Comparison of Hydrogels Prepared with Ionic-Liquid-Isolated vs

Research Article pubs.acs.org/journal/ascecg

Comparison of Hydrogels Prepared with Ionic-Liquid-Isolated vs Commercial Chitin and Cellulose Xiaoping Shen,†,‡ Julia L. Shamshina,§ Paula Berton,†,∥ Jenny Bandomir,† Hui Wang,† Gabriela Gurau,§,∥ and Robin D. Rogers*,†,∥ †

Department of Chemistry, The University of Alabama, Tuscaloosa, Alabama 35487, United States Key Laboratory of Bio-based Material Science and Technology (Ministry of Education), Northeast Forestry University, 26 Hexing Road, Harbin 150040, China § 525 Solutions, Inc., 720 2nd Street, Tuscaloosa, Alabama 35401, United States ∥ Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada

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‡

S Supporting Information *

ABSTRACT: Physical and/or covalently linked (chemical) hydrogels were prepared from chitin and cellulose extracted with ionic liquid from shrimp shells and wood biomass, respectively, and compared with hydrogels prepared from commercially available biopolymers, practical grade chitin, and microcrystalline cellulose. The highly porous aerogels were formed by initial dissolution of the biopolymers in NaOH/urea aqueous systems using freeze/thaw cycles, followed by thermal treatment (with or without epichlorohydrin as a cross-linker) and supercritical CO2 drying. The ionic-liquid-extracted cellulose pulp and chitin, as well as practical grade chitin could form both stable physical and chemical hydrogels, whereas biopolymers of lower apparent molecular weight such as microcrystalline cellulose required a covalent cross-linker for hydrogel formation and commercially available pure chitin was not suitable for the preparation of hydrogels of either type. Hydrogels prepared from the ionic-liquidextracted biopolymers exhibited properties substantially different from those made from the commercially available biopolymers. Loading of an active ingredient into the hydrogel and its subsequent release was demonstrated using indigo carmine and revealed that the release rate was controlled mainly by the biopolymer concentration of the gel network. KEYWORDS: Hydrogel, Aerogel, Chitin, Cellulose, Ionic liquid, Release

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INTRODUCTION Hydrogels are highly swollen, hydrophilic, three-dimensional (3D) polymeric networks capable of absorbing large amounts of water or biological fluids and swelling.1 Currently, the majority of the hydrogels are manufactured using (meth)acrylic acid or acrylamide, compounds that raise public health concerns.2,3 Considering not only safety, but also biocompatibility, tissue-mimicking consistency, and biodegradability, biopolymer-based hydrogels have been drawing increasing interest and attention.4 Cellulose and chitin, the two most abundant renewable biopolymers on earth, consist of straight chain of β-(1→4)-linked D-glucose, and β-(1→4)-linked Nacetyl-D-glucosamine, respectively. Because of the hydroxyl and/or acetamido groups present in their structures, fused or © 2015 American Chemical Society

amorphous cellulose and chitin chains are highly hydrophilic and potentially suitable to form superabsorbent hydrogels.5,6 In addition to their biodegradability,7,8 swollen hydrogels from cellulose and chitin are elastic but soft and possess diffusive properties identical to those of a liquid, and thus can absorb and release water or biological fluids in a reversible nonirritating manner, making them compatible with living Special Issue: Ionic Liquids at the Interface of Chemistry and Engineering Received: October 30, 2015 Revised: December 13, 2015 Published: December 15, 2015 471

DOI: 10.1021/acssuschemeng.5b01400 ACS Sustainable Chem. Eng. 2016, 4, 471−480

Research Article

ACS Sustainable Chemistry & Engineering

Table 1. Alkali Solvent Selection, Viscosity Values of the Resulting Solutions, and the Maximum Concentration of the Biopolymer in the Optimum Solvent System NaOH/urea x wt %/y wt % (F/Ta cycles)

biopolymer chitin

cellulose

pure-chitin PG-chitin Rec. PGe IL-chitin MCC CRM-POM CRM-175

2/2

4/0

4/4

6/4

7/12

−c − − − − − −

− − − − − − −

− − − − +(6) +(8) +(4) √

Swc Sw Sw Sw +(2) √ +(3) √ +(10)

+(4)c +(8) +(6) +(8) +(2) +(6) Sw

8/4 +(2) +(3) +(3) +(4) +(4) +(6) Sw

√d √ √ √

12/6

b

+(2) +(3) +(3) +(4) − − −

viscosityf (cP)

max. conc.i (wt %)

5.0g 14.1(8)h 8.4(2) 18.8(2) 8.9(1) 9.4(1) 31.0(4)

12.5(3) 4.3(2) 6.5(2) 2.4(2) 5.2(2) 5.4(2) 1.4(2)

b

20/0

+(2) +(3) +(3) +(4) − − −

a F/T: Freeze/thaw. bThese conditions for chitin might result in chitosan formation. c−, insoluble; + , soluble; Sw, insoluble but can swell. dThe optimized solvent for each biopolymer. eRec. PG, Reconstituted PG-chitin from the [C2mim][OAc] solution to remove impurities (100 °C, 1 h; Supporting Information). fViscosity of 1 wt % solution in NaOH/urea at 20 °C (Figure S2). gThe error was lower than 0.1. hThe large error was caused by insoluble impurities in the PG-chitin solution. imax. conc.: maximum concentration in the optimized NaOH/urea system.

tissues.9,10 Consequently, these hydrogels have attracted tremendous attention as excellent candidates for biomedical applications, such as drug delivery,11 wound dressings,12 and tissue engineering matrices.13 Chitin and cellulose hydrogels are usually prepared through a two-step process involving biopolymer dissolution and chain cross-linking. To date, there are only a few specific solvent systems reported to dissolve chitin or cellulose and form hydrogels, such as ionic liquids (ILs),14,15 alkali or alkali/urea (thiourea) aqueous systems,16−18 and polar solvent systems including LiCl/N-methyl-2-pyrolidone (NMP),8,19 LiCl/N,Ndimethylacetamide (DMAc), 20 LiCl/dimethyl sulfoxide (DMSO),21 and saturated CaCl2·2H2O/methanol.22 Among these solvents, alkali/urea aqueous systems are attractive due to their low cost, energy consumption, and toxicity, and the relatively low viscosity of the resulting solutions at room temperature. After dissolution, physical or chemical cross-links are needed to provide structural integrity and thus form hydrogels. Physical cross-links involve various interactions such as chain entanglements, strong van der Waals forces, hydrogen bonds, crystallite associations,23 and/or ionic interactions.24 Chemical cross-links are covalent bonds between polymeric chains themselves or between the polymer(s) and a cross-linker added to gelate the solution.25 Physical hydrogels can be obtained from solution either by curing at a certain temperature,16,18 or by coagulating with an antisolvent in a specific fashion (e.g., molding, casting, or dropping).19,26 Chemical hydrogels can be obtained via cross-linking using irradiation (e.g., electron beam,27 γ-ray,28 or UV29) or using a chemical cross-linker (e.g., epichlorohydrin,9,30,31 1,2,3,4-butanetetracarboxylic dianhydride,8,32 or succinic anhydride7,33). In our previous work, we have developed a series of methods for the isolation of cellulose-rich materials (CRMs)34−36 and chitin (IL-chitin)37,38 by direct dissolution and reconstitution of the biopolymers from their corresponding biomass using ILs. It was found that these IL-isolated biopolymers had particularly higher molecular weights (MWs) than most commercial sources. We were curious whether the unique forms of the biopolymers we extracted from biomass using ILs would provide hydrogels with properties that might differ from the currently available materials. To test this, we utilized these extracted biopolymers for the formation of both physical and chemical hydrogels in NaOH/urea as the solvent system and compared their properties to analogous gels prepared from commercial cellulose and chitin and to hydrogels published in

the literature. The formation, structure and morphology, water absorbency (rehydration), and active ingredient loading and release of these hydrogels are described here.

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RESULTS AND DISCUSSION Biopolymer Extraction and Dissolution in NaOH/Urea. Chitin and cellulosic biopolymers used for this study were respectively extracted from shrimp shells (SS) and poplar, using [C2mim][OAc] and procedures we have previously described (see the Supporting Information for complete experimental details and composition of the biopolymers, Table S1).35,36,38 The materials studied here include IL-chitin (isolated from dried/processed SS using microwave-assisted dissolution38), CRM-175 (extracted from poplar at 175 °C for 30 min followed by regeneration with 50% v/v acetone/H2O35), and CRM-POM (extracted from poplar with polyoxometalate (POM) at 110 °C for 2 h followed by regeneration using 50% v/v acetone/H2 O36). Commercial microcrystalline cellulose (MCC), pure chitin, and practical grade (PG)-chitin, were purchased from commercial suppliers and used for comparison. The literature has reported that commercial cellulose and chitin biopolymers can be dissolved in aqueous NaOH/urea solvent systems utilizing freeze/thaw (F/T) cycles.16,17,39,40 In NaOH/urea systems, the concentration of NaOH is reported to greatly affect biopolymer dissolution due to the ability of NaOH to break hydrogen bonds, whereas urea (generally above 4 wt %) is suggested to act as a hydrogen bond donor, creating a cellulose inclusion complex and preventing reaggregation of the biopolymer chains. Here, we verified that F/T treatment is also a suitable approach for the dissolution of IL-extracted biopolymers in NaOH/urea. To accelerate dissolution, we adopted an ethanol/dry ice bath for freezing instead of a refrigerator as noted in the literature. We first attempted to replicate this dissolution procedure for the IL-extracted biopolymers using 8 wt % NaOH/4 wt % urea and 7 wt % NaOH/12 wt % urea aqueous solutions; systems reported to dissolve chitin and cellulose, respectively.41,42 We found (Table 1) that different NaOH concentrations and numbers of F/T cycles were required to dissolve the biopolymers. For chitin, a minimum of 7 wt % NaOH in NaOH/urea was required for its dissolution, whereas for cellulose, only the 4−8 wt % NaOH concentrations were able to dissolve MCC and CRM-POM, and 4−6 wt % to dissolve CRM-175. The optimized conditions were chosen as those in which the biopolymer was dissolved using the least number of 472


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(b) adding a chemical cross-linker, epichlorohydrin (ECH), to form chemical hydrogels. The flowchart for each process is shown in Figure 1.

F/T cycles: 8 wt % NaOH/4 wt % urea for chitin, 6 wt % NaOH/4 wt % urea for MCC and CRM-POM; and 4 wt % NaOH/4 wt % urea for CRM-175. It is noteworthy that using any given NaOH/urea system, the number of F/T cycles required depended on the biopolymer, e.g., IL-chitin needed more F/T cycles than pure chitin in the same NaOH/urea solution. In addition, the viscosities of the 1 wt % chitin solutions in NaOH/urea at 20 °C increased from 5 cP for pure chitin to 18.8 cP for IL-chitin, whereas for cellulose solutions the viscosities of the 1 wt % solutions increased from 8.9 cP for MCC to 31 cP for CRM-175. Both of these observations suggest that the biopolymers obtained by IL extraction from raw biomass have higher MWs than the commercial biopolymers. A reconstitution process of PG-chitin with IL (Rec. PG) was performed to remove insoluble impurities. It was found that although the purity of Rec. PG was improved and the errors in viscosity were decreased, the viscosity of the Rec. PG solution, 8.4 cP, was substantially lower than that of PG-chitin (14.1 cP), suggesting that depolymerization might occur during IL dissolution. To determine the biopolymer concentrations that can be dissolved in a corresponding NaOH/urea system, the concentration above which the solution solidified within 2 min after cooling to room temperature was determined, i.e., the maximum concentration. Solutions of each biopolymer in the optimum NaOH/urea at 1 wt % were prepared using F/T treatment and then the biopolymer concentration in the solution was increased stepwise in 0.1 wt % increments, followed by several F/T cycles. The additions were continued until immediate gelation occurred at room temperature. It should be noted here that increasing the biopolymer concentration above the maximum concentration led to gelation of the solution, however, the resulting hydrogel was too weak to transfer from the mold (vial) and we considered these to be weak “pseudo-hydrogels.” Among all the biopolymers tested, CRM-175 and IL-chitin demonstrated the lowest maximum concentrations of 1.4 and 2.4 wt %, respectively (Table 1), again a likely indicator of a higher MW. The maximum concentrations for MCC (5.2 wt %), CRM-POM (5.4 wt %), PG chitin (4.3 wt %), and Rec. PG (6.5 wt %) were all similar and low. The maximum concentration found for pure chitin was much higher (12.5 wt %), again suggesting the much lower MW of this polymer, which results from its multistep processing. Interestingly, the maximum concentrations observed were independent of the particle size (not shown in the tables). However, smaller particles did result in faster dissolution, i.e., fewer F/T cycles. For example, 1 F/T cycle was needed for ILchitin dissolution when the particle size was 250 μm. This can most likely be attributed to the higher surface area and easier access of the smaller particles, although we cannot rule out the possibility of a reduction of MW due to mechanical degradation during grinding. Formation of Hydrogels. Although coagulation in acid, salt, or organic antisolvent is frequently employed for hydrogel formation from biopolymer/NaOH/urea solutions,43 when attempting to form bulk hydrogels or hydrogels from solutions of low concentrations,44 thermally induced gelation is considered to be more practicable. Therefore, to produce stable bulk hydrogels, two strategies were attempted here: (a) curing, i.e., keeping the solution at a certain temperature for a given amount of time to afford firm physical cross-linking, and

Figure 1. Processes for making physical and chemical hydrogels with IL-chitin (left) and CRM-175 (right) as examples. Chitin gel code XXm-n: XX represents the chitin type, m is the chitin concentration, and n is the mass ratio of ECH to chitin.

Physical Hydrogels. The effect of curing temperature on the time required to form firm physical hydrogels from solutions at maximum concentrations was studied (Table S2). At 30 °C, longer times (usually >12 h) were required to form firm hydrogels from either cellulose or chitin. Curing time significantly decreased at higher temperatures, i.e., 4 h at 60 °C for chitin or 50 °C for cellulose. We therefore selected heating regimes of 50 °C for cellulose and 60 °C for chitin, attempting to produce strong physical hydrogels in a shorter time (4 h). The effect of biopolymer concentration on hydrogel formation was also studied to determine the minimum biopolymer concentrations required to prepare physical hydrogels (Table 2). Only those biopolymers with higher apparent MWs, i.e., IL-chitin, PG-chitin, and CRM-175, were 473


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Table 2. Effect of Biopolymer Concentration on the Formation of Physical Hydrogels at 50 °C (for Cellulose) or 60 °C (for Chitin) for 4 h biopolymer chitin

cellulose

pure chitin PG-chitin Rec. PGa IL-chitin MCC CRM-POM CRM-175

NaOH/urea (x wt %/y wt %)

1.0 wt %

1.5 wt %

2.0 wt %

3.0 wt %

4.0f wt %

8/4 8/4 8/4 8/4 6/4 6/4 4/4

      √ Ph-CRM-175

 pseudoc  pseudo   N/A

 √ PG-2-0d pseudo √ IL-2-0d   N/A

 √ pseudo N/Ae pseudo pseudo N/A

 √ pseudo N/A pseudo pseudo N/A

b

a

Rec. PG: Reconstituted PG-chitin from [C2mim][OAc] to remove impurities. bNo hydrogel was formed. cpseudo: The resulting gel was not strong enough to maintain integrity during transfer. dChitin gel code XX-m-n: XX represents the chitin type, m is the chitin concentration, and n is the mass ratio of ECH to chitin. eN/A: limited by the maximum concentration of the biopolymer. fThe results were the same even at maximum biopolymer concentrations.

Scheme 1. Chemical Cross-Linking Reaction between ECH and Biopolymera

a

Chitin is shown. Reproduced from Ref 47 with permission from the Royal Society of Chemistry.

Table 3. Preparation of Chemical Hydrogels at 50 °C/1 h for Cellulose and 60 °C/2 h for Chitin biopolymer chitin

pure chitin PG-chitin Rec. PGb IL-chitin

cellulose

MCC CRM-POM CRM-175

conc. (wt %)

mass ratio of ECH/biopolymerf

gel codeg

ECH consumptionh (g)

1 2a 1 2 2c 1 2 4d 4 1e

10 10 10 5 5 10 5 2.5 2.5 10

  √ PG-1-10 √ PG-2-5 too weak √ IL-1-10 √ IL-2-5 √ MCC √ CRM-POM √ CRM-175

N/A N/A N/A 0.0033(2) N/A N/A 0.0033(2) N/A N/A 0.0015(2)

a Even increasing to maximum concentration, no firm gels from pure chitin were formed. bRec. PG: Reconstituted PG-chitin from [C2mim][OAc] to remove impurities. cThis concentration was used attempting to produce gels for comparison with PG-2-5. dLower concentration led to very weak hydrogels. eThe concentration is limited by the maximum concentration in NaOH/urea. fMass ratio of ECH/biopolymer: e.g., 10 represents the mass of ECH added is 10 times that of the biopolymer in the solution. gChitin gel code XX-m-n: XX represents the chitin type, m is the chitin concentration, and n is the mass ratio of ECH to chitin. hThe real mass of ECH consumed for cross-linking 1 g of the solution.

formation (molecular association), an opaque gel is obtained.20 Further, the high gelation temperature (50 or 60 °C) increased the degree of phase separation and thereby heterogeneities (i.e., the number and size of polymer aggregates),45,46 resulting in the complete opacity of chitin hydrogels. After washing with DI water, the chitin hydrogels appeared ivory-colored possibly due to the removal of NaOH and urea molecules. Ph-CRM-175 had a yellow color before and after washing, probably caused by the presence of lignin. The physical chitin hydrogels appeared swollen after washing, whereas Ph-CRM-175 hardly swelled, suggesting overentanglement with much stronger chain intertwining and hydrogen-boding developing during physical cross-linking of the cellulosic biopolymer chains. Chemical Hydrogels. The generalized mechanism of crosslinking of the biopolymers with ECH is shown in Scheme 1.47 Lower heating time was needed to form chemical hydrogels

able to produce stable physical hydrogels from solutions of concentrations at and above 2 wt % (for chitin) or 1 wt % (for CRM-175). The remaining biopolymers studied, i.e., pure chitin, Rec. PG, MCC, and CRM-POM, could not form physical gels at lower concentrations or only formed pseudo gels at higher concentrations, regardless of the higher purity. For the comparative data below, we have designated the physical hydrogels of 2 wt % from PG- and IL-chitin as PG-2-0 and IL-2-0, respectively, and the cellulosic physical gel as PhCRM-175. Freshly prepared chitin physical hydrogels appeared yellowish and nontransparent. The opacity is primarily caused by the architecture of the macromolecules or the hydrogel formation mechanism (phase separation vs crystallite formation), which was previously reported as the key factor for the transparency of the hydrogel; when phase separation precedes crystallite 474


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Figure 2. Photographs of (a) IL-chitin and (b) cellulose gels (original gels, left; alcogels, middle; aerogels, right) during preparation. Chitin gel code XX-m-n: XX represents the chitin type, m is the chitin concentration, and n is the mass ratio of ECH to chitin.

the ethanol container (for the following solvent exchange and supercritical drying). Structural confirmation of chemical cross-linking was assessed through Fourier transform infrared (FTIR) spectroscopy (taking chitin as a benchmark, Figure S3, Supporting Information). A series of narrow absorption bands, typical for chitin, including O−H stretch (3445 cm−1), different types of CH stretches (3099, 2918, 2870 cm−1), amide I (CO stretch at 1653 and 1620 cm−1 due to the occurrence of hydrogen bonding CO···HN and CO···HOCH2, respectively48), amide II (NH bend and CN stretch at 1550 cm−1), amide III (complex vibrations of NHCO at 1305 cm−1),49 and COC and CO stretches (four intensive bands at 1153, 1110, 1065, and 1022 cm−1) were detected. Although physical gels exhibit the typical FTIR signature of chitin, the FTIR spectra of chemically cross-linked gels look slightly different. If we compare, for example, the band corresponding to the stretch of the C−O bond in chemical (1028 cm−1) and physical (1022 cm−1) gels, the latter looks broader and more pronounced, an indication that there are more OH groups bonded to the carbon backbone. There is also a noticeable difference in the amide I and II bands. In native chitin, the amide I band at 1620 cm−1 is higher in intensity than the one at 1653 cm−1, and the amide II band is higher than the amide I bands. In chemically cross-linked chitin, the relative intensities of the two amide I bands are reversed and amide II becomes lower than amide I, suggesting that (a) chemical cross-linking results in shortening the distances between biopolymeric molecules thus CO and NH become involved in the hydrogen bond interactions to a larger extent; (b) chemical cross-linking may occur at the CH2OH sites. Because of the low cross-linking degree, other changes were not detected in the FTIR spectra. Preparation of Aerogels. Physical and chemical hydrogels were oven-dried, freeze-dried, or supercritically CO2 dried (ScCO2-dried). Oven-drying totally destroyed the structure of the hydrogel network, leading to collapse of the pores due to the recrystallization of the biopolymers (Figure S4). Additionally, powder X-ray diffraction (PXRD) analysis showed that the (020) crystalline plane of α-chitin at 9.2° or the (11̅0) plane of

(1 h for cellulose, and 2 h for chitin) than that needed for physical hydrogels (4 h) at the same temperature, indicating the effectiveness of ECH in cross-linking. The real mass of ECH consumed for cross-linking was estimated taking into account the MW increase due to the incorporation of −CH2CH(OH)CH2− connecting units, and under the assumption that the mass of biopolymers in the chemical gel from the biopolymer solution (1 g) was equal to that in the physical gel of the same biopolymer concentration (see the Supporting Information for calculation). The consumption of ECH for gel formation was found to be low, i.e., 0.0033 g for 2 wt % chitin gels and 0.0015 g for 1 wt % CRM-175 gels (Table 3), with others unable to be calculated due to the failure of physical gel formation. The influence of biopolymer concentration on chemical gel formation was tested, and it was found that chemical hydrogels were formed from the three biopolymer solutions at concentrations that successfully formed physical hydrogels (2 wt % PG- and IL-chitin, and 1 wt % CRM-175). Additionally, 1 wt % chitin (PG- and IL-chitin) solutions and 4 wt % CRMPOM and MCC solutions that could not form firm physical gels did produce chemical hydrogels, whereas pure chitin of the lowest MW was not able to form either type of hydrogel. After washing with DI water, swelling was observed in both chitin and cellulose hydrogels. The chitin chemical hydrogels appeared similar (nontransparent) to the physical ones except for the much higher swollen volumes after washing (Table S3, Supporting Information). Although the preparation conditions were similar, cellulosic hydrogels exhibited higher transparency than chitin ones, indicating a lower degree of phase separation. In particular, MCC hydrogels had the highest transmittance among all hydrogels before and after washing, whereas CRM hydrogels of lower purity became translucent after dramatic swelling during washing. The transparency of the CRM hydrogels increased after swelling compared with the asprepared gels, which may suggest that transparency of cellulosic hydrogels is also related to the degree of swelling. As expected, the firmness of the 1 wt % swollen chitin gels were lower compared with analogous 2 wt % gels, whereas the highly absorbent cellulosic gels were so soft and sticky that extra care had to be taken when transferring these from washing bath to 475


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Figure 3. SEM images of surfaces and cross sections of IL-chitin (IL-2-5, top) and cellulose (CRM-175, bottom) aerogels at magnifications in the range of 500−2500 and 2000−4000, respectively.

Table 4. Shrinkage, Density, and Porosity of Chitinous and Cellulosic Gels gel codea chitin

cellulose

PG-2-0 IL-2-0 PG-1-10 PG-2-5 IL-1-10 IL-2-5 MCC CRM-POM CRM-175 Ph-CRM-175

Salcob (%)

Saerob (%)

density (×10−2 g/cm3)

porosity (%)

−0.3 −0.5c −34(3) −9.0(3) −37(3) −24(3) −76(2) −71(3) −58(2) 0

−1.7 −20(3) −57(2) −38(2) −65(1) −48(2) −88(3) −84(3) −87(2) 0

2.6(1) 2.6(2) 2.4(1) 3.3(1) 2.7(1) 3.4(1) 18(3) 7.7(5) 5.8(4) 5.9(1)

96(1) 95(1) 95(1) 94(1) 94(1) 94(1) 62(3) 87(2) 91(2) 90(2)

c

c

a

Chitin gel code XX-m-n: XX represents the chitin type, m is the chitin concentration, and n is the mass ratio of ECH to chitin. bSalco and Saero: Volume shrinkage of alcogels and aerogels compared with the original gels, respectively. cThe deviation is higher than the average value.

cellulosic aerogels were much more compact, higher magnification was required. Each aerogel had a characteristic channellike structure of phase separation (so-called spinodal decomposition52) resulting from the thermodynamic instability of the biopolymer/NaOH/urea solutions. The chitin aerogels consisted of a discontinuous hierarchical porous network, which entailed a well-developed macroporous system with pore diameters up to 40 μm and a nanoscale substructure. Contrarily, the cellulosic aerogels were much more compact and homogeneous, consistent with the lower phase separation and higher transparency. Most of the pores in the cellulosic aerogels were unobservable and the maximum pore size was less than 1 μm. The CRM aerogels also included a few uneven fibrils, possibly due to the presence of lignin or hemicellulose impurities. Shrinkage and Porosity. Air-drying led to collapse of the gels with up to 98% shrinkage compared with the original hydrogels, whereas ScCO2-drying maintained the pore structure and provided much lower shrinkage. During both solvent exchange and ScCO2-drying, the volumes of the physical gels hardly changed, whereas all chemical hydrogels suffered relatively severe volume reduction (Table 4). Such differences in shrinkage could be explained by the proposed mechanism shown in Figure 4. Specifically, in chemical hydrogels, the polymer chains are likely to be less intertwined than those in physical gels due to the presence of the crosslinker and the shorter time required for preparation. When immersed in ethanol and then ScCO2-dried, the stretched biopolymer chains in chemical hydrogels can be re-entangled, resulting in significant shrinking. Less entanglement might also

cellulose II at 11.8° shifted (partially) to 7.6° after chemical cross-linking (Figure S5). (Although these observations suggest a change in crystalline form induced by the chemical crosslinking, additional characterization techniques are needed to understand completely these changes.) Although freeze-dried gels did not collapse, drying gels using this process required several days. ScCO2-drying was employed to provide porous aerogels. The hydrogels were first immersed in ethanol forming alcogels, which were much more compact and firmer than the original hydrogels. Chitin and CRM-175 alcogels appeared glassy and very regular, whereas MCC and CRM-POM alcogels were rough and lumpy (Figure 2). After ScCO2-drying, all of the resulting aerogels were lightweight, and the PXRD analysis showed that the crystalline peak at 19.2° (for 110 plane of αchitin) or 20.0° (for 110 plane of cellulose II) almost disappeared and an amorphous peak at about 11.8° was observed (Figure S5). The amorphous scattering for the aerogels is different from that of amorphous cellulose or chitin (ca. 16° 50,51) which may be an important clue for understanding the molecular mechanisms of aerogel structure. Most of the aerogels appeared white or nearly white except for the CRM-POM aerogel that exhibited a yellow color. Additionally, cellulosic aerogels were much harder and stronger (by pinch testing) than the chitin aerogels, which might be associated with both the nature of the biopolymer and the more compact aerogel microstructure. Morphology of Aerogels. The surfaces and cross sections of both the chitin and cellulosic aerogels were studied using scanning electron microscopy (SEM, Figure 3). As the 476


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The presence of lignin did not inhibit the water uptake of CRM hydrogels. Out of all gels, the CRM-175 chemical hydrogel showed the highest water uptake (9300% or 93 times the weight of the aerogel), followed by the higher MW chitin gels IL-1-10 (6800%), IL-2-5 (4900%), and finally IL-2-0 (4350%; Figure 5). These results suggest that higher

Figure 4. Proposed structural change of chemical and physical gels before and after shrinking caused by solvent exchange and ScCO2drying.

Figure 5. Rehydration ratio of chitin and cellulosic hydrogels after soaking the aerogels in water at room temperature for 24 h. Chitin gel code XX-m-n, where XX represents the chitin type, m is the chitin concentration, and n is the mass ratio of ECH to chitin.

be the reason for the higher shrinkage of the chemical chitin hydrogels at 1 wt % concentration than those at 2 wt %. In other words, the bigger pores in the more swollen original hydrogels, even with thinner walls in the 1 wt % gels, are assumed to be easier to collapse during solvent exchange and ScCO2-drying. The type of biopolymer also had an effect on shrinkage. Chemical hydrogels of cellulose sharply shrank after drying, forming both denser and harder aerogels than chitin hydrogels. The MW of biopolymers seemed to have little impact on the total shrinking of the gels, which can be deduced from the CRM-175 and CRM-POM chemical gels (Table 4). Additionally, the purity of the biopolymers might play a role. PG-2-5 (made from PG-chitin as received) showed less shrinkage than purer IL-2-5 (made from IL-chitin isolated from SS with [C2mim][OAc]), although we cannot completely eliminate the influence of the lower MW of PG-chitin. All of the chitin aerogels in this work had densities an order of magnitude lower (2.4−3.4 × 10−2 g/cm3) than those reported in the literature (12−27 × 10−2 g/cm3),45,53 which may be related to the different solvent systems, chitin concentrations, or gelation methods (heating or coagulation) used. Moreover, the densities we obtained approached those of chitin nano-whisker-based aerogels (0.5−2.1 × 10 −2 g/cm3).54−56 These low densities correlate well with the observed high porosities (94−96%). The cellulosic aerogels were denser than the chitin gels, in agreement with their appearances in the SEM images. Their density and porosity were roughly in agreement with the literature data.57,58 Of all the cellulosic aerogels, CRM-175 gels (physical and chemical) had the lowest densities and thus the highest porosities, whereas the MCC chemical gel possessed the highest density and thus the lowest porosity. Rehydration Properties. The water rehydration ability of the hydrogels was tested by placing the aerogels in water for 24 h to evaluate both the rehydration ratio and rate. Immediately after placing the hydrogels into DI water, all aerogels would first shrink before swelling due to the gas venting from the aerogels. Rehydrated cellulosic hydrogels were quite tough, whereas the chitin gels were relatively fragile, which may affect their service life and recycling use.

biopolymer MW, lower biopolymer concentration, and chemical gel type are favorable parameters in achieving higher ultimate aerogel water uptake capacity. These three conditions favor the extension of the polymer chains and thus the formation of bigger pores in the rehydrated hydrogels, which might explain the higher rehydration ratios. The rehydration rate was evaluated by continuously monitoring hydrogel mass increase during water uptake (Figure 6a). The rehydration rate depended on the biopolymer

Figure 6. (a) Mass recoveries of hydrogels as a function of time during rehydration; (b) cumulative dye release from loaded hydrogels in phosphate buffer saline (PBS) over time (the insets are the loaded hydrogels). Chitin gel code XX-m-n, where XX represents the chitin type, m is the chitin concentration, and n is the mass ratio of ECH to chitin.

concentration, i.e., 1 wt % chitin hydrogels rehydrated faster than the 2 wt % gels, presumably due to faster water diffusion in the bigger pores of the former. The pore structure of the aerogels also affected the rate of water uptake, with cellulose gels of denser structure absorbing water much slower than chitin gels because their microporous network is harder to unfold. MCC and CRM-POM chemical hydrogels absorbed water particularly slowly because both were the most compact aerogel structures and contained the highest biopolymer concentrations. 477


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biomass, we were able to prepare “physical” (no cross-linker) and/or “chemical” (using a cross-linker) hydrogels. The ILextracted biopolymers of apparent higher MWs (CRM-175, ILchitin) and PG-chitin could form both stable physical and chemical hydrogels, whereas lower MW polymers (Rec. PG, CRM-POM, and MCC) required a covalent cross-linker for hydrogel formation. Low MW pure chitin was not suitable for the preparation of hydrogels of either type. The hydrogels were supercritically dried producing amorphous, lightweight, and porous aerogels. Both chitin and cellulose aerogels showed high water absorbency, especially those prepared from CRM-175 and IL-1-10 and chemically cross-linked, again most likely due to the apparent higher MWs and lower chain entanglement (due to the incorporation of the cross-linker and the low biopolymer concentration). The results obtained from dye loading and release suggest the potential use of both chitin and cellulose hydrogels to effectively load and release active species. The gels with higher biopolymer concentration resulting in smaller pores exhibited increased dye loading capacity. As with water uptake, the release rate was mostly affected by the biopolymer concentration of the hydrogel, whereas the amount of dye and type of biopolymer had less effect. We postulate that the use of chitin and cellulose hydrogels for drug delivery applications has great promise, but further research is needed. For example, the mechanical properties of chitin and cellulose hydrogels and aerogels, lowering the burst release (through surface extracting or coating), and the biocompatibility of CRM gels (the effect of lignin content) should be investigated. Considering the unique high strength of cellulosic aerogels, we think that these materials may also find use in other fields, such as thermal insulation and tissue engineering. For chitin hydrogels, the degree of deacetylation may be worth studying to introduce antimicrobial properties.

Although the aerogels could be well rehydrated, the volumes and masses of the fully rehydrated hydrogels were lower than observed for the original gels. Mass recoveries (calculated using eq 7, Supporting Information) for the chitin hydrogels depended on chitin concentration, with higher concentrations resulting in higher recoveries (Figure 6a), which was likely to be related to the lower shrinkage (collapse) of these hydrogels during drying (Table 4, Saero column). For this same reason, the chemical cellulose hydrogels with higher shrinkage showed much lower recoveries than almost all chitin hydrogels. PGchitin hydrogels recovered less than the IL-chitin ones likely due to the presence of impurities and the lower MW. Dye Loading and Release. To test the concept of pharmaceutical loading and release, all cellulose and chitin aerogels were loaded with indigo carmine, by placing the aerogels in 1 mg/mL dye aqueous solutions. Dye molecules successfully diffused into the swollen hydrogels as demonstrated by the dark blue color of the loaded gels (Figure 6b). Dye loading in the hydrogel was calculated by determining the dye concentration of the aqueous solution before and after loading. Although we expected total dye loading in the hydrogels to be related to the rehydration ratio, this was not the case: IL-2-5 showed higher dye loading (45 mg/g) than CRM-175 (29 mg/g) and IL-1-10 (28 mg/g), opposite to the rehydration order CRM-175 > IL-1-10 > IL-2-5. This may result in the conclusion that during dye loading, smaller pores (higher concentration and lower water absorbency) of the hydrogels might lead to a stronger interaction of the biopolymer with the dye, thus increasing the loading capacity of the hydrogels. The dye release was studied by immersing the loaded gels into phosphate buffer saline (PBS) solution. In all cases, a typical diffusion-controlled release profile59 was observed from the cumulative release plot (Figure 6b), which includes a rapid burst release of the dye near the surface, followed by a slower release of the dye located within the hydrogel network. The burst release led to dye losses of over 80% in 1 wt % hydrogels, but as low as 30−40% in hydrogels of higher concentrations, indicating that the release rate was primarily controlled by the biopolymer concentration, where lower concentrations led to higher rehydration and thus bigger pores exhibiting faster release. The 1 wt % hydrogels exhibited steep dye release within 3 h, whereas 2 or 4 wt % hydrogels released the dye much more slowly within 24 h. These release times roughly matched with the reported duration time of drugs permeated in hydrogel systems.60 The dye loading also influenced the release rate, PG2-0 (with a smaller dye loading of 25 mg/g) released slightly faster than other 2 wt % chitin gels. In addition, though at the same concentration and with similar dye loading, CRM-POM gel had higher release rate than MCC gel, likely due to the different interactions between various biopolymers (cellulose, hemicellulose, and lignin) and the dye molecules. Additionally, the aerogels were immersed in dye/ethanol solution followed by one more ScCO2-drying step to determine the dye molecule structure in the gels. A crystalline form of the dye molecules was not detected in the gel (PXRD spectra shown in Figure S6), and thus precipitation of the dye into the pores of the gels was ruled-out.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acssuschemeng.5b01400. Isolation of biopolymers with [C2mim][OAc], determination of purity of the biopolymers, measurement of the viscosity of biopolymer/NaOH/urea solutions, supercritical CO2 drying, calculation of ECH consumption, characterization methods (PXRD and SEM), and volumes and masses of all gels (PDF).

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AUTHOR INFORMATION

Corresponding Author

*R.D.R. E-mail: [email protected] Present Address

H. Wang. Institute of Process Engineering, Chinese Academy of Sciences, No. 1 Beierjie Zhongguancun Haidian District, Beijing 100190, China. Notes

The authors declare the following competing financial interest(s): Dr. Robin D. Rogers has partial ownership of 525 Solutions. Dr. Shamshina is full-time employee of 525 Solutions. Dr. Gabriela Gurau is part-time employee of 525 Solutions. The University of Alabama and McGill University maintain approved Conflict of Interest Management Plans.

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CONCLUSIONS By taking advantage of the ability of ionic liquids to extract chitin or CRM of higher MWs directly from the corresponding 478


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(16) Chen, C.; Li, D.; Yano, H.; Abe, K. Dissolution and gelation of α-chitin nanofibers using a simple NaOH treatment at low temperatures. Cellulose 2014, 21, 3339−3346. (17) Zhou, J. P.; Zhang, L.; Cai, J.; Shu, H. Cellulose microporous membranes prepared from NaOH/urea aqueous solution. J. Membr. Sci. 2002, 210, 77−90. (18) Weng, L.; Zhang, L.; Ruan, D.; Shi, L.; Xu, J. Thermal gelation of cellulose in a NaOH/thiourea aqueous solution. Langmuir 2004, 20, 2086−2093. (19) Yilmaz, E.; Bengisu, M. Preparation and characterization of physical gels and beads from chitin solutions. Carbohydr. Polym. 2003, 54, 479−488. (20) Ishii, D.; Tatsumi, D.; Matsumoto, T.; Murata, K.; Hayashi, H.; Yoshitani, H. Investigation of the structure of cellulose in LiCl/DMAc solution and its gelation behavior by small-angle X-ray scattering measurements. Macromol. Biosci. 2006, 6, 293−300. (21) Wang, Z. G.; Liu, S. L.; Matsumoto, Y.; Kuga, S. Cellulose gel and aerogel from LiCl/DMSO solution. Cellulose 2012, 19, 393−399. (22) Tamura, H.; Nagahama, H.; Tokura, S. Preparation of chitin hydrogel under mild conditions. Cellulose 2006, 13, 357−364. (23) Van Vlierberghe, S.; Dubruel, P.; Schacht, E. Biopolymer-based hydrogels as scaffolds for tissue engineering applications: A review. Biomacromolecules 2011, 12, 1387−1408. (24) Shu, X. Z.; Zhu, K. J. Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure. Int. J. Pharm. 2002, 233, 217−225. (25) Hennink, W. E.; van Nostrum, C. F. Novel crosslinking methods to design hydrogels. Adv. Drug Delivery Rev. 2012, 64, 223−236. (26) Mao, Y.; Zhou, J.; Cai, J.; Zhang, L. Effects of coagulants on porous structure of membranes prepared from cellulose in NaOH/ urea aqueous solution. J. Membr. Sci. 2006, 279, 246−255. (27) Zhao, L.; Mitomo, H.; Yosh, F. Synthesis of pH-sensitive and biodegradable CM-cellulose/chitosan polyampholytic hydrogels with electron beam irradiation. J. Bioact. Compat. Polym. 2008, 23, 319− 333. (28) Hara, K.; Iida, A.; Yano, K.; Nishida, T. Metal ion absorption of carboxymethylcellulose gel formed by γ-ray irradiation for the environmental purification. Colloids Surf., B 2004, 38, 227−230. (29) Petrov, P.; Petrova, E.; Stamenova, R.; Tsvetanov, C. B.; Riess, G. Cryogels of cellulose derivatives prepared via UV irradiation of moderately frozen systems. Polymer 2006, 47, 6481−6484. (30) Zhou, J.; Chang, C.; Zhang, R.; Zhang, L. Hydrogels prepared from unsubstituted cellulose in NaOH/Urea aqueous solution. Macromol. Biosci. 2007, 7, 804−809. (31) Chang, C. Y.; Peng, J.; Zhang, L. N.; Pang, D. W. Strongly fluorescent hydrogels with quantum dots embedded in cellulose matrices. J. Mater. Chem. 2009, 19, 7771−7776. (32) Kono, H.; Zakimi, M. Preparation, water absorbency, and enzyme degradability of novel chitin- and cellulose/chitin-based superabsorbent hydrogels. J. Appl. Polym. Sci. 2013, 128, 572−581. (33) Gurgel, L. V. A.; Junior, O. K.; Gil, R. P. D. F.; Gil, L. F. Adsorption of Cu(II), Cd(II), and Pb(II) from aqueous single metal solutions by cellulose and mercerized cellulose chemically modified with succinic anhydride. Bioresour. Technol. 2008, 99, 3077−3083. (34) Sun, N.; Rahman, M.; Qin, Y.; Maxim, M. L.; Rodríguez, H.; Rogers, R. D. Complete dissolution and partial delignification of wood in the ionic liquid 1-ethyl-3-methylimidazolium acetate. Green Chem. 2009, 11, 646−655. (35) Li, W.; Sun, N.; Stoner, B.; Jiang, X.; Lu, X.; Rogers, R. D. Rapid dissolution of lignocellulosic biomass in ionic liquids using temperatures above the glass transition of lignin. Green Chem. 2011, 13, 2038−2047. (36) Cheng, F.; Wang, H.; Rogers, R. D. Oxygen enhances polyoxometalate-based catalytic dissolution and delignification of woody biomass in ionic liquids. ACS Sustainable Chem. Eng. 2014, 2, 2859−2865. (37) Barber, P. S.; Griggs, C. S.; Bonner, J. R.; Rogers, R. D. Electrospinning of chitin nanofibers directly from an ionic liquid extract of shrimp shells. Green Chem. 2013, 15, 601−607.

ACKNOWLEDGMENTS The authors thank 525 Solutions, Inc., the DOE SBIR Office of Science (DE-SC0010152) and the China Scholarship Council (No. 201306600007) for financial support.

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ABBREVIATIONS [C2mim][OAc], 1-ethyl-3-methylimidazolium acetate CRM-175, cellulose-rich material isolated using IL at 175 °C CRM-POM, cellulose-rich material isolated using IL with polyoxometalate (POM) ECH, epichlorohydrin F/T, freeze/thaw IL, ionic liquid IL-chitin, chitin isolated from shrimp shells (SS) with IL MCC, microcrystalline cellulose MW, molecular weight PG-chitin, practical-grade chitin Rec. PG, reconstituted PG-chitin with IL ScCO2-drying, supercritical CO2 drying

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REFERENCES

(1) Klouda, L.; Mikos, A. G. Thermoresponsive hydrogels in biomedical applications. Eur. J. Pharm. Biopharm. 2008, 68, 34−45. (2) Peppas, N. A.; Bures, P.; Leobandung, W.; Ichikawa, H. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm. 2000, 50, 27−46. (3) Yoshii, E. Cytotoxic effects of acrylates and methacrylates: Relationships of monomer structures and cytotoxicity. J. Biomed. Mater. Res. 1997, 37, 517−524. (4) Hunt, N. C.; Grover, L. M. Cell encapsulation using biopolymer gels for regenerative medicine. Biotechnol. Lett. 2010, 32, 733−742. (5) Chang, C. Y.; Zhang, L. N. Cellulose-based hydrogels: Present status and application prospects. Carbohydr. Polym. 2011, 84, 40−53. (6) Kumar, M. N. V. R. A review of chitin and chitosan applications. React. Funct. Polym. 2000, 46, 1−27. (7) Yoshimura, T.; Uchikoshi, I.; Yoshiura, Y.; Fujioka, R. Synthesis and characterization of novel biodegradable superabsorbent hydrogels based on chitin and succinic anhydride. Carbohydr. Polym. 2005, 61, 322−326. (8) Kono, H.; Fujita, S. Biodegradable superabsorbent hydrogels derived from cellulose by esterification cross-linking with 1,2,3,4butanetetracarboxylic dianhydride. Carbohydr. Polym. 2012, 87, 2582− 2588. (9) Chang, C. Y.; Chen, S.; Zhang, L. N. Novel hydrogels prepared via direct dissolution of chitin at low temperature: structure and biocompatibility. J. Mater. Chem. 2011, 21, 3865−3871. (10) Muller, F. A.; Muller, L.; Hofmann, I.; Greil, P.; Wenzel, M. M.; Staudenmaier, R. Cellulose-based scaffold materials for cartilage tissue engineering. Biomaterials 2006, 27, 3955−3963. (11) Ding, F.; Shi, X.; Jiang, Z.; Liu, L.; Cai, J.; Li, Z.; Chen, S.; Du, Y. Electrochemically stimulated drug release from dual stimuli responsive chitin hydrogel. J. Mater. Chem. B 2013, 1, 1729−1737. (12) Murakami, K.; Aoki, H.; Nakamura, S.; Nakamura, S.; Takikawa, M.; Hanzawa, M.; Kishimoto, S.; Hattori, H.; Tanaka, Y.; Kiyosawa, T.; Sato, Y.; Ishihara, M. Hydrogel blends of chitin/chitosan, fucoidan and alginate as healing-impaired wound dressings. Biomaterials 2010, 31, 83−90. (13) Zaborowska, M.; Bodin, A.; Bäckdahl, H.; Popp, J.; Goldstein, A.; Gatenholm, P. Microporous bacterial cellulose as a potential scaffold for bone regeneration. Acta Biomater. 2010, 6, 2540−2547. (14) Wu, Y.; Sasaki, T.; Irie, S.; Sakurai, K. A novel biomass-ionic liquid platform for the utilization of native chitin. Polymer 2008, 49, 2321−2327. (15) Deng, M.; Zhou, Q.; Du, A.; van Kasteren, J.; Wang, Y. Preparation of nanoporous cellulose foams from cellulose-ionic liquid solutions. Mater. Lett. 2009, 63, 1851−1854. 479


Research Article

ACS Sustainable Chemistry & Engineering (38) Shamshina, J. L.; Gurau, G.; Block, L. E.; Hansen, L. K.; Dingee, C.; Walters, A.; Rogers, R. D. Chitin-calcium alginate composite fibers for wound care dressings spun from ionic liquid solution. J. Mater. Chem. B 2014, 2, 3924−3936. (39) Cai, J.; Zhang, L.; Liu, S. L.; Liu, Y. T.; Xu, X. J.; Chen, X. M.; Chu, B.; Guo, X. L.; Xu, J.; Cheng, H.; Han, C. C.; Kuga, S. Dynamic self-assembly induced rapid dissolution of cellulose at low temperatures. Macromolecules 2008, 41, 9345−9351. (40) Fang, Y.; Duan, B.; Lu, A.; Liu, M. L.; Liu, H. L.; Xu, X. J.; Zhang, L. N. Intermolecular interaction and the extended wormlike chain conformation of chitin in NaOH/Urea aqueous solution. Biomacromolecules 2015, 16, 1410−1417. (41) Hu, X.; Du, Y.; Tang, Y.; Wang, Q.; Feng, T.; Yang, J.; Kennedy, J. F. Solubility and property of chitin in NaOH/urea aqueous solution. Carbohydr. Polym. 2007, 70, 451−458. (42) Cai, J.; Zhang, L. Rapid dissolution of cellulose in LiOH/Urea and NaOH/Urea aqueous solutions. Macromol. Biosci. 2005, 5, 539− 548. (43) Duan, B.; Chang, C. Y.; Ding, B. B.; Cai, J.; Xu, M.; Feng, S. C.; Ren, J. Z.; Shi, X. W.; Du, Y. M.; Zhang, L. N. High strength films with gas-barrier fabricated from chitin solution dissolved at low temperature. J. Mater. Chem. A 2013, 1, 1867−1874. (44) Duan, B.; Zheng, X.; Xia, Z. X.; Fan, X. L.; Guo, L.; Liu, J. F.; Wang, Y. F.; Ye, Q. F.; Zhang, L. N. Highly biocompatible nanofibrous microspheres self-assembled from chitin in NaOH/Urea aqueous solution as cell carriers. Angew. Chem., Int. Ed. 2015, 54, 5152−5156. (45) Cai, J.; Zhang, L. Unique gelation behavior of cellulose in NaOH/Urea aqueous solution. Biomacromolecules 2006, 7, 183−189. (46) Ding, B.; Cai, J.; Huang, J.; Zhang, L.; Chen, Y.; Shi, X.; Du, Y.; Kuga, S. Facile preparation of robust and biocompatible chitin aerogels. J. Mater. Chem. 2012, 22, 5801−5809. (47) Shen, X.; Shamshina, J. L.; Berton, P.; Gurau, G.; Rogers, R. D. Hydrogels based on cellulose and chitin: Fabrication, properties, and applications. Green Chem. 2016, 18, 53−75. (48) Jang, M. K.; Kong, B. G.; Jeong, Y. I.; Lee, C. H.; Nah, J. W. Physicochemical characterization of alpha-chitin, beta-chitin, and gamma-chitin separated from natural resources. J. Polym. Sci., Part A: Polym. Chem. 2004, 42, 3423−3432. (49) Kaya, M.; Seyyar, O.; Baran, T.; Turkes, T. Bat guano as new and attractive chitin and chitosan source. Front. Zool. 2014, 11, 1−10. (50) Oh, S. Y.; Yoo, D. I.; Shin, Y.; Kim, H. C.; Kim, H. Y.; Chung, Y. S.; Park, W. H.; Youk, J. H. Crystalline structure analysis of cellulose treated with sodium hydroxide and carbon dioxide by means of X-ray diffraction and FTIR spectroscopy. Carbohydr. Res. 2005, 340, 2376− 2391. (51) Zhang, Y. Q.; Xue, C. H.; Xue, Y.; Gao, R. C.; Zhang, X. L. Determination of the degree of deacetylation of chitin and chitosan by X-ray powder diffraction. Carbohydr. Res. 2005, 340, 1914−1917. (52) Higgins, A. M.; Jones, R. A. L. Anisotropic spinodal dewetting as a route to self-assembly of patterned surfaces. Nature 2000, 404, 476− 478. (53) Tsioptsias, C.; Michailof, C.; Stauropoulos, G.; Panayiotou, C. Chitin and carbon aerogels from chitin alcogels. Carbohydr. Polym. 2009, 76, 535−540. (54) Lu, Y.; Sun, Q.; She, X.; Xia, Y.; Liu, Y.; Li, J.; Yang, D. Fabrication and characterization of α-chitin nanofibers and highly transparent chitin films by pulsed ultrasonication. Carbohydr. Polym. 2013, 98, 1497−1504. (55) Tsutsumi, Y.; Koga, H.; Qi, Z. D.; Saito, T.; Isogai, A. Nanofibrillar chitin aerogels as renewable base catalysts. Biomacromolecules 2014, 15, 4314−4319. (56) Zhou, Y.; Fu, S.; Pu, Y.; Pan, S.; Ragauskas, A. J. Preparation of aligned porous chitin nanowhisker foams by directional freeze-casting technique. Carbohydr. Polym. 2014, 112, 277−283. (57) Gavillon, R.; Budtova, T. Aerocellulose: New highly porous cellulose prepared from cellulose-NaOH aqueous solutions. Biomacromolecules 2008, 9, 269−277.

(58) Cai, J.; Kimura, S.; Wada, M.; Kuga, S.; Zhang, L. Cellulose aerogels from aqueous alkali hydroxide-urea solution. ChemSusChem 2008, 1, 149−154. (59) Huang, X.; Brazel, C. S. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J. Controlled Release 2001, 73, 121−136. (60) Bhattarai, N.; Gunn, J.; Zhang, M. Q. Chitosan-based hydrogels for controlled, localized drug delivery. Adv. Drug Delivery Rev. 2010, 62, 83−99.

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Comparison of Hydrogels Prepared with Ionic-Liquid-Isolated vs

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