Research Article

Received: 23 June 2008, Revised: 18 August 2008, Accepted: 28 August 2008, Published online in Wiley InterScience: 17 December 2008

(www.interscience.wiley.com) DOI: 10.1002/pat.1299

Photopolymerization of alicyclic methacrylatehydrogels for controlled release

Jing Hana, Yong Hea, Ming Xiaoa, Guiping Maa and Jun Niea*

Alicyclic hydroxy methacrylate monomer, o-hydroxy

Polym. Adv

cyclohexyl methacrylate (HCMA), was synthesized and charac-terized by Fourier transformed infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance spectroscopy(1H-NMR). Photopolymerization kinetics of HCMA was investigated via real-time infrared spectroscopy (RT-IR).Polymeric network hydrogels based on hydroxyethyl methacrylate (HEMA) and HCMA were prepared by usingthe photopolymerization technique. Mechanical strength, swelling characteristic, and controlled release behavior ofhydrogels with various feed compositions were studied. Poly(HEMA-co-HCMA) hydrogel had higher storage modulusthan that of poly(HEMA) hydrogel as investigated by dynamic mechanical analysis (DMA). Acid orange 8 was used as amodel drug for the investigation of drug release behavior of copolymeric hydrogels. Results indicated that increase inHCMA ratio in hydrogel composition could reduce the swelling rate and prolong the release time. Scanning electronmicroscopy (SEM) was also utilized to study the surfacemorphology of hydrogels, and the results indicated that HCMAcontent influenced pore diameter on the hydrogel surface. Copyright � 2008 John Wiley & Sons, Ltd.

Keywords: hydrogel; controlled release; photopolymerization; kinetics

* Correspondence to: J. Nie, State Key Lab of Chemical Resource Engineering,

The Key Laboratory of Beijing City on Preparation and Processing of Novel

Polymer Materials, Beijing University of Chemical Technology, Beijing 100029,

P. R. China.

E-mail: niejun@mail.buct.edu.cn

a J. Han, Y. He, M. Xiao, G. Ma, J. Nie

State Key Lab of Chemical Resource Engineering, The Key Laboratory of

Beijing City on Preparation and Processing of Novel Polymer Materials, Beijing

University of Chemical Technology, Beijing 100029, P. R. China 6

INTRODUCTION

Hydrogels, three-dimensional networks of hydrophilic polymers,can swell in water and hold large amounts while maintainingtheir structure. Hydrogels have excellent biocompatibility,permeability, and physical characteristics; in particular, theyresemble living tissues closely in their physical properties andhave therefore been applied inmany biomedical fields as scaffoldmaterials,[1–4] drug delivery systems[5–8] and barriers.[9–10]

However, the properties of hydrogels as drug carriers shouldbe improved in many aspects, including mechanical property,degradation rate, regulation possibility of controlled releasebehavior, and preparation method. Many strategies have beendeveloped to solve these problems, such as copolymerization,preparation of interpenetrating polymer network (IPN) orsemi-interpenetrating polymer network (semi-IPN) hydrogels,and composite hydrogels.Copolymerization has been widely applied to alter hydrogel

properties. Hydrophilic monomer copolymerized with rigidmonomers such as methyl methacrylate (MMA) and styreneaiming to improve hydrogel mechanical strength.[11] It wasreported that HEMA copolymerized with various cyclic mono-mers derived from cis- and trans- 1,2-dihydroxycyclohexa-3,5-diene to enhance the mechanical strength of the hydrogelmaterials.[12] Another generally used approach to regulatehydrogel properties was to prepare interpenetrating polymernetwork (IPN) or semi-interpenetrating polymer network (semi-IPN) hydrogels. It was found that IPN formation dramaticallyincreased the mechanical strength compared to copolymerichydrogel of similar water content.[13] IPN and semi-IPN structurehydrogels not only hold high mechanical strength but alsocombine properties of each network.[14–16] Many researches werecarried out on IPN and semi-IPN hydrogels as drug carriers, andthe results were promising.[17–19] Recently, Gong et al. obtained

. Technol. 2009, 20 607–612 Copyright �

novel structure hydrogel called double-network hydrogel withextremely high mechanical strength, in which the first networkwas highly crosslinked whereas the second network was looselycrosslinked.[20–21] Besides, the preparation of composite hydro-gels such as hydrogel/clay composite, organic/inorganic nano-composite hydrogel was also a promising approach to improvethe properties of hydrogel including mechanical strength andswelling behavior.[22,23]

Among these strategies, copolymerization was the simplestapproach to change hydrogel microstructure and variousproperties. The aim of the present work is to improve hydrogelmechanical strength and alter swelling and controlled releasecharacteristics by copolymerizing hydrophilic monomer withrigid hydrophobic monomer. In our research, alicyclic hydroxymethacrylate monomer, o-hydroxycyclohexyl methacrylate(HCMA), was synthesized. Photopolymerization kinetics of HCMAwas also studied using real-time near infrared spectroscopy(RT-IR). HCMA, bearing rigid hydrophobic cyclohexyl group andhydrophilic hydroxyl group, was added into poly(HEMA) hydrogelcomposition aiming to improve hydrogel properties. Themechanical strength, swelling behavior, and controlled releaseproperty of poly(HEMA-co-HCMA) hydrogels were investigatedcompared with poly(HEMA) hydrogel. The surface morphology of

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hydrogels was characterized by scanning electron microscopy(SEM).

EXPERIMENTAL

Materials

2-Hydroxyethyl methacrylate (HEMA) andmethacrylic acid (MAA)were purchased from Beijing Chemical Reagents Company(China), distilled under reduced pressure in the presence ofhydroquinone, and stored at 48C until use. Cyclohexene oxide(CHO) was supplied by Yueyang Changde Chemicals Industry Co.(China), purified by distillation under reduced pressure. Triethyl-benzylammonium (TEBA) was obtained from Jintan XinanChemical Institute (China) and used without further purification.Photoinitiator Irgacure651 (2,2-Dimethoxy-1,2-diphenylethan-1-one, (Runtec Chemical Co.), Irgacure2959 (1-[4-(2-Hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one, Ciba-Geigy ChemicalCo.) and crosslinker N,N’-methylenebisacrylamide (MBAA, TianjinFuchen Chemicals Reagent Factory), model drug acid orange 8(AO8, Sigma Chemical Co.) and other reagents were used withoutfurther purification.

Synthesis of o-hydroxycyclohexyl methacrylate (HCMA)

HCMA was synthesized by the reaction of cyclohexene oxide(CHO) with methacrylic acid (MAA) in the presence oftriethylbenzylammonium (TEBA) as a catalyst and hydroquinoneas a polymerization inhibitor. In brief, CHO (49.07 g, 0.5mol) andhydroquinone (0.05 g) were put into 250mL four-necked roundbottom flask equipped with a thermometer, a condenser, adropping funnel, and amechanical stirrer. The flask was kept in oilbath at a temperature of 758C while MAA (43.04 g, 0.5mol)containing TEAB (0.5 g) was added drop wise into the solution viaa dropping funnel for about 2 hr. The reaction mixture was stirredat 908C for 2 hr and then at 1008C for 1 hr. The crude product waspurified by distillation under reduced pressure to obtain colorlessHCMA. Yield was about 42%. The pure HCMA was characterizedby Fourier transform infrared spectrum (Nicolet Spectra 5700spectrometer, Nicolet Instrument, Thermo Company, Madison,USA) and 1H-NMR spectrum (Bruker AV 600 spectrometer, Bruker,Rheinstetten, Germany).

Photopolymerization study of HCMA

The photopolymerization profiles of HCMA and HEMA wererecorded by real time near-FTIR (Nicolet 5700 Fourier TransformInfrared Spectrometer) via determining the extent of polymeri-zation of methacrylate by measuring the decline of C––Cabsorbance peak area from 6101 to 6234 cm�1 with the increasein irradiation time. The FTIR Spectrometer was modified by

Table 1. Feed compositions of hydrogels

Sample codes S1

HCMA/HEMA (mol ratio) 0/102959 (wt% based on monomer weight) 1MBAA (MBAA/monomer mol ratio) 1/200Deionized water (wt% based on the solution) 40

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designing a horizontal transmission unit for preventing sampleflow during experiment. The mixture of monomer and certainconcentration photoinitiator was injected into a mold made bytwo glass plates equipped with spacers 10� 1mm in diameterand 1.2� 0.1mm in thickness. Samples were exposed to UV-lightspot source (EXFO Lite, with 320–480 nm filter and 5mm crystaloptical fiber, Canada) at room temperature with a light intensityof 10mWcm�2. For each sample, the series FTIR runs wererepeated three times, and the error on calculated double bondconversion as a function of irradiation time was less than 2%. Thedouble bond conversion was calculated by the followingequation.

Double bond conversion ð%Þ ¼ ð1� At

A0Þ � 100

where A0 is the absorbance peak area before irradiation and At isthe absorbance peak area at time t.

Preparation of hydrogels via photopolymerization

Hydrogels were prepared by free radical photopolymerization.The compositions of hydrogels are summarized in Table 1.Various composition solutions were injected into a moldconsisting of two glass slides and spacers with 12� 1mm inthe diameter and 1.2� 0.1mm in thickness. Samples wereexposed to UV-light source as described above with a lightintensity of 30mWcm�2 at room temperature for 15min. Theresultant hydrogels were put into distilled water to leach outresidue monomers and other chemicals at 378C for at least 240 hr.During this period, the water was replaced every 24 hr.

Mechanical property

Hydrogels were cut into strips (width¼ 6mm, thickness¼1.2mm) in their equilibrium swollen state. The mechanicalproperty of hydrogels was measured by dynamic mechanicalanalysis (DMA) (DMTA-V, Rheometyic, USA), operating in thetensile-testingmode. The scans were performed at a frequency of1 Hz, a ramp of 58Cmin�1 from �100 to 1008C.

Swelling behavior measurement of hydrogels

The swelling behaviors of hydrogels were measured gravime-trically. The vacuum-dried hydrogel disk samples were put intodistilled water at 378C. At designed time points, the samples weretaken out and carefully wiped with filter paper to remove theexcess water before being weighed. The percentage of swellingwas calculated by the following formula.

Swelling ð%Þ ¼ ðWs �WdÞWd

� �� 100

S2 S3 S4 S5

1/9 1/8 1/7 1/61 1 1 1

1/200 1/200 1/200 1/20040 40 40 40

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Figure 2. Comparison of photopolymerization of HEMA and HCMA.

PHOTOPOLYMERIZATION OF ALICYCLIC METHACRYLATE

where Wd is the weight of dry hydrogel, and Ws is the weight ofswelling hydrogel at determined time.

Controlled release behavior

Acid orange 8 (AO8) as a model compound was added into thesolution at 0.2wt%. The hydrogels loaded with AO8 wereprepared by the same method as mentioned above but with alonger irradiation time of 30min due to the light absorption ofAO8 which influenced the photopolymerization process andgelation time. Photopolymerized hydrogel disks were placed intoa vial containing 10mL distilled water at 378C in a constanttemperature shaking incubator. At designed time points, 3mLsolution was taken out to monitor UV absorption using a UV-Visspectrophotometer (UV3010, Hitachi Company, Japan) at 490 nmand then calculate the release quantity from a calibration curvederived from the absorbance of the known concentrations ofAO8. The fresh distilled water was added into the vial to keep thesame solution volume. The cumulative percentage release atcertain time t was obtained by the following equation.

Cumulative release ð%Þ ¼ Mt

M1

� �� 100

where Mt is the cumulative release quantity of AO8 at time t, andM1 is the initial loaded quantity of AO8.

Scanning electron microscopy (SEM) observation

Themorphology of hydrogels was observed by scanning electronmicroscope (Hitachi S-4700, Hitachi Company, Japan). Thehydrogel samples were immersed in distilled water at roomtemperature for 240 hr to reach equilibrium state. Then theequilibrated swollen hydrogel samples were freeze-dried in aFreeze Drier under vacuum at �508C for 3 days to remove water.Before observation, the freeze-dried samples were fixed on stubsand sputter coated with gold.

RESULTS AND DISCUSSION

Synthesis of HCMA

HCMA was synthesized through ring-opening reaction fromcyclohexene oxide and methacrylic acid, as illustrated in Fig. 1.The product was characterized by FTIR and 1H-NMR.IR(KBr, cm�1): 3445.8(O-H), 2934.5(C-H), 2861.8(C-H), 1713.2

(C––O), 1635.8(C––C).1H-NMR (CDCl3, d, ppm): 6.11(s,1H,CH––C),

5.57(s,1H,CH––C), 4.61–4.65(m,1H, CH-OH), 3.59–3.63(m,1H,CH-C––O),1.94(s,3H,CH3), 1.71–1.72(d,2H,CH2-CH-OH), 1.24–1.38(m,6H,CH2).

Photopolymerization kinetics

Alicyclic methacrylate monomer was utilized as a comonomer toimprove hydrogel mechanical strength and change swelling

Figure 1. Synthesis scheme of o-h

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property; thus it was necessary to investigate the polymerizationactivity of monomer. Figure 2 shows the double bond conversionversus irradiation time curves of HEMA and HCMA with the sameIrgacure651 concentration (0.5wt%) exposed to UV light(320–480 nm, 10mWcm�2). It was observed that HCMA photo-polymerized more rapidly, but the final double bond conversion(68%) was lower than that of HEMA (89%). The rigid cyclohexylring in HCMAmolecule was the reason for high reactivity, leadingto earlier auto-accelerated time and an earlier gel point formationwhich caused lower final conversion.Further, the effect of photoinitiator Irgacure2959 concentration

on the photopolymerization of HCMA (light intensity¼10mWcm�2) is shown in Fig. 3. The results indicated thatvarying Irgacure 2959 concentration from 0.25 to 2wt%, the finaldouble bond conversion increased from 58 to 64%. However, thedifference between 1 and 2wt% curves was small. Besides,photoinitiator concentration influenced polymerization rate, asreported in many research papers.[24–26] High concentrationphotoinitiator produced more free radicals to initiate polymeri-zation when exposed to UV light; thus the polymerization ratewas higher. Although Irgacure2959 was not the most effectivephotoinitiator, it was selected in hydrogel composition forconsidering its good solubility in water and low cell toxicity.[27]

Mechanical property of hydrogels

The DMA curves of poly(HEMA-co-HCMA) and poly(HEMA)hydrogel are shown in Fig. 4. The trends of both curves werealmost the same: at low temperature the storage modulus ofhydrogels was at high magnitude and decreased gradually withincrease in temperature; when the temperature approached 08C,the storage modulus declined sharply and then decreasedslightly in higher temperature range. In low temperature, water in

ydroxycyclohexyl methacrylate.

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Figure 3. Effect of Irgacure2959 concentration on the photopolymer-

ization of HCMA.Figure 5. Swelling ratio of poly(HEMA) and poly(HEMA-co-HCMA)

hydrogels in distilled water at 378C.

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hydrogels was freezing and thus hydrogels showed rigidproperty with a high storage modulus. However, the storagemodule was decreased by several orders of magnitude around08C because the freezing water melts. After that phase, thestorage module deceased slightly with increase in temperature.Storage modulus of poly(HEMA-co-HCMA) hydrogel was slightlyhigher than that of poly(HEMA) hydrogel over whole temperaturerange. The higher modulus was partly attributed to thecomonomer HCMA bearing rigid cyclohexyl group as expected.Further, the improvement in mechanical properties might beattributed to HCMA hydrophobic chain conglomerated inthree-dimensional networks. Finally, another non-negligiblereason was the difference of equilibrium water content betweenhomopolymeric hydrogel and copolymeric hydrogel. The degreeof swelling was intimately related to the material strength of ahydrogel. As polymer swelled in a plasticizing solvent, the glasstransition temperature of the mixture decreased and the materialwas weakened. Increase in the degree of swelling would lead to areduction in the mechanical strength. Therefore, the storagemodulus of homopolymeric hydrogel with high degree ofswelling was lower than that of copolymeric hydrogel.

Figure 4. Plot of storage modulus versus temperature.

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Swelling characteristic

Swelling behavior was a significant property of hydrogelsbecause it reflected materials’ microstructure and determinedtheir application. Major factors that influenced the degree ofswelling included the properties of the polymer (charge,concentration and pKa of the ionizable group, degree ofionization, crosslink density and hydrophilicity, or hydrophobi-city) and the properties of the swelling medium (pH, ionicstrength, the counter ion, and its valency). Design of drug carrierswas largely dependent on the swelling kinetics of the carrierswhich affected the controlled release property.A series of hydrogels with various monomer compositions

were prepared via photopolymerization technology and theirswelling behaviors were investigated in distilled water at378C. Figure 5 shows the swelling kinetics curves of differenthydrogel samples. Swelling capabilities of all hydrogel samplesincreased with prolonged time. Constant equilibrium swelling ofhydrogels with different compositions reached at different time:hydrogel with higher HCMA content took longer time to reachequilibrium and homopolymeric hydrogel obviously took shortertime to reach equilibrium. The equilibrium water content (EWC)of poly(HEMA) hydrogel was larger than that of copolymerichydrogels and EWC of poly(HEMA-co-HCMA) hydrogelsdecreased slightly from S2 to S4, while S5 exhibited a littlehigher EWC. The effect of hydrophobic comonomer on theswelling behavior of hydrogels was investigated by manyresearchers.[29–32] The direct reason for slow swelling behaviorsof copolymeric hydrogels was the addition of comonomer HCMA,which led to change in polymer secondary structure. HCMAbearing hydrophobic cyclohexyl group was less soluble in water,which would result in heterogeneity in the network andinteraction among hydrophobic chains. It was reasonable thatthe increase in the content of hydrophobic comonomer led todecrease in the hydrophilicity of hydrogels, and thus the EWCreduced from S2 to S4.The higher EWC of S5 could be explainedby the copolymeric hydrogel microstructure. High concentrationcomonomer led to heterogeneity in the precursor solution duringpolymerization that caused the formation of larger pores in thehydrogel microstructure. In swelling test, water entered thesepores and led to higher EWC.

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Figure 8. Average diameter of hydrogel pores.

Figure 6. Cumulative release of AO8 from different hydrogels.

PHOTOPOLYMERIZATION OF ALICYCLIC METHACRYLATE

Controlled release of AO8 as model drug

In some cases, prolonged and sustained controlled drug releasewas desirable. Controlled release property of hydrogels could beeffectively altered by changing the monomer ratio. Figure 6shows the cumulative release profiles of AO8 as modelcompound [28] from poly(HEMA) and poly(HEMA-co-HCMA)hydrogels with various monomer ratio in distilled water at378C. Controlled release property of poly (HEMA) hydrogel wasobviously different from that of poly(HEMA-co-HCMA) hydrogels,as illustrated in Fig. 6. Within the first 200 hr, over 80% AO8 wasreleased from poly(HEMA) hydrogel. However, due to theaddition of comonomer HCMA in hydrogel composition, theAO8 release was dramatically retarded and the release time wasalso greatly prolonged. The higher the content of the HCMA, theslower was the release rate except for S5. Increase in the HCMAratio in hydrogel precursor solution could reduce the release rateand prolong release time. The result of S5 was in accordance withits swelling characteristic and EWC results. High concentrationcomonomer led to the formation of a number of pores whichreserved amounts of AO8. When the disk samples were immersedin distilled water, AO8 reserved in pores released rapidly.

Figure 7. Scanning electron microphotographs of p

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Surface morphology of hydrogels

Scanning electron microscopy (SEM) as a commonly usedmethod directly characterized the morphology of hydro-gels.[33–35] SEM micrographs of freeze-dried poly(HEMA) andpoly(HEMA-co-HCMA) hydrogel samples with different feedcompositions are presented in Fig. 7. The surface morphologiesof the copolymeric hydrogels were very different from that ofhomopolymeric hydrogel. Copolymeric hydrogels displayedporosity, while poly(HEMA) hydrogel had a smooth surface.The calculated average diameter of the pores on hydrogelsurfaces ranged from 2 to 10mm, as illustrated in Fig. 8. It wasobserved from the SEM images that the higher the ratio ofHCMA was, the larger the pores were. The microporoussurface structure of the copolymeric hydrogels was undoubtedlycaused by the addition of hydrophobic comonomer HCMAand the monomer ratio influenced the pore size. Hydrophobicmonomer in precursor solution led to the micro-phase separa-tion during the photopolymerization. Heterogeneity of theresultant hydrogels caused the opacity of the copolymerichydrogel and led to the formation of pores on the hydrogelsurface.

oly(HEMA) and poly(HEMA-co-HCMA) hydrogels.

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CONCLUSIONS

Alicyclic hydroxy methacrylate monomer, o-hydroxycyclohexylmethacrylate (HCMA), was synthesized from cyclohexene oxideand methacrylic acid. FT-IR and 1H-NMR spectroscopies con-firmed its chemical structure. Real-time near infrared spec-troscopy was utilized to investigate its photopolymerizationactivity and the results indicated that HCMA polymerized fasterthan hydroxyethyl methacrylate (HEMA), but the final doubleconversion of HCMAwas lower than that of HEMA. Increase in thephotoinitiator concentration could improve final double bondconversion. Hydrogels based on HEMA and HCMAwere preparedby using the photopolymerization technique. Poly(HEMA-co-HCMA) hydrogel had a higher storage modulus than that ofpoly(HEMA) hydrogel. The copolymeric hydrogels showeddifferent swelling features and controlled release behaviors fromhomopolymeric hydrogel. Increase in HCMA ratio in hydrogelcomposition could reduce the swelling rate and prolong the drugrelease time. SEM photographs demonstrated that copolymerichydrogels had a pore structure on the surface and HCMA ratioinfluenced pore diameter, whereas homopolymeric hydrogelshowed smooth surface. The addition of alicyclic hydroxymethacrylate monomer HCMA might be a facile way of adjustinghydrogel structure and properties.

Acknowledgements

The authors thank the Program for Changjiang Scholars andInnovative Research Team in University.

REFERENCES

[1] J. L. Drury, D. J. Mooney, Biomaterials 2003, 24, 4337–4351.[2] K. T. Nguyen, J. L. West, Biomaterials 2003, 23, 4307–4314.[3] B. Balakrishnan, A. Jayakrishnan, Biomaterials 2005, 26, 3941–3951.

www.interscience.wiley.com/journal/pat Copyright � 2008

[4] Y. J. Zhang, S. P. Wang, M. Eghtedari, M. Motamedi, N. A. Kotov, Adv.Funct. Mater. 2005, 15, 725–731.

[5] Q. Yong, P. Kinam, Adv. Drug. Deliver. Rev. 2001, 53, 321–339.[6] E. Eljarrat-Binstock, A. Bentolila, N. Kumar, H. Harel, A. J. Domb, Polym.

Adv. Technol. 2007, 18, 528–532.[7] T. Y. Liu, S. H. Hu, T. Y. Liu, D. M. Liu, S. Y. Chen, Langmuir 2006, 22,

5974–5978.[8] X. Z. Zhang, P. J. Lewis, C. C. Chu, Biomaterials 2005, 26, 3299–3309.[9] J. A. Hubbell, J. Controlled. Release 1996, 39, 305–313.[10] C. Y. Cheung, K. S. Anseth, Bioconjugate Chem. 2006, 17, 1036–1042.[11] A. Barnes, P. H. Corkhill, B. J. Tighe, Polymer 1988, 29, 2191–2202.[12] C. B. St. Pourcain, A. W. P. Jarvie, B. J. Tighe, J. Mater. Chem 1998, 8,

21–24.[13] P. H. Corkhill, B. J. Tighe, Polymer 1990, 31, 1526–1537.[14] E. C. Muniz, G. Geuskens, Macromolecules 2001, 34, 4480–4484.[15] E. Marsano, E. Bianchi, S. Vicini, et al. Polymer 2005, 46, 1595–1600.[16] S. P. Zhao, D. Ma, L. M. Zhang, Macromol. Biosci. 2006, 6, 445–451.[17] Z. S. Akdemir, N. Kayaman-Apohan, Polym. Adv. Technol. 2007, 18,

932–939.[18] S. F. Li, X. L. Liu, Polym. Adv. Technol. 2008, 19, 317–376.[19] D. Myung, D. Waters, M. Wiseman, P. E. Duhamel, J. Noolandi, C. N. Ta,

C. W. Frank, Polym. Adv. Technol. 2008, 19, 647–657.[20] J. P. Gong, Y. Katsuyama, T. Kurokawa, Y. Osada, Adv. Mater. 2003, 15,

1155–1158.[21] Y. H. Na, Y. Tanaka, Y. Kawauchi, H. Furukawa, T. Sumiyoshi, J. P. Gong,

Y. Osada, Macromolecules 2006, 39, 4641–4644.[22] J. H. Wu, J. M. Lin, M. Zhou, C. R. Wei, Macromol. Rapid. Commun.

2000, 21, 1032–1034.[23] Y. Q. Xiang, Z. Q. Peng, D. J. Chen, Eur. Polym. J. 2006, 42, 2125–2132.[24] L. Lecamp, B. Youssef, C. Bunel, P. Lebaudy, Polymer 1997, 88,

6089–6096.[25] T. Scherzer, U. Decker, Vib. Spectrosc 1999, 19, 385–398.[26] T. Scherzer, U. Decker, Radiat. Phys. Chem. 1999, 55, 615–619.[27] C. G. Williams, A. N. Malik, T. K. Kim, P. N. Manson, J. H. Elisseeff,

Biomaterials 2005, 26, 1211–1218.[28] S. X. Liu, K. S. Anseth, J. Control. Release 1999, 57, 291–300.[29] W. F. Lee, Y. C. Yeh, Eur. Polym. J. 2005, 41, 2488–2495.[30] W. Xue, I. W. Hamley, Polymer 2002, 43, 3069–3077.[31] T. Caykara, G. Birlik, Macromol. Mater. Eng. 2005, 290, 869–874.[32] T. Caykara, G. Birlik, J. Appl .Poly. Sci. 2006, 101, 4159–4166.[33] S. H. Kim, C. C. Chu, J. Biomed. Mater. Res. 2000, 53B, 258–266.[34] L. Ferreira, M. M. Figueiredo, M. H. Gil, M. A. Ramos, J. Biomed. Mater.

Res. 2006, 77B, 55–64.[35] X. Z. Zhang, Y. Y. Yang, T. S. Chung, Langmuir 2002, 18, 2538–2542.

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