Biodegradable Polymers from Renewable Sources: Rheological

Biomacromolecules 2005, 6, 684-690

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Biodegradable Polymers from Renewable Sources: Rheological Characterization of Hemicellulose-Based Hydrogels Margaretha So¨derqvist Lindblad,† Ann-Christine Albertsson,*,† Elisabetta Ranucci,‡ Michele Laus,§ and Elena Giani§ KTH Fibre and Polymer Technology, Royal Institute of Technology, Teknikringen 56-58, SE-100 44 Stockholm, Sweden, Dipartimento di Chimica Organica e Industriale, Universita` di Milano, via Venezian 21, 20133 Milano, Italy, and Dipartimento di Scienze e Tecnologie Avanzate, Corso Borsalino 54, Universita` del Piemonte Orientale “A. Avogadro”, INSTM, UdR Alessandria, 15100 Alessandria, Italy Received August 17, 2004; Revised Manuscript Received November 19, 2004

Hemicellulose-based hydrogels were prepared by radical polymerization of 2-hydroxyethyl methacrylate or poly(ethylene glycol) dimethacrylate with oligomeric hydrosoluble hemicellulose modified with well-defined amounts of methacrylic functions. The polymerization reaction was carried out in water at 40 °C using a redox initiator system. The hydrogels were in general elastic, soft, and easily swellable in water. Their viscoelastic properties were determined by oscillatory shear measurements on 2 mm thick hydrogels under a slight compression to avoid slip, over the frequency range 10-1 to 102. The rheological characterization indicated that the elastic response of the hydrogels was stronger than the viscous response, leading to the conclusion that the hydrogel systems displayed a predominantly solidlike behavior. The curves showed an increase in shear storage modulus with increasing cross-linking density. The nature of the synthetic comonomer in the hemicellulose-based hydrogels also influenced the shear storage modulus. Comparison of hemicellulosebased hydrogels with pure poly(2-hydroxyethyl methacrylate) hydrogels showed that their behaviors were rather similar, demonstrating that the synthetic procedure made it possible to prepare hemicellulose-based hydrogels with properties similar to those of pure poly(2-hydroxyethyl methacrylate) hydrogels. Introduction The development of new products and materials from renewable sources is nowadays being viewed as a strategic research area, on the basis of the consideration that the fossil fuels available on earth will be exhausted in the foreseeable future.1-3 Increasing attention is also being devoted to the development of biodegradable/bio-based plastics,4-6 since there is evidence that nondegradable plastics are now a serious worldwide environmental and health concern. According to the classic definition, hemicelluloses are cellwall heterogeneous polysaccharides which are extractable by aqueous alkaline solutions. They constitute 20-30% of the total bulk of annual and perennial plants and are among the most abundant native polymers in the world. Hemicelluloses have so far hardly been utilized for industrial production although they represent an extensive raw material resource. Several authors have proposed different methods of chemically modifying hemicelluloses,7,8 often under drastic conditions. In our previous work, we have already reported on the use of hemicellulose as a natural source for the production of novel biodegradable hydrogels.9 The procedure adopted involved a chemical modification, the methacry* To whom correspondence should be addressed. E-mail: aila@ polymer.kth.se. † Royal Institute of Technology. ‡ Universita ` di Milano. § INSTM.

loylation reaction carried out under mild conditions, of low molecular weight (below 3000) soluble hemicellulose fractions obtained by the steam explosion extraction of spruce wood.10 The main structure of these soluble fractions was O-acetylgalactoglucomannan, characterized by a high degree of acetylation, which leads to a good solubility both in water and in organic solvents and hinders the development of a crystalline order.11 The methacryloylated hemicellulose was transformed into soft hydrogel samples by radical polymerization in the presence of redox initiators. The hemicellulose-based hydrogels obtained by this procedure were hydrated materials, with a potential as biodegradable matrixes. Therefore, they deserved to be considered for applications in strategic areas such as drug release and tissue engineering. However, their mechanical properties were poor, and it was necessary to copolymerize them with a synthetic comonomer, e.g., 2-hydroxyethyl methacrylate (HEMA), or a macromonomer, e.g., methacryloylated poly(ethylene glycol) (PEGDMA), to obtain new mixed natural/ synthetic hydrogels endowed with an optimum hydrophilic/ hydrophobic balance, and suitable mechanical and degradation properties. The main interest in hydrogels is their soft consistency, which derives from their high water content, and their tissuelike behavior, which is due to their specific viscoelastic performance. Dynamic mechanical thermal (DMTA) and rheometric analysis provide powerful tools for the charac-

10.1021/bm049515z CCC: $30.25 © 2005 American Chemical Society Published on Web 01/28/2005

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terization of the viscoelastic behavior of hydrogels, and the results are strictly related to the internal structure, in terms of, e.g., cross-linking density, chain length, and degree of swelling. Several results are presented in the literature dealing with the DMTA characterization of hydrogels and, more recently, with an oscillatory shear rheological analysis, which is also suitable for monitoring the long-term degradation of hydrogels.12-17 In this paper we report the oscillatory shear rheological characterization of a series of PHEMA/hemicellulose- and PEG/hemicellulose-based hydrogels obtained from hemicelluloses with different methacryloylation degrees compared with that of PHEMA hydrogels prepared by conventional procedures. Experimental Section Materials and Methods. (1) Reagents and Solvents. 2-Hydroxyethyl methacrylate (HEMA), g99% (Fluka), ethylene glycol dimethacrylate (EGDMA), 98% (Aldrich), poly(ethylene glycol-600) dimethacrylate (PEGDMA), molecular weight ca. 875 (Aldrich), N,N′-carbonyldiimidazole (CDI), 97% (Lancaster), triethylamine (NEt3), g99.5% (Fluka), chloroform, 99+%, anhydrous, stabilized with amylenes (Aldrich), ethyl acetate, 99.8% (Lab Scan), dimethyl sulfoxide (DMSO), 99.5% (Lab Scan), ammonium peroxodisulfate, g98.0% (Fluka), sodium pyrosulfite, g98.0% (Fluka), and DMSO-d6, g99.8 atom % D (unit 1a, Bingswood Industrial Estate) were used as received unless otherwise stated. (2) Hemicellulose from Spruce. The hemicellulose fraction used for hydrogel synthesis was produced according to a procedure developed elsewhere.10 Water-impregnated chips (2-10 mm) (Picea abies) were treated with saturated steam at 200 °C for 2 min. By this steam explosion treatment, wood chips were separated into a water-soluble and a waterinsoluble fraction. Hemicelluloses present in the watersoluble fraction were purified by filtration through a 0.2 µm filter and by preparative size exclusion chromatography (SEC) (Index 50 column filled with Superdex 30 preparative grade, Amersham Pharmacia Biotech, flow rate 12 mL/min, height of the filtration bed 29 cm, and diameter 10 cm) using water as the eluent. After evaporation the eluate was freezedried and the hemicelluloses were recovered as a white and fluffy solid with a dry matter content of ca. 90%. The carbohydrate composition was determined by enzymatic hydrolysis and subsequent capillary zone electrophoresis,18 the molecular weight was determined by analytical SEC, which was calibrated with fractionated O-acetyl-galactoglucomannan standards characterized by matrix-assisted laser desorption ionization time-of-flight mass spectrometry,19 and the degree of acetylation was determined by 1H NMR.11 (3) Synthesis of 2-[(1-Imidazolyl)formyloxy]ethyl Methacrylate. 2-[(1-Imidazolyl)formyloxy]ethyl methacrylate (HEMA-Im) was prepared by treating HEMA with CDI in chloroform solution at room temperature as described elsewhere.20 1H NMR (DMSO-d6): δ ) 1.86 (s, 3H, CH3), 4.47, 4.62 (m, 4H, CH2O), 5.70, 6.04 (s, 1H each, vinyl CH), 7.08, 7.58, 8.25 (s, 1H each, heteroatomic CH).

Table 1. Hemicellulose-Based Hydrogelsa code

degree of modification in hemicellulose, %

synthetic comonomer

18HEMA 25HEMA 25PEG 32HEMA

18 25 25 32

HEMA HEMA PEGDMA HEMA

a For all hemicellulose-based hydrogels the composition of the reactive mixture was 0.5/0.5/1.1 hemicellulose/synthetic comonomer/water in weight relative amounts.

Table 2. Composition of the Reactive Mixture in Preparation of PHEMA Hydrogels code

HEMA/EGDMA/water weight relative amounts

0 high 2 high 4 high 2 low

1.0/0.00/1.1 1.0/0.02/1.1 1.0/0.04/1.1 1.0/0.02/0.5

(4) Modification of Hemicelluloses for Hydrogel Synthesis. Three different batches of modified hemicellulose were prepared. Typical conditions were as follows: Hemicellulose (3.0 g, absolutely dry, 18 mmol with respect to the repeating unit) was dissolved in DMSO (76 mL), and HEMA-Im (4.5 g, 20 mmol) was added. Triethylamine (405 mg, 4.0 mmol) was added as catalyst, and the reaction mixture was maintained for 2-5 h at 45 °C under stirring. The product was precipitated twice in ethyl acetate as light brown crystals, and the solvent was poured off. Eventually, the product was dried under vacuum for about 20 h. The degree of modification, analyzed by 1H NMR, was 18-32%. Yield: 88-95%. 1H NMR (DMSO-d6): δ ) 1.88 (s, 3 H, CH3), 2.0-2.1 (s, 3 H, CH3CO, acetyl in hemicellulose), 4.31 (m, 4 H, CH2O), 5.70, 6.06 (s, 1 H, each vinyl CH). (5) Hemicellulose/HEMA Hydrogel Synthesis. Hemicellulose-based hydrogels with different compositions were prepared; see Table 1. Typical conditions were as follows: Modified hemicellulose (500 mg) and HEMA (500 mg) were polymerized in water (1100 mg) using a mixture of ammonium peroxodisulfate (1.0 mg) and sodium pyrosulfite (1.0 mg) as the radical initiator system. The polymerizing solution was first injected into a circular mold (diameter 28 mm) with a thickness of 2 mm, and it was then heated to 40 °C and finally maintained at this temperature for 180 min. (6) Hemicellulose/PEG Hydrogel Synthesis. A hemicellulose-based hydrogel was prepared; see Table 1. The conditions were as follows: Modified hemicellulose (500 mg) and PEGDMA (500 mg) were polymerized in water (1100 mg) using a mixture of ammonium peroxodisulfate (1.0 mg) and sodium pyrosulfite (1.0 mg) as the radical initiator system. The polymerizing solution was first injected into a circular mold (diameter 28 mm) with a thickness of 2 mm, and it was then heated to 40 °C and finally maintained at this temperature for 180 min. (7) PHEMA Hydrogel Synthesis. PHEMA hydrogels with different compositions were prepared; see Table 2. Typical conditions were as follows: EGDMA (0.10 g) dissolved in HEMA (5.0 g) was polymerized in water (2.5 g) using a mixture of ammonium peroxodisulfate (5.0 mg)

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and sodium pyrosulfite (5.0 mg) as the radical initiator system. The polymerizing solution was first injected into circular molds (diameter 28 mm) with a thickness of 2 mm, and it was then heated to 40 °C and finally maintained at this temperature for 180 min. (8) Swelling. Swelling tests were performed by drying 200-400 mg of hydrogel, swollen in an abundant amount of deionized water (pH 7.0), at 105 °C. The swelling of the material was calculated from the weight of the material before and after drying: swelling ratio (%) ) (Ws - Wd)/Wd where Ws and Wd are the weights of the samples in the swollen state and after drying, respectively. Instruments. (1) Nuclear Magnetic Resonance Spectrometry. 1H NMR spectra were recorded at 400 MHz on a Bruker Avance 400, using Bruker software. Samples of precipitated modified hemicelluloses (ca. 25 mg) were dissolved in deuterated DMSO (ca. 0.8 mL) in sample tubes 5 mm in diameter. Nondeuterated DMSO (δ ) 2.50) was used as the internal standard. (2) Rheometry. Viscoelastic measurements were performed using a strain-controlled rheometer (Rheometric Scientific ARES). Samples were prepared in the form of disks with a diameter of 28 mm and a thickness of 2.3 mm (swollen state). Samples were tested using a parallel plate geometry with a diameter of 25 mm. The samples were placed between the rheometer plates, and a slight compressive force of about 50 g was applied. A strain sweep test was then conducted at 30 °C on each sample with a frequency of 1 Hz and deformations in the range from 0.05% to 15%. The frequency sweep test was conducted with a strain of 0.2% from 0.1 to 16 Hz at 30 °C. Results and Discussion Fractionation of Spruce and Characterization of the Hemicellulose Fraction. The hemicellulose fraction used for the hydrogel synthesis, soluble in both water and DMSO, was produced according to a procedure described elsewhere,10 based on the steam explosion of spruce chips. The whole procedure gave a yield of approximately 30%, with respect to the total amount of hemicelluloses in spruce, after heat treatment at 200 °C for 2 min. Analysis showed that 80% of the hemicellulose fraction was O-acetylgalactoglucomannan (galactose/glucose/mannose ) 15/29/100) and that the rest was other polysaccharides, mainly arabino-4-Omethylglucuronoxylan. The molecular weight of the hemicellulose fraction ranged from 500 to 13 000 (corresponding to 3-80 anhydroglucose units per oligomer). The numberaverage molecular weight and polydispersity of the Oacetylgalactoglucomannan were 2500 and 1.7, respectively. The approximate degree of acetylation of the O-acetylgalactoglucomannan was 0.3. The 1H NMR spectrum showed that the hemicellulose fraction contained traces of aromatic compounds. Modification of Hemicellulose and Hydrogel Synthesis. Hemicellulose was modified with methacrylic functions according to a previously reported procedure,9 involving the

Figure 1. Synthetic pathway for modification of hemicellulose with HEMA-Im.

Figure 2. Pathway for synthesis of a hemicellulose-based hydrogel.

reaction with HEMA-Im in DMSO at 45 °C in the presence of triethylamine as catalyst. The synthetic pathway followed is shown in Figure 1. HEMA-Im was in turn prepared by the reaction of HEMA with CDI in chloroform. The specific benefits of this experimental procedure are its facility, superior stability, and relative insensitivity to traces of moisture, and its compatibility with most solvents. Moreover, it contains a leaving group, imidazole, which is neither harmful nor chemically aggressive toward hemicellulose. The degree of modification was evaluated by 1H NMR spectroscopy. Modified hemicelluloses with different degrees of modification, defined as the number of methacryloylated hydroxyl groups in relation to the total amount of anhydroglucose units, ranging between 18% and 32%, were prepared, as reported in Table 1. Hemicellulose-based hydrogels (see Figure 2) were prepared by dissolving the reactive modified hemicellulose in water and then adding the synthetic comonomer HEMA or PEGDMA (see Table 1). The cross-linking reaction was a conventional radical copolymerization carried out at 40 °C in the presence of a redox initiator, a mixture of ammonium peroxodisulfate and sodium pyrosulfite. The curing reaction was carried out in a glass mold and led to a thin and soft membrane, which easily swelled in water. A schematic representation of a methacryloylated hemicellulose and a hemicellulose-based hydrogel is shown in Figure 3. A higher hemicellulose content than used in this work could be used, and in fact, whole hemicellulose hydrogels have been



Figure 4. Pathway for synthesis of a PHEMA hydrogel. Table 3. Swelling of Hemicellulose-Based and PHEMA Hydrogels

Figure 3. Schematic representation of methacryloylated hemicellulose (a, top) and a hemicellulose-based hydrogel (b, bottom). The chair conformation denotes an anhydroglucose unit in the hemicellulose. Polymerizable methacrylate groups are denoted with a double bond (a). Polymerized methacrylate groups and comonomers are denoted with bold lines (b).

prepared. However, high concentrations of modified hemicellulose prepolymers yielded large amounts of polymerization heat. This made polymerization very fast and reaction control difficult and led often to uneven hydrogel samples. The high reactivity of modified hemicellulose is not surprising, and it can be ascribed to the high concentration of reactive groups in hemicellulose chains. The high purity of modified hemicellulose also played its role. It was necessary to use larger amounts of water in the case of hemicellulosebased hydrogels than in the case of PHEMA ones. This was due to the relatively high viscosity of modified hemicellulose aqueous solutions, which made it necessary to increase the water content to improve workability.

code

swelling ratio, %

code

swelling ratio, %

25HEMA 25PEG 32HEMA

167 187 168

2 high 4 high 2 low

83 84 68

PHEMA hydrogels (see Figure 4) were prepared by first dissolving EGDMA in HEMA, adding water in desired amounts, and finally adding the redox initiator, a mixture of ammonium peroxodisulfate and sodium pyrosulfite; see Table 2. PHEMA hydrogels were prepared with both a normal water content (0.5 weight relative amount) and a high water content (1.1 weight relative amount), which is the same amount of water as is needed for the preparation of hemicellulose-based hydrogels. Soft and transparent hydrogels were obtained, which swelled easily in water at room temperature. Swelling Ratio. A knowledge of the swelling behavior of the hydrogels is important, especially in view of their applications in the biomedical field. Swelling ratios are given in Table 3. In general, the hemicellulose-based hydrogels had much higher swelling ratios than the PHEMA hydrogels, 167-187% and 68-84%, respectively. This was expected and was due to the high amount of hydroxyl groups in the hemicellulose. However, there was no significant difference in swelling ratio when modified hemicelluloses with different degrees of modification were used, 167% and 168%. When PEGDMA was used as the synthetic comonomer, the swelling ratio was slightly higher than when HEMA was used as the synthetic comonomer, 187% and 167-168%, respectively. This was an expected result since PEG is a far more hydrophilic monomer than HEMA. The PHEMA hydrogels prepared with more water had, as expected, slightly higher swelling ratios than the PHEMA hydrogels prepared with a normal amount of water, 83-84% and 68%, respectively. There was no significant difference in swelling ratio between PHEMA hydrogels prepared with different amounts of cross-linker, 83% and 84%. Dynamic Mechanical Characterization of Hydrogels. The dynamic mechanical characterization is useful for understanding the structure of the hydrogels and consequently their possible applications. Samples were first subjected to a strain sweep test in which they were deformed at different shear strains, and the moduli were recorded to define the linear viscoelastic zone in which the modulus G′ is independent of the applied strain. A deformation of 0.2% was chosen in the subsequent tests to ensure that each measurement was made in the linear viscoelastic region. Each sample

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Figure 6. Storage shear modulus at 1 Hz and 30 °C versus content of the cross-linker: [, water in 1.1 weight relative amount; 9, water in 0.5 weight relative amount. The data are average values from two or three samples; error bars ) 1 standard deviation.

Figure 5. Storage shear and loss shear moduli of a PHEMA hydrogel with EGDMA as cross-linker in 0.02 weight relative amount and water in 1.1 weight relative amount (a, top) and a hemicellulose-based hydrogel with a 32% degree of modification and HEMA as comonomer (b, bottom) as a function of frequency at 30 °C.

was then subjected to a frequency sweep test. A sinusoidal deformation of constant peak amplitude was applied over the range of frequencies from 0.1 to 16 Hz. The frequency sweep test generated frequencies which were logarithmically incremented, and one measurement was taken at each frequency. Figure 5 presents the results of the frequency sweep test of a PHEMA hydrogel prepared with EGDMA as crosslinker in 0.02 weight relative amount and water in 1.1 weight relative amount and a hemicellulose-based hydrogel with a 32% degree of modification and HEMA as comonomer. The storage shear modulus, G′, is higher than the loss shear modulus, G′′, over the entire frequency region for both hydrogels. This indicates that the elastic response of the material is stronger than the viscous response. As this trend is common for all the samples, we can conclude that the present hydrogel system displays a predominantly solidlike behavior. The elastic modulus is fairly constant throughout the entire frequency region, although a slight decrease is observed with decreasing frequency. Several PHEMA hydrogels were prepared for comparison. The experimental parameters considered were the contents

of cross-linker and water. Figure 6 shows G′ as a function of cross-linker content. G′ increased with increasing amount of cross-linker. Similar results have been reported in other hydrogel systems.12,13 Figure 6 also shows G′ for a reference PHEMA hydrogel prepared with a normal content of water, 0.5 weight relative amount. It is evident that the different weight relative amounts of water used in hydrogel synthesis did not significantly influence the G′ of the hydrogel. In fact, the content of water in the hydrogels prepared with different amounts of water did not vary very much. PHEMA hydrogels prepared with a 0.5 weight relative water amount contained 40% water after swelling in deionized water, while PHEMA hydrogels prepared with a 1.1 weight relative water amount contained 45% water. The difference in water content is then small in the swollen hydrogels. In drug release applications, it is important to have access to hydrogels with different cross-linking densities since the cross-linking density influences the rate of drug release.21 In fact, a higher degree of modification means a greater methacrylic functional group density and consequently a higher cross-linking density in the final network. To elucidate this, hemicellulose-based hydrogels starting from hemicellulose with different degrees of modification (18%, 25%, and 32%) were prepared, and their dynamic mechanical behavior was examined. Figure 7 shows the storage shear modulus versus frequency for these hydrogels. The hemicellulose-based hydrogel prepared from modified hemicellulose with a 32% degree of modification had the highest storage shear modulus, as expected. However, the hydrogels prepared from modified hemicellulose with 18% and 25% degrees of modification had almost the same storage shear modulus. In addition, two synthetic comonomers, HEMA and PEGDMA, were used to obtain hydrogels with different degrees of hydrophilicity. Hemicellulose with a 25% degree of modification was reacted with both HEMA and PEGDMA. Figure 8 shows the storage shear modulus plotted versus


Figure 7. Storage shear modulus at 30 °C versus frequency for hemicellulose-based hydrogels with HEMA as synthetic comonomer: blue, hemicellulose with a 32% degree of modification; green, hemicellulose with a 25% degree of modification; red, hemicellulose with an 18% degree of modification.


Figure 9. Storage shear modulus at 30 °C versus frequency for a hydrogel prepared from HEMA (green, EGDMA in 0.02 weight relative amount and water in 0.5 weight relative amount) and a hemicellulosebased hydrogel (blue, hemicellulose with a 32% degree of modification and HEMA as synthetic copolymer).

Conclusions

Figure 8. Storage shear modulus at 30 °C versus frequency for hemicellulose-based hydrogels (hemicellulose with a 25% degree of modification) with different synthetic comonomers: blue, methacryloylated PEG as synthetic comonomer; green, HEMA as synthetic comonomer.

frequency for these hydrogels. Hemicellulose-based hydrogels with PEGDMA in 0.5 weight relative amount showed a higher modulus than hydrogels with HEMA in 0.5 weight relative amount. This effect is clearly due to the fact that PEGDMA oligomers can react at both chain ends, while HEMA is a monofunctional monomer (Figure 4). The reactivity of both chain ends in PEGDMA can give a substantial contribution to the overall cross-linking density. A comparison can also be made between the hemicellulose-based and the pure PHEMA hydrogels. Figure 9 illustrates the trend of the storage shear modulus as a function of the frequency for a PHEMA hydrogel made with a normal content of water and cross-linker in 0.02 weight relative amount and a hemicellulose-based hydrogel with a 32% degree of modification. Although direct comparison is quite difficult due to inherent structural differences, it appears that by appropriately adjusting the experimental parameters it is possible to prepare hemicellulose-based hydrogels with properties similar to those of the PHEMA hydrogels.

The results reported in this paper demonstrate that products obtained from renewable sources are suitable for the preparation of novel polymeric structures having potential applications as specialty polymers. Soluble low molecular weight hemicelluloses, obtained by steam explosion of spruce chips, were modified by the incorporation of methacrylic functional groups. A variety of methacryloylated hemicellulose samples with different contents of methacrylic groups were prepared and subsequently employed to obtain mixed hydrophilic/ hydrophobic hydrogels with HEMA and PEG methacrylate. A close comparison of the dynamic mechanical curves demonstrated that the main parameter affecting the mechanical response is the degree of cross-linking, which can be controlled by adjusting the parameters involved in the preparation of the hydrogels, and the nature of the comonomers. The hemicellulose-based hydrogels have physicomechanical properties comparable to those of PHEMA hydrogels. This is of special interest because it opens up the possibility of using these novel hydrogels as an interesting alternative to those which are normally used. Acknowledgment. Financial support from VINNOVA (PROFYT program) is gratefully acknowledged. We thank Guido Zacchi and Magnus Palm for performing the steam explosion treatment and for help with SEC separation. Olof Dahlman, Anna Jacobs, and Anita Teleman are gratefully thanked for characterization of the hemicellulose fraction using CZE, SEC/MALDI-TOF mass spectrometry, and 1H NMR. References and Notes (1) So¨derqvist Lindblad, M.; Liu, Y.; Albertsson, A.-C.; Ranucci, E.; Karlsson, S. AdV. Polym. Sci. 2002, 157, 139. (2) Narayan, R. In Emerging technologies for materials and chemicals for biomass; Rowell, R. M., Schultz, T. P., Narayan, R., Eds.; ACS Symp. Ser.; American Chemical Society: Washington, DC, 1992; Vol 476, pp 1-10. (3) Zeng, A.-P.; Biebl, H. AdV. Biochem. Eng./Biotechnol. 2002, 74, 239. (4) Stevens, E. S. Green plastics: An introduction to the new science of biodegradable plastics; Princeton University Press: Princeton, NJ, 2002.

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(5) Albertsson, A.-C.; Karlsson, S. In ComprehensiVe polymer science, first supplement; Allen, G., Aggarwal, S. L., Russo, S., Eds.; Pergamon Press: Oxford, 1992; p 285-297. (6) Patel, M.; Bastioli, C.; Marini, L.; Wu¨rdinger, E. In Biopolymers; Steinbu¨chel, A., Ed.; Wiley-VCH: Weinheim, Germany, 2003; Vol. 10, p 409-452. (7) So¨derqvist Lindblad, M.; Albertsson, A.-C. In Polysaccharides: Structural diVersity and functional Versatility; Dumitriu, S., Ed.; Marcel Dekker: New York, 2004; pp 491-508. (8) Heinze, T.; Koschella, A.; Ebringerova´, A. In Hemicelluloses: Science and Technology; Gatenholm, P., Tenkanen, M., Eds.; ACS Symp. Ser.; American Chemical Society: Washington, DC, 2004; Vol. 864, pp 312-325. (9) So¨derqvist Lindblad, M.; Ranucci, E.; Albertsson, A.-C. Macromol. Rapid Commun. 2001, 22, 962. (10) Palm, M.; Zacchi, G. Biomacromolecules 2003, 4, 617. (11) Lundqvist, J.; Teleman, A.; Junel, L.; Zacchi, G.; Dahlman, O.; Tjerneld, F.; Stålbrand, H. Carbohydr. Polym. 2002, 48, 29. (12) Anseth, K. S.; Bowman, C. N.; Brannon-Peppas, L. Biomaterials 1996, 17, 1647.

So¨derqvist Lindblad et al. (13) Trompette, J. L.; Fabre`gue, E.; Cassanas, G. J. Polym. Sci., Part B: Polym. Phys. 1997, 35, 2535. (14) Dentini, M.; Desideri, P.; Crescenzi, V.; Yuguchi, Y.; Urakawa, H.; Kajiwara, K. Macromolecules 2001, 34, 1449. (15) Jones, D. S. Int. J. Pharm. 1999, 179, 167. (16) Kjøniksen, A.-L.; Nystro¨m, B. Macromolecules 1996, 29, 5215. (17) Meyvis, T. K. L.; Stubbe, B. G.; Van Steenbergen, M. J.; Hennink, W. E.; De Smedt, S. C.; Demeester, J. Int. J. Pharm. 2002, 244, 163. (18) Dahlman, O.; Jacobs, A.; Liljenberg, A.; Olsson, A. I. J. Chromatogr. A 2000, 891, 157. (19) Jacobs, A.; Dahlman, O. Biomacromolecules 2001, 2, 894. (20) Ranucci, E.; Spagnoli, G.; Ferruti, P. Macromol. Rapid Commun. 1999, 20, 1. (21) Hennink, W. E.; Talsma, H.; Borchert, J. C. H.; De Smedt, S. C.; Demeester, J. J. Controlled Release 1996, 39, 47.

BM049515Z

Biodegradable Polymers from Renewable Sources: Rheological

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