Swelling and mechanical properties of hydrogels composed of binary blends of inter-linked pH-responsive microgel particles.

View Article Online View Journal

Soft Matter Accepted Manuscript

This article can be cited before page numbers have been issued, to do this please use: A. H. Milani, B. R. Saunders, T. Freemont and J. Bramhill, Soft Matter, 2015, DOI: 10.1039/C4SM02432J.

This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains.

www.rsc.org/softmatter

Page 1 of 24

Soft Matter View Article Online

DOI: 10.1039/C4SM02432J

1

Swelling and Mechanical Properties of Hydrogels Composed of

Amir H. Milania,*, Jane Bramhillb, Anthony J. Freemontc and Brian R. Saundersa,* a

Polymer Science Research Group, School of Materials, University of Manchester, Grosvenor

Street, Manchester, M13 9PL, U.K. b

c

Gelexir Healthcare Ltd, C/o- Ward Hadaway, The Observatory, Chapel Walks, UK, M2 1HL.

Regenerative Medicine, Developmental Biomedicine Research Group, School of Medicine,

Stopford Building, University of Manchester, Oxford Road, Manchester, M13 9PT ABSTRACT We show that a new type of hydrogel can be prepared by covalently inter-linking binary blends of microgel (MG) particles and that the swelling ratio and modulus of the gels can be predicted from their composition. In previous work we established that physical gels of glycidyl methacrylate

(GMA)

functionalised

poly(methyl

methacrylate-co-methacrylic

acid-co-

ethyleneglycol dimethacrylate) microgel particles (GMA-MG) could be covalently inter-linked to give hydrogels, termed doubly crosslinked microgels, DX MGs. We build on this concept here by investigating the properties of DX MGs containing binary blends of GMA-MG particles and glycidyl oligo(ether ester) acrylate-functionalised microgel particles (GOE-MG). These new hydrogels were assembled by inter-linking nanoscale MG building blocks in the absence of small molecule monomers or crosslinkers. The volume fraction of GMA-MG particles used to prepare the GOE/GMA DX MGs was systematically varied. Rheology data showed that inclusion of GMA-MG and GOE-MG within the GOE/GMA DX MGs increased the modulus and yield strain, respectively, compared to the values measured for the respective physical gels. The data for the covalent GOE/GMA DX MG gels showed that the ductility increased with increasing GOE-MG content. GOE provided covalent inter-linking of the MG particles and also acted as a lubricant between particles due to its low Tg. By demonstrating compositionally determined swelling and mechanical properties for DX MG gels prepared using binary blends of MG particles, this study introduces a


Published on 06 February 2015. Downloaded by University of Prince Edward Island on 07/02/2015 03:15:52.

Binary Blends of Inter-linked pH-Responsive Microgel Particles

Soft Matter

Page 2 of 24 View Article Online

2

DOI: 10.1039/C4SM02432J

new, widely applicable, hydrogel construction assembly concept that is not available for conventional hydrogels.

Whilst hydrogels have attracted enormous attention in the polymer literature1-8, largely due to their potential for biomedical applications9-13, the majority of hydrogels are constructed using “bottom up” methods involving small molecule monomers14-16. Much of the interest in hydrogels has been driven by the need to transform their inherent brittle mechanical properties into ductile, tough materials17,

18

. Success has been demonstrated in achieving gels with improved toughness and

ductility using a variety of bottom up methods which include, nanocomposite hydrogels18, tetraPEG gels19, slide-ring gels20 and double network hydrogels17. In this study we use a completely different hydrogel construction method which involves inter-linking pre-formed nanoscale microgel (MG) particles. MG particles have been widely studied in the literature21-27. Because MG particles are crosslinked polymer particles that swell when the pH approaches the pKa of the constituent polyacid (or polybase) chains21, 24, 28, they are singly crosslinked. Consequently, the joining together of MG particles by covalent inter-linking to form a hydrogel constitutes double crosslinking, and we term these gels, doubly crosslinked microgels (DX MGs)29. Whilst we have investigated a wide range of DX MG homogels prepared from one type of MG29, 30, the present work greatly extends our DX MG concept by investigating DX MGs prepared from binary blends of vinyl-functionalised MGs for the first time. The hypothesis that is tested in this study is that the swelling ratio and modulus of DX MGs composed of binary MG blends should be predictable from the properties of the homogel DX MGs. The hypothesis provides considerable potential for the rational and quantitative design of hydrogel properties using bespoke nanoscale gel building blocks. Hydrogels containing MG particles have been studied in a variety of forms and have been reviewed extensively elsewhere23, 31. The key feature that distinguishes our DX MGs from all these studies is that for our approach we simply covalently link the MG particles together, after a pH-triggered particle swelling step, to form a hydrogel. The MG particles act both as the crosslinking unit and



INTRODUCTION

Page 3 of 24


DOI: 10.1039/C4SM02432J

3

also the matrix forming element31. By contrast, the earlier studies by Hu et al. relied on the presence of added small monomers to prepare linear polymer that interlinked MG particles32, 33. In a different

MG particles. Whilst the present polyacid MG particles are an order of magnitude smaller than the MG particles of Gong et al34, there is a crucial difference between their work and the DX MG study presented here. That is that their MG particles were dispersed within a continuous hydrogel network34. If their MG particles were removed a hydrogel would still remain. However, if our MGs were removed there would be nothing left. Their MG-reinforced hydrogels also relied on the bottom up approach to generate the continuous phase34, 36. The physical and mechanical properties of DX MGs prepared by doubly crosslinking poly(methyl methacrylate-co-methacrylic

acid-co-ethyleneglycol

dimethacrylate

(poly(MMA-co-MAA-co-

EGDMA)) and poly(ethylacrylate-co-MAA)-co-1,4-butanediol diacrylate) MGs that were functionalised by either glycidyl methacrylate (GMA) or 2-aminoethylmethacrylate (AEM) have been investigated by our group29, 37 and the concept extended to include doubly crosslinked GMAfunctionalised cationic poly(vinylamine) MGs30. Compared to some of the most ductile gels that have been reported17, 38, DX MGs had relatively low yield strains and were brittle due to relatively short inter-particle strands that locked particles in their positions and provided limited opportunity for movement under excessive strain. Here we invoke the general concept of using a binary blend to modulate gel mechanical properties5. However, in this study binary blends of MG particles are used. Unlike other studies involving binary blends of MG particles39, in the present work the MGs covalently interlink to form permanent gels. To achieve a method for preparation of a more ductile DX MG it was decided to replace the source of pendant vinyl groups (GMA) with glycidyl oligo(ether ester) acrylate (GOE) (see Scheme 1). We postulated that the inclusion of GOE would (a) decrease the crosslink density in the inter-linking region between neighbouring MG particles because of GOE’s longer chain length cf. GMA and (b) lower the friction at particles’ interface due to its low Tg. The preparation of new vinyl-



approach, Gong et al.34 and Richtering et al.35 extensively studied hydrogels that are reinforced by

Soft Matter


4

DOI: 10.1039/C4SM02432J

functionalised MGs enabled the opportunity to construct DX MGs from binary blends of MG particles with intrinsically different mechanical properties and this new approach was investigated

Scheme 1. Depiction of preparation of DX MG composite containing GOE and GMA MG particles.

In this study we investigate relationships between DX MG composition and mechanical properties, using swelling, dynamic rheology and static compression measurements. Because our earlier work showed potential for biomaterial application for DX GMA-MG gels40, we also introduced here a low toxicity free-radical initiator system for the preparation of these gels. The mixed initiator system, which was ammonium persulfate (APS), ascorbic acid (AS) and iron sulfate, enabled gel formation to occur at 37 oC. We stress that this study is focussed on structure-property relationships for a new hydrogel system and does not consider biomaterial applications or cytotoxicity. The latter aspects will be the subject of future publications. This study shows that the swelling ratio and modulus of the new mixed DX MGs is directly related to the volume fraction of each MG type



here.

Page 5 of 24


5

DOI: 10.1039/C4SM02432J

present. Furthermore, the DX MGs containing GOE-MG had increased ductility. The study demonstrates a versatile approach for DX MG construction using binary MG blends that should

mechanical properties by combining pre-formed MG particles using rational design.

EXPERIMENTAL SECTION Materials Methyl methacrylate (MMA, 98.5 %), methacrylic acid (MAA, 99 %), ethylene glycol dimethacrylate (EGDMA, 98 %), ammonium persulfate (APS, 98 %,), sodium dodecyl sulphate (SDS, 98.5 %), potassium phosphate dibasic trihydrate (K2HPO4.3H2O, 99 %) were purchased from Aldrich and used as received. Potassium tert-butoxide (tBuO-K+, 95 %), epibromohydrin (EBH, 98%), (±)-epichloromohydrin. (ECH, 99 %), ferrous sulfate heptahydrate (FeSO4.7H2O, 98 %) were also purchased from Aldrich and used as received. 2-Hydroxyethyl acrylate (HEA, 97 %) was purchased from Alfa Aesar. Chloroform and hexane were purchased from Fisher and used as received. L-Ascorbic acid (AS, 99 %) was purchased from Scientific Laboratory Supplies Ltd and used as received. Doubly-distilled deionised water was used in all experiments.

Oligoether-ester acrylate synthesis Hydroxyl oligo(ether ester) acrylate (HOE) was synthesised using the method of Gibas et al.41 Dried HEA (25 g, 0.215 mole) was added to a 150 ml flask and stirred magnetically while purging with argon. After 10 minutes, tBuO-K+ (1.0 g, 8.9 mmole) was added and left for 1 h at room temperature. The reaction was stopped by adding HCl (0.5 M, 50 ml) and the product extracted using chloroform. The product was washed thoroughly with hexane to remove unreacted monomer and by-products.

Glycidylised oligoether-ester acrylate synthesis HOE was glycidylised to give GOE using a mixture of ECH and EBH in the presence of KOH. HOE (14 g, 17.2 mmole) and ECH (160 ml, 2.0 mole) and EBH (25 ml, 0.30 mole) were added to a



have excellent potential for construction of future hydrogels with pre-determined swelling and

Soft Matter


6

DOI: 10.1039/C4SM02432J

250 ml flask and stirred magnetically. To this solution, solid KOH (1 g, 17.9 mmole) was added and then reaction mixture was left for 48 h at room temperature. Excess ECH and EBH was removed by

product was also washed with hexane thoroughly until full removal of residual ECH and EBH and then dried under vacuum. HOE and GOE were characterised using 1H NMR and GPC (Fig. S1) and the details are given in the Supporting Information. The value for the number of repeat units for GOE was 7.0 (Scheme 1).

Precursor microgel synthesis Singly crosslinked MG was prepared using a modification to previous studies40. Briefly, SDS (1.6 g, 5.5 mmole) was dissolved in water (517.0 g) and added to a one litre 4 necked-round-bottomed flask with overhead stirrer. This solution was purged by nitrogen for 30 min while the temperature increased to 80 °C. A monomer solution was prepared containing MMA (186.0 g, 1.86 mole), MAA (98.0 g, 1.14 mole) and EGDMA (1.0 g, 5.0 mmole). A total of 16.0 g of the monomer solution was added to reaction vessel as a seed and left to stir for 5 min, after which time K2HPO4 (0.17 g, 0.98 mmole) and APS (0.07 g, 0.31 mmole) were added. After 30 min the remaining monomer and water (150 g) were added with rate of 1 ml/min. After the feed, the reaction was left for another 1 h and quenched with ice. The product was extensively dialysed against water. These MG particles had a number-average diameter of 77 nm determined by SEM and a hydrodynamic diameter at pH = 4 of 89 nm.

Microgels functionalised with glycidyl methacrylate or glycidylised oligoether-ester acrylate The method used for preparation of GMA-MG was described earlier40. Briefly, GMA (16.66 g, 0.117 mole) was reacted with MG dispersed in water (100 g of 10 wt.% dispersion) at a pH of ~ 3.5 and a temperature of 50 °C for 18 h. The particles were washed extensively with chloroform and separated using water washing. GOE-MG was prepared using the following method: GOE (3.3 g, 3.35 mmole) was mixed with 80 g of 5 wt% MG dispersion (above) and allowed to stir for 20 h at 40°C. The product was washed with chloroform and then extensively dialysed.



rotary evaporator and the crude product was washed with water and extracted with chloroform. The

Page 7 of 24


DOI: 10.1039/C4SM02432J

7

Doubly crosslinked microgel synthesis GMA DX MG, GOE DX MG and mixed GOE/GMA DX MG gels were prepared by mixing two

(0.76 g of 18 wt % dispersion) or GOE-MG (0.76g, 18 wt %), AS (0.1 M, 0.004 mmole), and FeSO4 (0.1 M solution, 0.0015 mmole) while mixture B was composed of NaOH (2 M, 0.2 mole) and APS (0.2 M solution, 0.005 mmole). The compositions and names used for the gels are given in Table 1. The value for ΦGMA represents the volume fraction of GMA-MG particles within the gels in the dry state. For GOE0.25-GMA0.75 (Φ GMA = 0.75) the binary mixed dispersion used to prepare the gel contained 75 vol. % GMA-MG and 25 vol.% GOE-MG on a dry weight basis. Here, mixture A comprised GMA-MG (1.20 g, 22.9 wt%), GOE-MG (0.60 g, 16.4 wt%), AS (0.160 ml, 0.1 M) and FeSO4 (0.060 ml, 0.1 M) while mixture B contained NaOH (0.31 ml, 2 M), APS (0.10 ml, 0.2 M) and water (0.145 ml). Hybrid samples with other ratios were prepared (Table 1) using the proper ratios of GOE-MG to GMA-MG. Samples for rheology testing were doubly crosslinked by mixing in a vial and placing them in an O-ring confined with two glass slides. Samples for compression test were prepared using Medmix double chamber syringe (4:1). Double crosslinking was conducted at 37°C overnight. All gels had a (hard sphere) volume fraction of 0.12 and pH of 7.4 - 7.6. a

Table 1. Characterisation data for the DX MGs

preparation state

ΦGMAb

name

0

c

after 3 days swelling

φGOE(hs)

φGMA(hs)

φo(hs)

φ(hs)

Q

GOE1.0-GMA0

0.121

0

0.121

0.050

20.0

0.25

GOE0.75-GMA0.25

0.089

0.032

0.121

0.053

19.0

0.50

GOE0.50-GMA0.50

0.060

0.060

0.121

0.071

14.0

0.75

GOE0.25-GMA0.75

0.032

0.089

0.121

0.078

12.9

1.0

GOE0-GMA1.0

0

0.0121

0.121

0.087

11.4

a

The subscript hs refers to the hard sphere volume fraction assuming that all of the MG particles were fully collapsed. b Volume fraction of MG in the composite in the dry state. c The subscripts refer to the volume fractions of each MG (GOE-MG or GMA-MG) in the binary gel in the dry state.

Physical measurements 1

H NMR spectra were obtained using a Bruker 400 MHz instrument. The solvent used was CDCl3.



mixtures of A and B. For GMA DX MG and GOE DX MG, mixture A comprised either GMA-MG

Soft Matter


8

DOI: 10.1039/C4SM02432J

GPC was performed using a system equipped with a Shodex RI-101B refractive index detector at 35 °C. THF was used as eluent. Samples were dissolved at ~ 0.2 % (w/v) in THF prior to injection.

Titration measurements were performed using a Mettler Toledo titration unit in the presence of aqueous NaCl (0.1 M). Photon correlation spectroscopy (PCS) measurements were performed using a BI-9000 Brookhaven light scattering apparatus (Brookhaven Instrument Corporation), fitted with a 20 mW HeNe laser and the detector which was set at a scattering angle of 90°. The volume swelling ratio (Q) of particles was calculated using equation 1: ௗ೓

ܳ = ൬ௗ

೓(ర)

൰

ଷ

(1)

where dh and dh(4) are the hydrodynamic diameters of particles in the swollen and collapsed states (at pH = 4), respectively. The latter assumption is supported by the similarity of the values of dh(4) and the number-average diameters determined from SEM (later). The SEM measurements were obtained using a Philips FEGSEM instrument. At least 100 particles were measured to determine the number-average SEM diameters. The swelling behaviour of DXMG in buffer was studied using a gravimetric method. Samples were placed in containers, which were filled with buffer (0.1 M, pH = 7.4), for 8 days. Samples were weighed once a day and the buffer refreshed. The soluble fraction (SF) was obtained by drying samples used for the swelling tests at 80°C for 48 hours. The volume swelling ratio (Q) for the gels was calculated using: ொ(೘)

ܳ = ߩ௣ ൬

ఘೞ

ଵ

ఘ೛

+ఘ ൰− ఘ ೛

ೞ

(2)

where Q(m) is the ratio of the swollen gel mass to the dry mass. The parameters ρs and ρp are the densities of the solvent and polymer, respectively. These were taken as 1.0 and 1.2 g cm-3.



The system was calibrated with poly(methyl methacrylate) (PMMA) standards.

Page 9 of 24


9

DOI: 10.1039/C4SM02432J

Dynamic rheology measurements were performed using a TA Instruments AR G2 temperaturecontrolled rheometer which was equipped with an environmental chamber. A 20 mm diameter plate

1 Hz. A strain of 1 % was used for the frequency sweep measurements. These data provided the storage (G’) and loss (G”) modulus. Unless otherwise stated rheological data presented in this study were measured for the DX MGs, i.e., the covalent interlinked gels. Compression measurements were performed using an Instron at a compression rate of 0.5 mm / min. Samples had a cylindrical geometry with diameter of 10 mm and height of 6 mm. Young’s modulus values were calculated from the initial gradient of stress-strain curve at strains (ε) of less than 10%. Cyclic strain loadingunloading experiments were conducted at a rate of 0.5 mm/min. Data are also shown in terms of the extension ratio λ (= 1 - ε).

RESULTS AND DISCUSSION Microgel characterisation The method used for vinyl-functionalising the MGs involved epoxide ring-opening through reaction with RCOOH groups (Scheme 1). The same parent MG particles were used to prepare the GOEMG and GMA-MG particles in this study. SEM was used to verify the spherical morphology of the GOE-MG (Fig. 1a) and GMA-MG particles (Fig. 1b), determine the number-average diameters (DSEM) and determine the size polydispersities. The DSEM diameters were in the range of 77 – 81 nm and were not significantly different from the value of 77 nm determined for the parent SX MG particles. The coefficient’s of variation were in the range of 15 – 17 % and are consistent with earlier reports29, 40.



geometry was used. The gap used was 2500 µm. For strain sweep measurements the frequency was

Soft Matter


DOI: 10.1039/C4SM02432J

Fig. 1. Vinyl-functionalised microgel particle characterisation. SEM images of GOE-MG (a) and GMA-MG (b). Variation of (c) hydrodynamic diameter and (d) volume swelling ratio with pH for the MGs.

To determine the extent of functionalisation, either with GMA or GOE, the RCOOH contents were determined before and after functionalisation using potentiometric titration data (see Fig. S2). The parent non-functionalised MG had a MAA content of 33.5 wt.%. The decrease in MAA content was least when the MG particles were functionalised with GOE (Table 2). GOE is a relatively large molecule compared to GMA (Scheme 1), and is proposed to have penetrated less deeply within the MG particle shell and reacted with fewer RCOOH groups. Additionally, GOE has a hydrophobic chain and is collapsed in aqueous dispersion, so there was a higher possibility that the epoxide end was hindered and less able to react with RCOOH groups. The GOE content corresponded to 17.5 wt.% of the GOE-MG particles and is believed to have been present near the particle periphery. It is stressed that the rigorous washing procedure, which used chloroform (Experimental Section), removed residual HOE leaving only covalently linked GOE attached to the GOE-MG particles.



10

Page 11 of 24


DOI: 10.1039/C4SM02432J

11

Table 2. Characterisation data for the vinyl-functionalised microgel particles GMA or GOE e / mol.%

Microgel

DSEM / nma

dh(4) b / nm

dh(7.4) b / nm

Qc

pKa d

MAA / wt.%

GOE-MG

81 [ 17]

95 ± 4.8

204 ± 10

10.0 ± 1.5

6.6 ± 0.1

26.1 ± 0.4

4.6 ± 0.1

GMA-MG

77 [ 15]

90 ± 4.5

277 ± 14

29.2 ± 4.4

6.5 ± 0.1

24.1 ± 0.4

17.9 ± 0.6

Number-average SEM diameter of collapsed particles. The coefficient of variation (= 100 x std. dev / mean) is shown in brackets. b Hydrodynamic diameter measured by PCS. c Swelling ratio determined from the hydrodynamic diameters and equation 1 at pH = 7.4. d Apparent pKa. e Mol.% of MAA groups originally present that reacted as determined from potentiometric titration data (Fig. S2).

The GOE-MG and GMA-MG particles swelled when the pH was increased beyond the pKa values (Fig. 1c and d). The GOE-MG particles had lower Q values than the GMA-MG particles. The swelling of a polyelectrolyte MG particle is governed by interactions that favour swelling (solvent mixing and dilution of mobile ions) and the elastically effective chains that oppose swelling24. The MAA contents were comparable for GOE-MG and GMA-MG (Table 2) ruling out significant differences in mobile ion concentration as a cause for the Q differences at higher pH (Fig. 1d). Incorporation of GOE within the GOE-MG particles increased the extent of hydrophobicity of the particles and most likely provided an additional source of hydrophobic attractive interactions. The latter interactions are well known to oppose pH-triggered swelling of MGs42.

Mixed DX MG gel preparation and swelling behaviours DX MGs were prepared using either GOE-MG or GMA-MG (homogels) or mixtures of both MG types (binary gels). Blending of the two MG types provides the opportunity to modify the crosslinking of the gels at the scale of the MG particles (~ 200 – 300 nm). The DX MG binary blends were prepared by a pH-triggered fluid-to-gel transition using well mixed MG dispersions. Rapid formation of the physical gel should have prevented segregation of the two MG types present. Consequently, we propose that the identity of the nearest neighbours of each MG particle within the binary gels was statistically determined by the proportions of each MG type present. Furthermore, it is likely that there was considerable disorder within the gels with some free space between the particles which depended on the local particle packing that was present when the MG particles swelled and were kinetically trapped (frozen) in their local particle arrangements prior to final permanent covalent interlinking.



a

Soft Matter


12

DOI: 10.1039/C4SM02432J

Although in this study it is the nature of the inter-linking at the MG particle interfaces that was varied, the general mixing approach that we introduce here for the first time would apply to gels

sphere volume fraction values and not the calculated effective volume fractions (φeff) occupied by the MG particles. Values for φeff have been reported for several studies43, 44 based on dilute solution viscosity data. However, values for φeff obtained from such data have been reported as not being entirely accurate in the range of 0.35 to 0.75 and are expected to diverge rapidly at higher values45. Moreover, it would not be possible to obtain separate φeff values for each of the MG types within binary MG dispersions considered here using dilute solution viscosity measurements. Thaiboonrod et al. estimated φeff values directly from optical micrographs for large, micrometer-sized, MGs30. Unfortunately, the MGs in the present study were too small to be visualised by optical microscopy. Given the factors discussed above hard sphere volume fractions were used for this study.

The swelling behaviour of the new DX MGs was studied by measuring Q at pH = 7.4 (Fig. 2a). All of the gels showed an initial increase in Q upon immersion into the PBS (0.1 M) solution. The equilibrium swelling ratio of polyelectrolyte gels is governed by a balance between absorption of water due to mixing with network chains as well as the dilution of mobile ions within the network and the elastically effective chains which oppose network expansion46, 47. Each of the gels showed an initial increase in Q over the first 1 day. This increase is due to ingress of water and is driven by mixing and mobile ion dilution and has been reported for other gels47. After the Q maximum was reached for GOE1.0-GMA0, GOE0.75-GMA0.25 and GOE0.5-GMA0.5, a subsequent decrease occurred. This decrease is probably due to a minor mass reduction that occurred for these gels as determined by the soluble fraction data (Fig. 2b). It is emphasised that none of the DX MGs or composites redispersed during these experiments which confirms that inter-microgel particle crosslinking occurred in all cases. By contrast, the parent physical gels spontaneously redispersed when placed in water.



containing different vinyl-functionalised MGs. Our binary DX MGs are discussed in terms of hard

Page 13 of 24


DOI: 10.1039/C4SM02432J

13

25

15

Q

Q


15

0.1

10

10

0 0.25 0.5 0.75 1

5 0 0

1

2

3 4 5 Time / d

6

7

8

5 00 -0.2 0.0

(b)

0.0

0.2

0.4

0.6

0.8

1.0

1.2

ΦGMA

Fig. 2. Swelling ratio of DXMGs. (a) Variation of swelling ratio (Q) with time for different gels. The legend shows the volume fraction of GMA-MG particles in the dry state (ΦGMA) for each gel. (b) Swelling ratio and soluble fraction (SF) as a function of ΦGMA. The SF value for GOE1.0-GMA0 could not be measured because of fragmentation. The Q and SF values were measured after 3 and 8 days, respectively. The red line shows calculated Q values from Equation 4.

To enable the effect of composition to be studied the Q values measured after 3 days were plotted (Fig. 2b). We first compare Q values from the MG particles and homo DX MGs. We assume that MG particles within a homo DX MG have the same Q value as the gel. Importantly, the Q values for the GOE1.0-GMA0 (ΦGMA = 0) and GOE0-GMA1.0 (ΦGMA = 1.0) DX homogels are very different compared to those for the parent GOE-MG and GME MG particles at the same pH (Table 2). The differences for the Q values for the homo DX MGs and the respective MG particles are so large that they cannot be attributed to differences in the measurement methods used. In contrast to the parent MG particles, the swelling extent for DX MGs is dependent upon inter-particle and intra-particle crosslinking. Upon gel formation and subsequent swelling the Q values for the GOE-MG and GMA-MG particles increased and decreased, respectively, within the GOE1.0-GMA0 and GOE0GMA1.0 gels. These changes are attributed to a lower extent of inter-particle crosslinking within GOE1.0-GMA0 and a greater extent of inter-particle crosslinking within GOE0-GMA1.0, which follows from the higher extent of vinyl group functionalisation for GMA MGs (Table 2). We next compare Q values for the two homo DX MGs. The Q for GOE1.0-GMA0 (Φ GMA = 0) was much higher than that for GOE0-GMA1.0 (ΦGMA = 1.0) (Fig. 2b). For the DX MGs the MAA contents of the constituent MG particles were similar and the pH used (7.4) was well above the


20

Soluble fraction

0.2 Q Qcal SF

20

Soft Matter


DOI: 10.1039/C4SM02432J

14

respective pKa values (Table 2) and it follows that the MG particles were fully ionised and the driving force for water absorption were similar. Consequently, the Q differences originate from the

Because the DX MGs comprised random binary mixtures of MG particles it was postulated that the

Q values (Fig. 2) would be determined by a volume-fraction weighted summation of the Q values for the MG particles for the respective homo DX MGs. This simple, and potentially widely applicable, hypothesis was tested using the following equations.

ܳ = ߔீைா ܳீைா,଴ + ߔீெ஺ ܳீெ஺,଴ ܳ = ܳீைா,଴ + ߔீெ஺ (ܳீெ஺,଴ − ܳீைா,଴ )

(3) (4)

For the above equations, QGMA,0 (= 11.5) and QGOE,0 (= 20.0) are the swelling ratios for GOE0GMA1.0 and GOE1.0-GMA0 gels, respectively. Equation 4 followed from ΦGMA + ΦGMA = 1.0. Fig. 2b shows that Q decreased with increasing Φ GMA. This decrease in Q is due to the increase of the global number-density of elastically effective chains (νe) within the gels due to the increased proportion of the more highly crosslinked GMA MG particles. The Q values used for equations (3) and (4) were measured after 3 days and could not be corrected for possible mass loss because the SF values were not available until 8 days. The Q values after 3 days were not significantly different from the maximum values (Fig. 2a) which implies that the mass loss over that period was insignificant. Equation 4 provided a good fit to the experimental data for the binary mixtures (Fig. 2b). It follows that after 3 days of swelling the Q values for each of the component MGs within the composite gels were effectively the same as those within the pure homo DX MG gels. These results support our hypothesis regarding Q summation and suggest that it is straightforward to mix MG particles within DX MGs to achieve specific Q values. This useful design rule should provide good versatility for future application of composite DX MGs.



higher inter-particle crosslinking density present within GOE0-GMA1.0.

Page 15 of 24


DOI: 10.1039/C4SM02432J

15

Mixed DX MG gels studied by dynamic rheology The frequency dependence for G’ and G” was measured for the GOE/GMA DX MGs using a range

= 0.1 to 10 s-1). The rate of change for G’ with frequency decreased as ΦGMA increased. 100

1 0.25

ΦGMA = 0

0.50

0.75

1.0

0.1 0.1

(a)

1

10

0.1

1

10

0.1

ω /2π (s-1)

ω /2π (s-1)

1

10

0.1

ω /2π (s-1)

1

10 0.1

1

ω /2π (s-1)

10

ω /2π (s-1)

1.0

ΦGMA = 0

0.25

1.0

0.75

0.50

0.5

0.0 0.1

1

10

0.1

ω /2π (s-1)

(b)

1

10

0.1

1

10

0.1

ω /2π (s-1)

ω /2π (s-1)

1

6

G' / kPa

60

G' / kPa

10

Physical gel

Chemical gel

40 20

(c)

1

ω /2π (s-1)

8

80

00 -0.2 0.0

10 0.1

ω /2π (s-1)

4 2

0.2

0.4

0.6

ΦGMA

0.8

1.0

1.2

00 -0.20 0.00

(d)

0.20

0.40

0.60

0.80

1.00

1.20

ΦGMA

Fig. 3. Gel mechanical properties studied by frequency-sweep dynamic rheology. (a) shows dynamic storage (G’, closed symbols) and loss (G”, open symbols) against frequency measured using different ΦGMA values (shown). The yaxis scale is the same for all of the graphs. (b) shows the variation of tanδ with frequency. High frequency storage modulus (G’) data as a function of ΦGMA are shown for (a) GOE/GMA DX MGs and (b) GOE/GMA physical gels.

The ΦGMA dependence of tanδ for various frequencies showed interesting trends in that all the tanδ values decreased with increasing ΦGMA. The GOE1.0-GMA0 showed the maximum frequency dependence which is comparable to viscoelastic behaviour of entangled networks. This can be due to long interlinking chains which allows particles to move with higher degree of freedom and dissipate energy at long time scales (i.e. low frequencies); and hence they showed lower elasticity at


G', G" (kPa)

10

tanδ


of Φ GMA values (Fig. 3a). Both G’ and G” increased with strain rate over the accessible range (ω /2π

Soft Matter


16

DOI: 10.1039/C4SM02432J

low frequencies (Fig. 3a&b). GOE0.75-GMA0.25 is the gel studied with a composition closest to that at which the tanδ values first became frequency independent. The GOE/GMA gels with higher

The dependence of G’ on ΦGMA for the GOE/GMA gels at the highest frequency probed (ω /2π = 10 s-1) is shown in Fig. 3c. The values of G’ for the GOE/GMA gels containing Φ GMA < 0.50 were shear rate dependent, had not reached a frequency plateau (Fig. 3a) and cannot be considered as equilibrium values. Consequently, a quantitative analysis of their values and relationship to ΦGMA is not provided. The G’ increase with Φ GMA is due to the increased number-density of elastically effective chains afforded by the GMA-MG particles. Static compression data provided equilibrium Young’s modulus values and are explored in the context of gel composition later. Frequency-sweep dynamic rheology data for the parent GOE/GMA physical gels were also measured and appear in Fig. S3. Those data show that the frequency dependence of G’ generally increased with increasing ΦGMA and the tanδ values were almost frequency independent. Values for

G’ measured at 10 Hz are shown in Fig. 3d. It can be seen that for all the gels (with the exception of GOE1.0-GMA0) the G’ values were much higher for the DX MGs. Consequently, including GMAMGs within the GOE/GMA DX MGs increased the stiffness compared to the respective parent GOE/GMA physical gels. The yielding response of the GOE/GMA gels was investigated using large-amplitude dynamic rheology experiments (Fig. 4a). The gels all exhibited linear viscoelastic behaviours for strains (γ) less than ~ 10%. When the strain exceeded 10% the response of the gels depended markedly on

ΦGMA. For GOE0-GMA1.0, GOE0.25-GMA0.75 and GOE0.50-GMA0.50 the gels yielded with a decrease of G’ and an initial increase of G”. These values crossed over (i.e., G’ = G” and tanδ = 1) at the critical strain value, γ*. In the cases of GOE0.75-GMA0.25 and GOE1.0-GMA0 the G” increase was less pronounced (below).



ΦGMA are considered to have well developed, mostly elastic, inter-linked MG networks.

Page 17 of 24


DOI: 10.1039/C4SM02432J

17

1 0.75 0.5 0.25 0

1 0.1

(a)

10 γ /%

1

1000

(b)

10

100

γ /%

1000

10

DX MG

γ*/%

Physical gel

100

5

00 -0.5

10 0.0

(c)

0.5

ΦGMA

1.0

0

(d)

0.5

1

ΦGMA

Fig. 4 Gel stress dissipation and yielding studied by strain-sweep dynamic rheology. (a) shows dynamic storage (G’, closed symbols) and loss (G”, open symbols) against strain (γ) measured using different ΦGMA values (shown). (b) Expanded view of G” values normalised to the lowest G” value in the linear viscoelastic region for different ΦGMA values (shown). (c) shows the dependence of the normalised G” peak-to-minimum separations from (b) with ΦGMA (See text). (d) Dependence of critical strain (γ*) on ΦGMA for both covalent and physical gels.

Following the deconvolution procedure of Shao et al.48 the relative changes for G” are plotted as

G”/G”o as function of strain (Fig. 4b), where G”o is the lowest G” value from the linear viscoelastic region. A single maximum is only present for the gels containing Φ GMA > 0.50 and is attributed to (dynamic) strain-induced dissipation associated with network breakdown49. The maximum moves to higher strains with decreasing ΦGMA because there is more distance required for the particles to move to cause network breakdown in the gels that have longer crosslinking chains between the constituent MG particles. It is striking that the G”/G”o maximum associated with network breakdown was barely evident for the gels with lowest ΦGMA, i.e. GOE0.75-GMA0.25 and GOE1.0-GMA0. This result is attributed to the decrease of direct GMA-MG to GMA-MG particle linkages. The GOE-MG to GOE-MG linkages are more flexible and spread the dissipation over a much larger length scale, leading to major broadening of the maximum and also a change in energy


G', G" (kPa)

1

0.1

∆G"n


10

10

G" / G"o

1 0.75 0.5 0.25 0 1 0.75 0.5 0.25

100

Soft Matter


DOI: 10.1039/C4SM02432J

18

dissipation mechanism. The variations of ∆G”n (= (G”peak – G”o)/G”o) and γ* are plotted as a function of ΦGMA in Fig. 4c

∆G”n is a normalised measure of the extent of strain dissipation. The γ* and ∆G”n data show opposite behaviours in that the gels with the highest γ* values (Φ GMA = 0 and 0.25) had the lowest

∆G”n values and vice-versa. The inclusion of GOE-MGs strongly altered the strain-triggered network breakdown and enabled less destructive, more distributed, (dynamic) stress dissipation. Strain-sweep dynamic rheology data were also obtained for the physical gels and are shown in Fig. S4. The data showed G” maxima for physical gels prepared using ΦGMA values less than or equal to 0.50; whereas, they were largely absent for the gels with ΦGMA values greater than or equal to 0.75. There was more dissipation for the GOE-rich physical gels which is opposite to the behaviour that was apparent for the DX MGs discussed above. It follows that different gel breakdown mechanisms applied for the DX MGs and the parent physical gels. Values for γ* obtained from the strain-sweep data appear in Fig. 4d. When compared to the (covalent) DX MGs it can be seen that the γ* values were significantly larger for the DX MGs with the exception of the ΦGMA = 1.0 gel. (Higher γ* values for DX MGs compared to physical gels were also reported in our previous work for related systems29.) These results show that for the GOE/GMA DX MGs with ΦGMA values less than or equal to 0.75 double crosslinking increased γ*. Consequently, including GOE-MGs within the DX MGs increased the ductility compared to the respective parent physical gels.

Mixed DX MG gels studied by uniaxial compression measurements Whilst uniaxial tensile studies of MG reinforced gels have provided important mechanistic information concerning anisotropic fracture mechanisms34,

36

the present study was restricted to

uniaxial compression data. The latter data are well suited for probing structure-elasticity relationships and have greater fundamental and practical implications in the context of using mixed



and d, respectively. The values of G”peak is the maximum G” value for each data set. The value for

Page 19 of 24


19

DOI: 10.1039/C4SM02432J

DX MGs in the future for load support of degenerated intervertebral discs40. Uniaxial tension measurements for the gels studied here are planned for future work.

and all of the gels showed strain hardening behaviours. The ductility of the gels increased with decreasing ΦGMA. The GOE1.0-GMA0 gel was very ductile and fracture did not occur over the experimental extension ratio range. This gel had a compressive extension ratio at break of less than 0.17 (or a maximum yield strain, εmax, greater than 83%) and a maximum true stress (σT(max)) of greater than 286 kPa. As shown in Fig. 5b it is clear that both εmax and σT(max) decreased as ΦGMA increased. These effects are due to GOE, which increased gel ductility through modulation of the strain-induced rupture of inter-MG linkages.

Fig. 5. Gel mechanical properties determined from uniaxial compression measurements. (a) Curves of true stress (σT) as a function of extension ratio (λ) for a range of ΦGMA values. (b) Variation of the maximum strain (εmax) and maximum true stress (σT(max)) as a function of ΦGMA. (c) shows Voigt–Morris model fitting for Young’s modulus (E) of GOE/GMA hydrogels. E data are shown as a function of ΦMG (black diamonds). The blue dashed line represents theoretical values (see text). In all cases the total polymer volume fraction was 0.12.

The GOE/GMA DX MGs comprised randomly arranged GOE and GMA MG particles that were interconnected. To better describe the modulus variation the Voigt50 model and Morris51 isostrain model were applied. The Voigt model envisages two components that are parallel to the applied strain. The isostrain model envisages a soft material dispersed within a continuous phase of a hard material. Whilst the origins of these two models have differences each has features that match our view of these mixed binary DX MGs (discussed above). Both of these models give equivalent expressions for the modulus of a binary composite containing different modulus components. The



Compression stress-strain measurements were conducted using the GOE/GMA DX MGs (Fig. 5a)

Soft Matter


DOI: 10.1039/C4SM02432J

20

‫ீߔ = ܧ‬ைா ‫ீܧ‬ைா,଴ + ߔீெ஺ ‫ீܧ‬ெ஺,଴

(5)

‫ீܧ = ܧ‬ைா,଴ + ߔீெ஺ ൫‫ீܧ‬ெ஺,଴ − ‫ீܧ‬ைா,଴ ൯

(6)

EGOE,0 and EGMA,0 are the modulus values of the GOE1.0-GMA0 and GOE0-GMA1.0 gels, respectively. In deriving equation 5 it was assumed that QGMA = QGOE within each as prepared hydrogel and that the densities of the GMA and GOE polymers comprising the microgels were the same. The former assumption was made to simplify the analysis and is reasonable because the total polymer volume fraction within all the as made gels was the same (0.12). After inserting the values for EGOE,0 (1.5 kPa) and EGMA,0 (74.1 kPa) into equation 6, the calculated values in Fig. 5c (dashed blue line) were obtained. The good fit to the experimental data shows that the composite models of Voigt and Morris provide a quantitative description of the modulus variation with composition for GOE/GMA DX MGs. This result shows that the modulus for these gels can be easily tuned and predicted through composition variation. The rational design of future DX MGs with tailored mechanical properties through control of the structures of the component binary (or ternary etc.) MG particles would seem to be feasible based on these results and equation 6. Energy dissipation is an important property of gels as it opposes crack formation and increases ductility52. We probed the static dissipation mechanism using slow strain-controlled loadingunloading cycles (Fig. 6a). The maximum strain for each sample was chosen to be half of the εmax values (Fig. 5b). In each case hysteresis loops were present and the initial sample height was not recovered over the duration of the unloading stage (4.5 min). The extent of hysteresis decreased as

ΦGMA increased. The dissipation energy is the area within the stress-strain loop52 and was normalised by the compression energy of the respective loading cycle and the data appear in Fig. 6b. The dissipative capability prior to gel rupture increased with decreasing ΦGMA and was highest for GOE1.0-GMA0 gel. This gel also reached the smallest λ value (Fig. 5a) and had the highest γ*



following equations were obtained.

Page 21 of 24


21

DOI: 10.1039/C4SM02432J

value (Fig. 4d) showing that the there is a strong link between normalised static dissipation energy and ductility for these gels. In addition to covalent linkages, energy dissipation for the GOE-rich

Fig. 6. Dissipation and recovery studies. (a) Effect of ΦGMA on the first loading-unloading compression cycle (see text). (b) ΦGMA dependence of the normalised dissipated energy, which is the ratio of the area under the loops in (a) normalised by the strain energy of the respective loading cycle. The inset in (b) shows GOE0-GMA1.0 before and after compression. The brown colour of the gel is due to the use of FeSO4 as an accelerator.

Conclusions We have investigated a new type of composite gel constructed by covalently “stitching together” pre-prepared colloidal gel particles that provide different elastically effective chain contributions to the gel. The contributions to network elasticity were pre-determined by MG particle design and controlled by binary DX MG composition. This approach to structure-property control is not possible for conventional gels which are constructed from the bottom up using small molecule monomers and crosslinkers. Uniquely, the double crosslinking method introduced here has enabled construction of hydrogels using nanoscale building blocks without any other additive (e.g., small monomers). In contrast to other work34, the MG particles used here act as both the crosslinker and matrix. Here, we functionalised pH-responsive MG particles with GMA and also a new oligomer, GOE and investigated the properties of the homo and binary DX MG gels. It was shown that the swelling ratios of the binary gels could be predicted simply from the volume fractions of each MG type present within the DX MGs and this implied that each MG type retained its intrinsic swelling properties with the binary gels. The use of GOE-MGs provided gels with enhanced ductility and this was attributed to a combination of providing higher degree of freedom for particles and also



gels is proposed to involve plasticising effect of (hydrophobic) GOE chains as well.

Soft Matter


22

DOI: 10.1039/C4SM02432J

reducing interfacial friction at particle-particle interface. When compared to the parent physical gels the G’ or γ* values for the DX MGs increased, respectively, with volume fraction of GMA-MG or

the stiffness and ductility. The latter behaviour is unusual for gels. Static compression measurements of the DX MGs showed that the modulus of the binary gels could also be predicted from a simple composition based equation that was analogous to that used for the swelling ratios. Furthermore, cyclic compression measurements revealed that energy dissipation was greatest for the GOE-MG rich gels, which also had the highest εmax values. The results of this study show that the key gel properties of hydrogels (swelling and modulus) can be predicted for these new binary DX MG gels. There is very good reason to believe that a wide range of swelling and elasticity behaviour could be achieved by applying the simple composition based design rules (equations 4 and 6) established in this study to a wide range of binary (or ternary etc.) DX MGs in future. Acknowledgements The authors gratefully acknowledge UMIP and the University of Manchester for funding.

References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

Y. Akagi, J. P. Gong, U.-i. Chung, and T. Sakai. Macromolecules 2013, 46, 1035-1040. M. Arifuzzaman, Z. L. Wu, R. Takahashi, T. Kurokawa, T. Nakajima, and J. P. Gong. Macromolecules 2013, 46, 9083-9090. O. E. Philippova, A. M. Rumyantsev, E. Y. Kramarenko, and A. R. Khokhlov. Macromolecules 2013, 46, 9359-9367. Q. Chen, L. Zhu, L. Huang, H. Chen, K. Xu, Y. Tan, P. Wang, and J. Zheng. Macromolecules 2014, 47, 2140-2148. J.-U. Sommer, R. Dockhorn, P. B. Welzel, U. Freudenberg, and C. Werner. Macromolecules 2011, 44, 981-986. J. A. Yoon, T. Kowalewski, and K. Matyjaszewski. Macromolecules 2011, 44, 2261-2268. T. L. Sun, T. Kurokawa, S. Kuroda, A. B. Ihsan, T. Akasaki, K. Sato, M. A. Haque, T. Nakajima, and J. P. Gong. Nat Mater 2013, 12, 932-937. J. H. Lee, J. Ahn, M. Masuda, J. Jaworski, and J. H. Jung. Langmuir 2013, 29, 13535-13541. H. Cui, Y. Liu, Y. Cheng, Z. Zhang, P. Zhang, X. Chen, and Y. Wei. Biomacromolecules 2014, 15, 11151123. J. Cui, M. A. Lackey, A. E. Madkour, E. M. Saffer, D. M. Griffin, S. R. Bhatia, A. J. Crosby, and G. N. Tew. Biomacromolecules 2012, 13, 584-588. Z. Lin, S. Cao, X. Chen, W. Wu, and J. Li. Biomacromolecules 2013, 14, 2206-2214. K. A. Mosiewicz, L. Kolb, A. J. van der Vlies, M. M. Martino, P. S. Lienemann, J. A. Hubbell, M. Ehrbar, and M. P. Lutolf. Nat Mater 2013, 12, 1072-1078. M. W. Tibbitt, A. M. Kloxin, L. A. Sawicki, and K. S. Anseth. Macromolecules 2013, 46, 2785-2792. T. Aoki, M. Kawashima, H. Katono, K. Sanui, N. Ogata, T. Okano, and Y. Sakurai. Macromolecules



GOE-MG. Accordingly, introducing covalent linkages (between the MG particles) increased both

Page 23 of 24



15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52.

DOI: 10.1039/C4SM02432J

1994, 27, 947. N. A. Peppas (1986) Hydrogels in medicine and pharmacy, CRC, Boca Raton, FL. T. Sakai, T. Matsunaga, Y. Yamamoto, C. Ito, R. Yoshida, S. Suzuki, N. Sasaki, M. Shibayama, and U.-I. Chung. Macromolecules 2008, 41, 5379. J. P. Gong. Soft Matter 2010, 6, 2583. K. Haraguchi. Coll. Polym. Sci. 2011, 289, 455. S. Kondo, H. Sakurai, U.-I. Chung, and T. Sakai. Macromolecules 2013, 46, 7027. N. Murata, A. Konda, K. Urayama, T. Takigawa, M. Kidowaki, and K. Ito. Macromolecules 2009, 42, 8485-8491. L. A. Lyon, and A. Fernandez-Nieves. Annu. Rev. Phys. Chem. 2012, 63, 25. T. Ngai, H. Auweter, and S. H. Behrens. Macromolecules 2006, 39, 8171-8177. B. R. Saunders. Hydrogel Micro- and Nanoparticles, Ed. M. Serpe and L. A. Lyon, Wiley-VCH, New York 2012, 141-161. B. R. Saunders, and B. Vincent. Adv. Coll. Interf. Sci. 1999, 80, 1-25. V. T. Pinkrah, A. E. Beezer, B. Z. Chowdhry, L. H. Gracia, J. C. Mitchell, and M. J. Snowden. Langmuir 2004, 20, 8531-8536. T. Hu, Y. You, C. Pan, and C. Wu. J. Phys. Chem. B 2002, 106, 6659-6662. S. C. Howard, V. S. J. Craig, P. A. FitzGerald, and E. J. Wanless. Langmuir 2010, 26, 14615-14623. T. Hoare, and R. Pelton. Macromolecules 2004, 37, 2544-2550. R. Liu, A. H. Milani, T. J. Freemont, and B. R. Saunders. Soft Matter 2011, 7, 4696-4704. S. Thaiboonrod, A. H. Milani, and B. R. Saunders. J. Mater. Chem. B 2014, 2, 110-119. W. Richtering, and B. R. Saunders. Soft Matter 2014, 10, 3695-3702. T. Cai, G. Wang, S. Thompson, M. Marquez, and Z. Hu. Macromolecules 2008, 41, 9508-9512. Z. Hu, X. Lu, and C. Wang. Adv. Mater. 2000, 12, 1173-1176. J. Hu, T. Kurokawa, T. Nakajima, Z. L. Wu, S. M. Liang, and J. P. Gong. Macromolecules 2014, 47, 3587-3594. S. Lehmann, S. Seiffert, and W. Richtering. J. Am. Chem. Soc. 2012, 134, 15963. J. Hu, T. Kurokawa, K. Hiwatashi, T. Nakajima, Z. L. Wu, S. M. Liang, and J. P. Gong. Macromolecules 2012, 45, 5218-5228. R. Liu, A. H. Milani, J. M. Saunders, T. J. Freemont, and B. R. Saunders. Soft Matter 2011, 7, 92979306. K. Haraguchi, R. Farnworth, A. Ohbayashi, and T. Takehisa. Macromolecules 2003, 36, 5732. J. McParlane, D. Dupin, J. M. Saunders, S. Lally, S. P. Armes, and B. R. Saunders. Soft Matter 2012, 8, 6239-6247. A. H. Milani, A. J. Freemont, J. A. Hoyland, D. J. Adlam, and B. R. Saunders. Biomacromolecules 2012, 13, 2793-2801. M. Gibas, and A. Korytkowska-Walach. Polymer Bulletin 2003, 51, 17-22. S. Zhou, and B. Chu. The Journal of Physical Chemistry B 1998, 102, 1364-1371. L. A. Lyon, J. D. Debord, S. B. Debord, C. D. Jones, J. G. McGrath, and M. J. Serpe. J. Phys. Chem. B 2004, 108, 19099-19108. H. Senff, and W. Richtering. J. Chem. Phys. 1999, 111, 1705-1711. A. S. J. Iyer, and L. A. Lyon. Angew. Chem. Inter. Ed. 2009, 48, 4562-4566. P. J. Flory. Principles of polymer chemistry, Cornell university press, Ithaca 1953. H.-y. Ren, M. Zhu, and K. Haraguchi. Macromolecules 2011, 44, 8516-8526. Z. Shao, A. S. Negi, and C. O. Osuji. Soft Matter 2013, 9, 5492-5500. Z. Zhou, J. V. Hollingsworth, S. Hong, H. Cheng, and C. C. Han. Langmuir 2014, 30, 5739-5746. R. J. Young, and P. A. Lovell. Introduction to polymers, Chapman & Hall, London, 2nd Ed. 1997. E. R. Morris. Carbohydr. Polym. 1992, 17, 65-70. S. Rose, A. Dizeux, T. Narita, D. Hourdet, and A. Marcellan. Macromolecules 2013, 46, 4095-4104.


23

Published on 06 February 2015. Downloaded by University of Prince Edward Island on 07/

GOE pH > pKa 37 oC

GMA


Soft Matter Page 24 of 24

Dynamic mechanical and swelling properties of maleated hyaluronic acid hydrogels.

Tunable swelling and rolling of microgel membranes.

Physics in ordered and disordered colloidal matter composed of poly(N-isopropylacrylamide) microgel particles.

A study of physical and covalent hydrogels containing pH-responsive microgel particles and graphene oxide.

Non-aqueous microgel particles: synthesis, properties and applications.

acrylic acid synthesized by gamma radiation.

Swelling of thermo-responsive hydrogels.

Inner structure of adsorbed ionic microgel particles.

Mechanical properties of alginate hydrogels manufactured using external gelation.

Poly(vinylamine) microgel-dextran composite hydrogels: characterisation; properties and pH-triggered degradation.

Swelling behavior and morphological properties of semi-IPN hydrogels based on ionic and non-ionic components.

Roller compactor: The effect of mechanical properties of primary particles.

Hygroscopic properties of internally mixed particles composed of NaCl and water-soluble organic acids.

Carbonaceous particles reduce marine microgel formation.

The chemical, mechanical, and physical properties of 3D printed materials composed of TiO2-ABS nanocomposites.

Rheological, thermo-mechanical, and baking properties of wheat-millet flour blends.

Hydrogels: swelling, drug loading, and release.

xyloglucan hydrogels.

Investigation of Swelling Behavior and Mechanical Properties of a pH-Sensitive Superporous Hydrogel Composite.

Influence of physical and mechanical properties of amphiphilic biosynthetic hydrogels on long-term cell viability.

Experimental Investigation of Mechanical and Thermal Properties of Silica Nanoparticle-Reinforced Poly(acrylamide) Nanocomposite Hydrogels.

Mechanical Properties and Degradation of Chain and Step Polymerized Photodegradable Hydrogels.

The crosslinking degree controls the mechanical, rheological, and swelling properties of hyaluronic acid microparticles.

Terminal sterilization of alginate hydrogels: efficacy and impact on mechanical properties.