AcGGM) and conductive aniline tetramer (AT) is presented.
These ECHHs were obtained by functionalizing carboxylated AcGGM with glycidyl methacrylate
(GMA) and subsequently covalently immobilizing AT onto GMA. Hydrogel swelling ratios (SRs)
were regulated by the degree of substitution (DS) of the carboxylated AcGGM, the maximum varied
as follows: SRDS=1.14< SRDS=0.60< SRDS=0.24. The SR can also be tuned from 548 % to 228 % by
changing the AT contents from 10 % (w/w) to 40 % (w/w) while simultaneously altering
conductivities from 2.93×10-8 to 1.12×10-6. Free-standing ECHHs with tunable conductivity and
degree of swelling, as presented herein, have a broad potential for biomedical applications.
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Keywords: Hydrogels; Hemicellulose; Electrically Conductive; Swelling Behavior; Robust
1. Introduction
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Polymeric hydrogels have defined a remarkable research area, mainly due to their wide range of
applications, such as matrix chemistry and biology [1], the removal of endocrine disruptors [2], media
for the delivery of substances in biomedicine [3], and scaffolds [4]. Hydrogels have potential in
biomedical applications due to their good biocompatibility and ability to selectively mimic human
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tissues [1, 5]. Natural polymer-based hydrogels, such as those made from proteins and
polysaccharides, are widely used in injectable engineering [6], controlled drug release [7, 8],
biosensors [9], and articular cartilage tissue engineering [10] because they are commonly
biocompatible, degradable, capable of promoting cell adhesion and proliferation, and immunologically
inert. Hemicellulose-based hydrogels are currently being acknowledged for their non-toxic and
renewable properties in addition to the advantages of natural polymers mentioned above [11-15].
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The family of hemicelluloses is the second most abundant group of polysaccharides in the vegetal
world after cellulose, representing 15-35 % (w/w) of higher plants and wood [16]. The pendant
hydroxyl groups of the polysaccharide backbone offer a number of possibilities for the chemical
modification of hemicelluloses and for the preparation of materials with new profiles that can increase
the utility of these biopolymers. The preparation of biomedical hemicellulose materials, such as bio-
sorbents and hydrogels, may be useful in key applications, such as heavy metal removal [17], drug
release systems, and tissue engineering [18, 19]. For gymnosperms, glucomannan is the major type of
hemicellulose in the secondary cell wall, where it is also believed to serve a structural function [20].
Due to the abundance, the relatively high degree of acetylation and the low molecular weight of O-
acetyl-galactoglucomannan (AcGGM), in addition to its solubility in water and in dimethyl sulfoxide
(DMSO) and dimethylformamide (DMF), it serves as an attractive renewable material candidate for
the design of hydrogels [13, 19]. AcGGM-derived hydrogels have recently been prepared by a
carbonyldiimidazole (CDI)-assisted coupling reaction between AcGGM and hydroxyethyl
methacrylate (HEMA) followed by cross-linking of the vinyl functional groups. Microspheres
prepared from AcGGM-based hydrogels and loaded with either a small hydrophilic substance
(caffeine) or a macromolecular model protein (bovine serum albumin) showed controlled release in
vitro [14]. Furthermore, it was demonstrated that both the pendant group composition and the enzyme
action are valuable tools in the tailoring of hydrogel release profiles for drug delivery [19]. A series of
crosslinking chemistries for AcGGM-based hydrogels was also developed, and the resulting properties
of the AcGGM gels could be custom-built for a specific performance [13, 21]. However, electrical
conductivity is rarely investigated in hemicellulose-derived materials, although conductivity features
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could promote polymer-cell interactions that would be useful in a wide range of applications in the
biomedical field. For instance, conductive properties have been shown to support the attachment and
differentiation of neural-like cells with improved interactions [22], and biomaterials with electrical
conductivity have the potential to be used in nerve regeneration [23].
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The term conductive polymers (CPs) denotes organic polymers that exhibit similar properties to those
of metals and inorganic semiconductors and are considered as the fourth generation of polymeric
materials [23, 24]. The explosive growth of research on CPs is due to their interesting physical and
chemical properties, such as electrical conductivity, electroluminescence, and electrochromism, which
are useful in a number of practical applications, e.g., photovoltaic devices, light-emitting diodes,
electrochromic displays and biomedical devices [23, 25]. Polyaniline (PANi) and its derivatives are
the most commonly investigated CPs in biomedical engineering. For example, porous tubular
scaffolds fabricated from blends of polycaprolactone (PCL) and a hyperbranched conducting
copolymer show non-cytotoxicity with HaCaT keratinocytes [26]. Guarino et al. demonstrated that
conductive PANi/PEGDA macroporous hydrogels improve the biological response of PC12 and
hMSC cells [23]. One drawback associated with these conductive composites is that the scaffold-
forming components (e.g., PCL and PEGDA) are non-renewable materials. In addition, PANi has poor
solubility in most solvents [27]. One approach to overcoming this predicament is to design aniline
oligomers with biodegradable and renewable resources [25]. Chen et al. developed new biodegradable
electroactive hydrogels with aniline pentamer grafted onto gelatin [28], and aniline pentamer for cross-
linking chitosan [29]. The preliminary study demonstrated that these hydrogels have the potential to
be utilized in drug delivery and tissue engineering. We anticipate that electrically conductive
hemicellulose hydrogels (ECHHs) could be obtained by combining a conductive aniline tetramer with
biodegradable and nontoxic hemicellulose. Therefore, ECHHs provide a potential means to electrically
simulate cells and regulate specific cellular activities to widely extend the applications of CPs in
biomedical fields, such as controlled drug release and nerve regeneration.
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Our aim is to develop a robust synthetic route for ECHHs by covalently attaching conductive aniline
tetramers to AcGGM-derived hydrogels. The introduction of maleic anhydride, glycidyl methacrylate
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and conductive aniline tetramer into the polysaccharide scaffold will alter the swelling ratio and enable
control over the hydrogel properties. Our aim is further to regulate the conductivity by altering the
aniline tetramer content.
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2. Experimental Section
2.1. Materials
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Glycidyl methacrylate (GMA), triethylamine (TEA), maleic anhydride (MA), N-phenyl-p-
phenylenediamine, ammonium persulfate ((NH4)2S2O8), ammonium hydroxide (NH4OH),
hydrochloric acid (HCl), dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMAc) and
tetrahydrofuran (THF) were purchased from Sigma-Aldrich and were used as received, unless
otherwise stated. O-acetyl-galactoglucomannan (AcGGM) originating from spruce (Picea abies) was
extracted from thermo-mechanical pulping (TMP) processed water, purified and concentrated by
ultrafiltration (membrane cutoff 1 kDa), and lyophilized using a Lyolab 300 lyophilizer. The
carbohydrate composition of the AcGGM isolate was 17 mol % glucose, 65 mol % mannose, and 15
mol % galactose. AcGGM had a number average molecular weight (Mn) of approximately 7,500 g
mol-1 (DP ~ 40), a dispersity index (Đ) of 1.3 and a degree of acetylation (DSAc) of 30 %, as
determined by size exclusion chromatography (SEC) calibrated with MALDI-TOF according to a
published protocol [30].
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2.2. Synthesis of Aniline Tetramer
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Aniline tetramer (AT) was synthesized according to a previously described procedure [31]. Briefly, N-
phenyl-p-phenylenediamine (3.68 g, 0.02 mol) was dissolved in a 150 mL mixture of acetone with 1
mol/L HCl (v/v 150:100) at 0 ˚C. Ammonium persulfate (9.12 g, 0.04 mol) in 100 mL of acetone/HCl
solution was then added dropwise to the solution over 30 min. A color change from green to dark blue
was observed, and the reaction was allowed to proceed for another 2 h at 0 ˚C. The mixture was
subsequently filtered, and the filter cake was washed with 1 M HCl and deionized water. The crude
AT was dedoped in 1 M NH4OH for 2 h and then filtered and washed with deionized water until the
filtrate was neutral. Finally, the AT (dark powder, yield 68.5 %) was lyophilized for 3 days.
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2.3. Synthesis of Carboxylated AcGGM (C-AcGGM)
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C-AcGGM was prepared as previously reported [32] with some small modifications (Scheme 1). In
brief, 1 g of AcGGM (~ 5.7 mmol sugar units) was dissolved in 30 mL of pre-dried DMSO at 50 ˚C.
TEA (0.1 mL) and 0.14-0.58 g of MA (1.4-5.7 mmol, 0.25-1 eq) were added. The reaction mixture
was kept at 50 ˚C for 1 h. The reaction was quenched by pouring the reaction mixture into 200 mL of
THF, and the solid residue was collected by centrifugation. The product was washed with 300 mL of
THF and dried under reduced pressure. To investigate the effect of the degree of substitution of MA
on the swelling ratio (SR) of the hemicellulose hydrogels, the precursor C-AcGGM polymers were
prepared with 0.25, 0.5 and 1.0 eq of MA and denoted as C0.25-AcGGM, C0.5-AcGGM and C1.0-
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AcGGM, respectively. The degree of substitution (DS) was determined by H NMR spectroscopy.
Yield: 90-99 %.
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Scheme 1. Proposed synthesis route of electrically conductive hemicellulose hydrogels (ECHHs).
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2.4. Preparation of ECHHs
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ECHHs were prepared by a two-step reaction (Scheme 1) with varying feed compositions (Table 1). In
brief, 200 mg of C1.0-AcGGM was dissolved in 0.8 mL of DMSO followed by the addition of 60 mg
of APS and 100 mg of GMA. The mixture was degassed prior to the reaction. The cross-linking
reaction was conducted at 70 ˚C for 40 min. Subsequently, the formed gel was purified in DMSO to
remove the unreacted residues. The gel was immersed in a DMSO solution with different
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concentrations of AT and kept at 70 ˚C for 12 h followed by washing in DMSO for 48 h. DMSO was
changed frequently (every 2 h in the beginning) to ensure complete removal of unreacted AT. Then, a
H2O/THF mixture (v/v 1:1) was used to remove DMSO. Finally, the ECHHs were dried under vacuum
for 3 days.
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The ECHHs with 10, 20, 30 and 40 % (w/w) AT were annotated according to their equivalent of MA,
the addition of GMA and the % (w/w) of AT. As an example, C1.0-AcGGM/GMA/10%AT contained
200 mg of C1.0-AcGGM, 100 mg of GMA and 10 % (w/w) AT. A gel without AT was synthesized as
a reference sample and denoted C1.0-AcGGM/GMA. The gels prepared from C0.25-AcGGM, C0.5-
AcGGM and C1.0-AcGGM polymers were used to investigate the effect of the degree of substitution
of MA on the swelling ratio (SR) of the hemicellulose hydrogels.
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Table 1. Feed compositions of ECHHs.
Sample codes
C1.0-AcGGM
C0.5-AcGGM
C0.25-AcGGM
mol% of MA C-AcGGM (mg) GMA (mg) DMSO (mL) AT* (mg)
100
50
200
200
200
0.8
0.8
0.8
25
C1.0-AcGGM/GMA
100
100
100
100
100
200
200
200
200
200
100
100
100
100
100
0.8
0.8
0.8
0.8
0.8
C1.0-AcGGM/GMA/10%AT
C1.0-AcGGM/GMA/20%AT
C1.0-AcGGM/GMA/30%AT
C1.0-AcGGM/GMA/40%AT
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130
200
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* The amount of AT in 4 mL of DMSO.
2.5. Characterization
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1H NMR (400 MHz) spectra of AT, AcGGM and C-AcGGM polymers and 13C NMR (400 MHz)
spectra of AcGGM and C-AcGGM polymers were obtained using a Bruker Avance 400 MHz NMR
instrument at room temperature with DMSO-d6 as the solvent and the residual DMSO as the internal
standard (δ=2.50).
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Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) was used to verify the
successful synthesis of AT. MALDI-TOF analyses were performed on a Bruker Ultraflex MALDI-
TOF mass spectrometer with a SCOUT-MTP Ion Source (Bruker Daltonics, Bremen) equipped with a
N2 laser (337 nm), a grid-less ion source, and a reflector design. The positive ion spectra depicted are
representations of the sums of 1000 laser shots. The instrument operated at an acceleration voltage of
25 kV and a reflector voltage of 26.3 kV, and the detector mass range was set to 60-1000 Da. Samples
were prepared by dropping 1-3 ꢀL of samples (1 mg/mL DMSO solution) onto a steel coordinate
plate. MALDI data were collected and analyzed with FlexAnalysis software (Bruker Daltonics).
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FTIR spectra were recorded using a Perkin Elmer Spectrum 2000 spectrometer (Perkin-Elmer
Instrument, Inc.) equipped with a single reflection attenuated total reflectance (ATR) accessory
(golden gate) from Graseby Specac (Kent, UK). FTIR was used to verify the molecular structures of
AT, the AcGGM and C-AcGGM polymers. FTIR was also utilized to verify the successful coupling of
AT to the hemicellulose hydrogels. Each spectrum was recorded as the average of 16 scans at a
resolution of 4 cm-1 in the range between 4000 and 600 cm-1.
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The water contact angle measurements of C1.0-AcGGM, C1.0-AcGGM/GMA and C1.0-
AcGGM/GMA/10%AT hydrogels films were measured using a contact angle and surface tension
meter (KSV instruments Ltd.). A drop of Milli-Q water (5 ꢀL) was placed on the surface of the sample
and images of the water menisci were recorded by a digital camera. The contact angle of each sample
was taken as the average of four measurements at different points.
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Size exclusion chromatography (SEC) was used to determine the molecular weight and dispersity
index (Đ) of AcGGM and C-AcGGM [33]. The samples were analyzed using a Shimidzu RID-10A
SEC equipped with a refractive index detector and three PLgel 20 ꢀm Mixed-A (300 mm × 7.5 mm)
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columns with an injection volume of 200 ꢀL. Dimethylacetamide (DMAc) with 0.05 % (w/w) LiCl
was used as the eluent (0.5 mL/min). The measurements were performed at 80 °C. The SEC system
was calibrated with Pullulan standards with molecular weights ranging from 342 to 800,000 g/mol.
The samples were dissolved in DMAc (0.05 % (w/w) LiCl) by vigorous stirring and filtered (0.45 ꢀm,
Millipore) before injection. LC Solution software from Shimatzu was used for data acquisition and
calculations.
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The swelling ratio (SR) of the hydrogels was determined by immersing pre-weighed dry hydrogels in
buffer solutions (prepared from Na2HPO4 and NaH2PO4, pH=7.4) at room temperature. The weight
gain of the hydrogels was monitored gravimetrically as a function of time. The weights of the samples
in the swollen state at different times t (mt) were measured after gently removing excess water using
filter paper. The SR was calculated using Eq. (1), where m0 denotes the weight of the samples in the
dry state:
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ꢂ ꢄ ꢂ
ꢃ
ꢅ × 100
ꢀ1ꢁ
ꢀ ꢁ
SR % =
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ꢅ
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For the thermal stability of the hydrogels, thermogravimetric analysis (TGA) of the samples was
performed using a Mettler-Toledo TGA/SDTA 851e. Approximately 10 mg of each sample was put
into a 70 ꢀL ceramic cup without a lid. TGA tests were conducted under a nitrogen atmosphere (flow
rate of 50 mL/min) with a heating rate of 10 ˚C/min from 30 to 800 ˚C. The data were collected and
analyzed by Mettler STARe software.
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The cross-section morphology of the hydrogels was observed by Ultra-High Resolution FE-SEM
(Hitachi S-4800). The samples were lyophilized overnight in small vials, cross-sectioned, attached to
the sample supports and coated with a 3 nm gold layer.
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The electrical conductivity of the 1 mol/L HCl-doped hydrogels was determined by the standard Van
der Pauw four-probe method (two reference probes, one counter probe and one working probe) [31,
34]. After doping, the hydrogels were thoroughly dried in a vacuum oven for 48 h. Therefore, the
conductivity of the hydrogel was not affected by water content. Hydrogel pellets, with a diameter of 2
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cm and a thickness ranging from 0.035 to 0.050 cm, were made by compression molding using a
pressure of 30 kN/m2 at 70 ˚C for 10 min.
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3. Results and Discussion
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Hemicellulose-based hydrogels are being developed due to their biocompatibility, nontoxicity and
abundantly renewability [14, 23]. Aniline oligomers exhibit similar conductivity with improved
process-ability compared to metals and inorganic semiconductors [27]. Therefore, a new family of
electrically conductive hemicellulose hydrogels (ECHHs) was developed in this work by combining
O-acetyl-galactoglucomannan (AcGGM) and aniline tetramer (AT). AcGGM was carboxylated with
varying amounts of MA (C-AcGGM) to regulate the swelling behavior of hydrogels. The reaction
pathway was tuned to be robust so that it can be carried out under ambient conditions without
requiring inert atmospheres or dry conditions. Varying amounts of AT were immobilized into the
hydrogels to provide conductivity and further regulate the swelling behavior of hydrogels.
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3.1. Synthesis of AT
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The successful synthesis of AT was verified by NMR and MALDI-TOF mass spectrometry. The H
NMR spectrum of AT is shown in the Supporting Information (Fig. S1). There is a single peak at 5.53
ppm and no peak at 4.69 ppm, indicating that only one isomer exists in the DMSO solution [35]. AT
appeared as a peak at 366.36 m/z in MALDI-TOF mass spectra, which matched its chemical structure.
These results agree with previous reports [31, 35].
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3.2. Synthesis of C-AcGGM Polymers
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To achieve a facile and robust gelation, the heteropolysaccharide AcGGM was modified with MA
under ambient conditions to covalently immobilize double bonds for subsequent in situ gelation. A
series of C-AcGGM with varying degrees of substitution of MA were prepared to tune the swelling
behavior.
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ATR-FTIR spectra confirmed the structural composition of pure AcGGM and C-AcGGM polymers,
Fig. 1. Pristine AcGGM displayed the anticipated C=O stretching at 1730 cm-1 stemming from the
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acetylated pendant groups, a H-O-H deformation vibration of absorbed water at approximately 1643
cm-1, some alkane vibrations in the 1350-1480 cm-1 region, and a hydroxyl band at 3000-3600 cm-1,
Fig. 1A. In contrast, AcGGM modified with MA (C-AcGGM) displayed an increase in band intensity
at 1721 cm-1, attributed to the C=O functionality of the ester linkage. The peaks emerging at 1638,
1581 cm-1 and 950 cm-1 were due to the C=C stretching and deformation vibrations, verifying the
presence of vinyl groups in the modified AcGGM. The peak emerging at 1165 cm-1 was attributed to
the vibration of the methylene group in each substituted C-6 position. All results agree with our
previous reports [13, 32]. The intensity of the peaks at 1721 and 1581 cm-1 increased with an increase
in the MA content (Fig. 1B), indicating the successful coupling of MA to AcGGM. The intensity of
the peaks in the 966-1133 cm-1 region (-C-O-C- vibrations from the sugar units) should remain
constant since there was almost no change for -C-O-C- bonds during the reaction. Therefore, the ratio
(R) of the area of the peaks in the 1674-1776 cm-1 region (A1674-1776) to the area of the peaks in the 966-
1133 cm-1 region (A966-1133) reflects the grafting density (GD) of MA, which is defined in Eq. (2). The
GD increased with the increase of the mole ratio of MA, as shown in Supporting Information (Table
S1).
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ꢆ
ꢄꢆ
ꢇꢈꢉꢊꢋꢋꢌ
ꢉꢊꢋꢋꢌ × 100
ꢀ2ꢁ
ꢀ ꢁ
GD % =
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ꢉꢊꢋꢋꢌ
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Fig. 1. ATR-FTIR spectra of pure and carboxylated AcGGM: split spectra (A) and overlay spectra (B)
of C-AcGGM normalized at 1816 cm-1.
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1H and 13C NMR were further used to confirm the successful coupling of AcGGM with MA and to
determine the degree of substitution (DS) achieved in the reaction (Fig. 2 and Fig. S2). Upon coupling,
additional peaks originating from the double bonds of MA appeared at 6.07 and 6.41 ppm, and a peak
corresponding to the protons from the C-6 position of carboxylated AcGGM appeared at 3.10 ppm. In
the 13C NMR, alkene signals were observed at 128.61 and 132.43 ppm, while the carbonyls originating
from the ester and carboxyl groups were observed at 165.52 and 167.05 ppm, respectively. As
expected, a clear relationship between the DS and the amount of MA was found. As the degree of
acetylation for the AcGGM used was determined to be 0.3 [30], the DS (the degree of carboxyl group
substitution) can be calculated by setting the relative integral of the response of the alkene protons
(6.41 and 6.07 ppm) in relation to the integral of the response of the acetyl protons (2.0 ppm). The DS
increased with increased feed ratios of MA (Table 2).
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Table 2. Yield, number average molecular weight (Mn), dispersity index (Đ) and degree of substitution
(DS) of C-AcGGM polymers.
Sample codes
Feed ratio of MA
(FR)
Yield
(%)
a Mn
b Mn
b DS c Mn
(g/mol)
c Đ
(g/mol)
(g/mol)
AcGGM
4 400
3.07
C0.25-AcGGM 0.25
99
90
99
8 444
8 669
11 575
7 927
8 364
10 249
0.24 5 300
0.60 6 050
1.14 6 000
2.92
2.67
2.22
C0.5-AcGGM
0.5
1.0
C1.0-AcGGM
a
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Calculated from feed ratio, taking the yield into consideration, Mn= 7500×
(1+0.57×FR×98.06)×Yield. b Determined by 1H NMR. c Determined by DMAc-SEC.
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Fig. 2. 1H NMR (A) and 13C NMR (B) spectra of pristine AcGGM and C-AcGGM in DMSO-d6.
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3.3. Preparation of ECHHs
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AT is a free radical inhibitor [36]; therefore, using free radical chemistry to incorporate AT into
polymers is not a viable option unless the NH-groups in AT are protected [37]. There is also a need to
deprotect the tert-butoxycarbonyl group in the polymer by heating or by acidic hydrolysis, methods
that may cause an onset of the degradation of polysaccharides. To address this, we developed an
alternative route involving the introduction of GMA into the hydrogel network. This was followed by
chemical coupling of the AT segments to the network to form ECHHs by reacting the amino group in
AT and the epoxy group in GMA. The hydrogels were prepared in two steps: (1) using ammonium
persulfate to initiate polymerization of a mixture of C1.0-AcGGM and GMA, and (2) immersing the
formed hydrogels in a DMSO solution containing varying amounts of AT. Compared to the
functionalization of polymers with aniline oligomers using N,N`-dicyclohexyl carbodiimide/4-
dimethylaminopyridine (DCC/DMAP) [38] or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
(EDC)/DMAP [39], the pathway presented here is more robust as there is no need to run the reactions
under an inert atmosphere or to perform tedious and chemical-consuming purification procedures.
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The hydrogel color changed from yellow to opaque after adding GMA and then to black after the
reaction with AT due to the color of AT (Fig. 3). Interestingly, the volume of hydrogels decreased in
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each step as a consequence of the hydrophobic nature of GMA and AT. The hydrophilicity of the
hydrogels was systematically investigated and is discussed in the next section. The formed ECHHs
were free-standing, indicating sufficient mechanical integrity for soft tissue scaffold applications (Fig.
3D).
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Fig. 3. Hydrogels based on C1.0-AcGGM (A), C1.0-AcGGM/GMA (B), and C1.0-
AcGGM/GMA/10%AT (C), and free-standing C1.0-AcGGM/GMA/10% AT hydrogel (D).
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ATR-FTIR was used to follow the formation of these ECHHs. The ATR-FTIR spectra of AT, C1.0-
AcGGM, C1.0-AcGGM hydrogel, C1.0-AcGGM/GMA hydrogel and C1.0-AcGGM/GMA/10%AT
hydrogel are shown in Fig. 4. The disappearance of the peak at 950 cm-1 corresponding to the double
bonds (C=C) in the C-AcGGM polymer correlated with the crosslinking via radical polymerization. A
new peak at 903 cm-1 assigned to the epoxy group in GMA is evident in curve C. The epoxy peak
significantly diminished in curve D, while new peaks at 1580 cm-1 and 1500 cm-1 corresponding to the
benzene and quinoid rings in AT, appeared. All of these results demonstrated that the C-
AcGGM/GMA/AT hydrogels were successfully synthesized.
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Fig. 4. ATR-FTIR spectra of C1.0-AcGGM (A), cross-linked C1.0-AcGGM hydrogel (B), C1.0-
AcGGM/GMA hydrogel (C), C1.0-AcGGM/GMA/10%AT hydrogel (D), and AT (E).
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To verify that AT was covalently attached throughout the bulk of the hydrogels, the composition of
C1.0-AcGGM/10%AT was assessed at different positions. The ATR-FTIR spectra of the cross-section
of C1.0-AcGGM/GMA/10%AT hydrogels indicated that the covalently attached AT-containing
hydrogel, C1.0-AcGGM/GMA/10%AT, had equivalent AT intensities (characteristic peaks at
approximately 1580 and 1500 cm-1) from the surface to the center and is therefore homogeneously
modified (Fig. 5).
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Fig. 5. ATR-FTIR spectra for the hydrogel with AT covalently attached, C1.0-
AcGGM/GMA/10%AT, at different positions through the hydrogels.
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3.4. Thermal Properties of ECHHs
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As the thermal properties of AcGGM and AT are different, their thermal behavior yields information
about the composition of ECHHs. Therefore, thermogravimetric analysis (TGA) was utilized to
characterize thermal behavior (Fig. 6). For the conductive hydrogels, the degradation was a two-step
process. The largest weight losses for these hydrogels occurred between 210 ˚C and 400 ˚C and was
dependent on the AT contents. This was attributed to the decomposition of AcGGM and GMA. The
weight loss in the temperature range from 30 to 210 ˚C was due to desorption of incorporated water
and other low molecular weight species [40]. Although all samples were freeze-dried in the same
manner before the measurement, the water content was found to be between 2 % and 10 % for all
hydrogels. The second mass loss occurred from 400 to 600 ˚C and is assigned to the degradation of the
AT segments linked to the hydrogel network, after which the weight loss of the C1.0-
AcGGM/GMA/AT hydrogels leveled off at temperatures of approximately 600 ˚C. As expected, the
thermal stability of the hydrogels increased with increasing AT content in the hydrogel, which is most
likely due to the greater thermal stability of the AT segments [40, 41]. According to the TGA curve,
the weight loss percentages of the C1.0-AcGGM/GMA hydrogel and ECHHs in the range of 210 to
600 ˚C are WR and WH, respectively. The grafting amount of AT segments (W %) is defined by Eq.
(3), where WAT is the weight loss percentage of pure AT in the range of 210 to 600 ˚C, and W %
represents the weight percentage of the AT segment connected to the hydrogel:
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W% = ꢍ ꢄꢍꢏ × 100
ꢀ3ꢁ
ꢎ
21
ꢍ
ꢏ
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The theoretical and measured grafting amounts of AT for each hydrogel are listed in Table 3. As
anticipated, the AT contents calculated from TGA were slightly lower than the theoretical calculations
due to the incomplete reaction of AT with the epoxy groups in the hydrogel networks in the DMSO
solution.
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Fig. 6. TGA thermograms of AT and ECHHs.
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Table 3. Conductivity and composition of ECHHs.
Sample codes
Conductivity (S/cm)
AT content from TGA (theoretical)
(0%)
C1.0-AcGGM/GMA
< 10-10
C1.0-AcGGM/GMA/10%AT
C1.0-AcGGM/GMA/20%AT
C1.0-AcGGM/GMA/30%AT
(2.93±0.32)×10-8
(8.49±0.45)×10-8
(1.30±0.21)×10-7
5.2 % (10 %)
9.4 % (20 %)
18.7 % (30 %)
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3.5. Conductivity of ECHHs
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The electrical conductivities of the ECHHs with different contents of covalently attached AT were
determined after doping with an equal amount of 1 mol/L HCl via a four-probe method. The
conductivity of the hydrogel without AT was below the detector limit of the instrument (< 10-10
S/cm),which indicated the hydrogel without AT had extremely low or no conductivity. The
conductivities of the hydrogels with AT contents from 10 % (w/w) to 40 % (w/w) range from
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(2.93±0.32)×10-8 to (1.12±0.14)×10-6, respectively (Table 3). These conductivities are in the range of
what has previously been achieved [35, 42] and are adequate for the transfer of bioelectrical signals in
vivo due to the low micro-current in the body [35, 43]. It is clear that the conductivities of the
hydrogels increased with an increase in AT content, and therefore, the conductivities could be adjusted
by changing the amount of AT when formulating the hydrogels. Conventional high molecular weight
conductive polymers have many practical problems in tissue engineering applications, such as poor
polymer-cell interactions, the absence of cell interaction sites, hydrophobicity and poor solubility [25,
44]. Coupling electrically conductive AT with hydrophilic, non-toxic, degradable and soluble
hemicellulose is a promising solution to overcome the aforementioned drawbacks of previously
utilized conductive polymers.
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3.6. Swelling Behavior of ECHHs
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The swelling behavior is a key feature of hydrogels because their applications typically rely on their
ability to absorb large amounts of water in a reproducible fashion. The swelling ratio (SR) of the
hydrogels depends on the DS of C-AcGGM and the AT content (Fig. 7). Therefore, the SR could be
tuned to meet the requirements of specific applications. The DS of MA proved to have a large effect
on the swelling properties of the hydrogels (Fig. 7A). An increase in the amount of introduced MA to
AcGGM led to a decrease in hydrogel swelling. The maximum SR of the hydrogels varied as follows:
C1.0-AcGGM (DS=1.14) < C0.5-AcGGM (DS=0.60) < C0.25-AcGGM (DS=0.24). This is due to a
higher degree of cross-linking for the C1.0-AcGGM hydrogels compared to the C0.5-AcGGM
(DS=0.60) and C0.25-AcGGM (DS=0.24) hydrogels. The crosslinking density calculated from
swelling ratio is an important network parameter for composite hydrogels. The crosslinking density
ꢑ
(ꢐꢒ) was calculated according to Peppas et al. [45], Eq. (4):
ꢘ
ꢗ
ꢜꢝꢞꢟꢠꢓꢄꢘ ꢣꢤꢘ
ꢄχ
ꢘ
ꢥ
ꢡ,ꢢ
ꢛ
ꢡ,ꢢ
ꢡ,ꢢ
ꢓ
ꢕ
ꢙ
ꢚ
ꢚ
23
=
−
ꢑ
ꢔ
ꢖ
(4)
ꢧ
ꢚ/ꢦ
ꢑ
ꢡ,ꢢ
ꢡ
ꢔ
ꢊ
ꢘ
ꢄ
ꢡ,ꢢ
ꢑ
24
25
26
Here ꢐꢟ is the number-average molecular weight of the polymer chain (substituted acetyl-
galactoglucomannan); ʋ is the specific volume of the polymer, which is similar with that of dialdehyde
konjac glucomannan [46], ~0.7 cm3/g; V1 is the molar volume of the swelling medium (18.06 cm3/mol
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for water); the Flory-Huggins interaction parameter between polymer and water χ1, which is similar
with that of guar gum [47], χ1=0.4940; and the ʋ2,s is relative with swelling ratio (SR-1) [46]. The
ꢑ
3
crosslinking densities (ꢐꢒ, g/mol) of C0.25-AcGGM, C0.5-AcGGM and C1.0-AcGGM hydrogels
4
were 346, 335 and 273, respectively. The results demonstrated that the crosslinking density decreased
with the increase of the DS of MA. The decrease in crosslinking density means less space for the
accommodation of water in the network of these hydrogels, and decreases the flexibility of the
uncrosslinked polymer chain, further leading to a decrease of the SR. The C0.5-AcGGM and C0.25-
AcGGM hydrogels became softer after 48 h of swelling and did not retain their mechanical integrity as
well as the C1.0-AcGGM hydrogels. Therefore, the latter were chosen for further investigations. A
remarkable difference is seen when comparing C1.0-AcGGM/GMA with C1.0-AcGGM hydrogels.
The SR of the former (758 %) is less than half of the SR of the latter (1613 %) after 48 h of swelling.
Additionally, the swelling of C1.0-AcGGM/GMA hydrogels is much slower than that of C1.0-
AcGGM hydrogels. To clarify the effect of the hydrophilicity of the hydrogels on SR, contact angles
were measured [48]. The contact angles of C1.0-AcGGM and C1.0-AcGGM/GMA hydrogels films
were 28° and 63° (Fig. 7B). It indicated that the introduction of GMA increased the hydrophobicity of
the hydrogels, which makes difficult to adsorb water. After coupling with 10 wt. % of AT, the contact
angle of the ECHH (C1.0-AcGGM/GMA/10%AT) increased up to 75° because of the hydrophobicity
of AT, which resulted in a decrease in SR. The SR of the hydrogels containing covalently attached AT
decreased with increasing AT content due to the hydrophobicity of AT. The C1.0-AcGGM/GMA
hydrogel swelled most rapidly and had the highest SR (Fig. 7C). Compared to previous reports on
other conductive hydrogels, the SR of ECHHs in the present study with the same weight percentage of
AT are higher [31, 39]. This is most likely due to the superior hydrophilicity of AcGGM compared
with chitosan [31] and GMA-poly(Ɛ-caprolactone)-PEG-poly(Ɛ -caprolactone) [39]. Fig. 7D shows
photographs of cut pieces of C1.0-AcGGM, C1.0-AcGGM/GMA and C1.0-AcGGM/GMA/10%AT
hydrogels in dried and swollen states demonstrating the volume increase following 48 hours of
swelling.
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Fig. 7. Swelling ratios as a function of time of the different hydrogels (A and C); the water contact
angle of C1.0-AcGGM, C1.0-AcGGM/GMA and C1.0-AcGGM/GMA/10%AT hydrogels films (B),
and images of C1.0-AcGGM, C1.0-AcGGM/GMA and C1.0-AcGGM/GMA/10%AT hydrogels (D) in
the dried and swollen state (48 h of swelling).
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3.7. Morphology of The Hydrogels by Scanning Electron Microscopy (SEM)
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The morphological changes of the hydrogels before and after swelling also provide information on the
swelling behavior of the hydrogels. SEM images of a cross-section of the C1.0-AcGGM (A), C1.0-
AcGGM/GMA (B) and C1.0-AcGGM/GMA/20%AT (C) hydrogels in the dried state (A-1, B-1 and C-
1) and the swollen state (48 h) after lyophilization (A-2, B-2 and C-2) are shown in Fig. 8. Before
swelling, all hydrogels had a compact structure, while a homogenous macro-porous structure appeared
after 48 h of swelling, indicating that these hydrogels swelled in a homogenous manner. Interestingly,
the C1.0-AcGGM hydrogels had larger pores with thinner walls, which could absorb a larger amount
of water compared to the other hydrogels (C1.0-AcGGM/GMA and C1.0-AcGGM/GMA/20%AT).
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This confirms and explains the findings concerning the SR where the C1.0-AcGGM hydrogels had a
high SR of 1613 %, while the SR dropped to 758 % for C1.0-AcGGM/GMA and to 468 % for the
C1.0-AcGGM/GMA/20%AT hydrogels. It becomes increasingly difficult for the water molecules to
penetrate through the thicker walls in the hydrogels, and an increased hydrophobicity also decreases
the SR. Therefore, the swelling rate of C1.0-AcGGM hydrogels is higher than those of C1.0-
AcGGM/GMA and C1.0-AcGGM/GMA/20%AT hydrogels.
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Fig. 8. SEM images of the cross-section of C1.0-AcGGM (A), C1.0-AcGGM/GMA (B) and C1.0-
AcGGM/GMA/20%AT (C) hydrogels in the dry state (A-1, B-1 and C-1) and lyophilized from the
swollen state at 48 h (A-2, B-2 and C-2). Magnification: ×500.
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4. Conclusions
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Electrically conductive hemicellulose hydrogels (ECHHs) have been successfully synthesized by a
straight-forward and robust approach by introducing the conductive aniline tetramer (AT) into
hydrophilic, non-toxic, and biocompatible hemicellulose networks. The ECHHs were prepared in two
steps: first, carboxylated AcGGM (C-AcGGM) was dissolved with GMA followed by a
polymerization initiated by ammonium persulfate; second, the formed hydrogels were covalently
coupled with varying amounts of AT, which was homogeneously distributed throughout the network.
C-AcGGM hydrogels were synthesized with 0.25, 0.5 and 1.0 eq of maleic anhydride and had
swelling ratios (SR) of 2300 %, 2180 % and 1613 %, respectively. By increasing of the AT content,
the SRs were tuned from 548 % to 228 %, while simultaneously altering the conductivities by two
orders of magnitude. The ability to control both swelling behavior and conductivity provides a wide
range of material properties able to meet the needs of many specific applications.
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5. Acknowledgments
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The authors are grateful to the China Scholarship Council (CSC), ERC Advanced Grant, PARADIGM
(Grant Agreement No. 246776) and The Royal Institute of Technology (KTH) for financial support for
this work. Dr. Simon Leijonmarck at the Department of Applied Electrochemistry, School of
Chemical Science in KTH is thanked for the kind support in the conductivity testing. Finally, our great
appreciation goes to Professor Changsheng Zhao in Sichuan University for the generous help in
applying to the scholarship from CSC.
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