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PLA blend fibers
Materials Letters 60 (2006) 757 – 760 www.elsevier.com/locate/matlet
Preparation of porous ultrafine PGA fibers via selective dissolution of electrospun PGA / PLA blend fibers Young You a , Ji Ho Youk b,⁎, Sung Won Lee a , Byung-Moo Min c , Seung Jin Lee d , Won Ho Park a,⁎ a
b
Department of Textile Engineering, Chungnam National University, Daejeon 305-764, South Korea Department of Advanced Fiber Engineering, Division of Nano-Systems, Inha University, Incheon 402-751, South Korea c Department of Oral Biochemistry, College of Dentistry, Seoul National University, Seoul 110-749, South Korea d College of Pharmacy, Ewha Wowans University, Seoul 120-750, South Korea Received 1 February 2005; accepted 3 October 2005 Available online 24 October 2005
Abstract In order to prepare porous ultrafine poly(glycolic acid) (PGA) fibers, ultrafine PGA/poly(L-lactic acid) (PLA) blend fibers were electrospun and then the PLA was removed via a selective dissolution technique with chloroform. PGA and PLA are immiscible and that a co-continuous phase morphology was developed during the electrospinning process. After extraction of the PLA, the resulting PGA fibers had threedimensionally interconnected pores with a circular shape and the pore size distribution was very narrow. © 2005 Elsevier B.V. All rights reserved. Keywords: Poly(glycolic acid); Poly(L-lactic acid); Electrospinning; Selective dissolution; Porous ultrafine fibers
1. Introduction Electrospinning is a unique technique for the preparation of ultrafine polymer fibers with diameters in submicrometers. Since electrospun ultrafine fiber mats have high specific surface area and high porosity, they can be applied for membranes, wound dressings, scaffolds, sensors, etc. [1–5]. Recently, electrospinning of biodegradable and biocompatible poly (glycolic acid) (PGA), poly(L-lactic acid) (PLA), and their random copolymers have attracted a great deal of attention particularly for drug delivery, surgical implantation, enzyme immobilization, tissue regeneration, prevention of post-operative induced adhesions, etc. [6–13]. In our previous study [14], porous ultrafine polyetherimide (PEI) fibers were prepared via selective thermal degradation of electrospun PEI/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) blend fibers. They were partially miscible and that the phase separation occurred during the electrospinning process. After the selective thermal degradation of PHBV in the ultrafine ⁎ Corresponding authors. Tel.: +82 42 821 6613; fax: +82 42 823 3736. E-mail addresses: [email protected] (J.H. Youk), [email protected] (W.H. Park). 0167-577X/$ - see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.matlet.2005.10.007
PEI/PHBV blend fibers at 210 °C, the remaining PEI fibers had highly porous surfaces. Porous ultrafine fibers can be also prepared via electrospinning of immiscible polymer blends, followed by selective thermal or photo degradation of one component. If two polymers are immiscible, a phase-separated composite structure can be formed during the electrospinning process. It was suggested that these porous ultrafine fibers have potential applications in nanofiltration and functional nanotubes [15–17]. In this study, biodegradable ultrafine PGA fibers with a highly porous structure were prepared via a selective dissolution technique. PGA / PLA blend solutions in 1,1,1,3,3,3-hexafluoro2-propanol (HFIP) were electrospun and most of PLA was selectively extracted with chloroform. It is expected that ultrafine PGA fibers will show a different biodegradability according to their porosity. 2. Experimental PGA (Mw = 14,000 − 20,000) and PLA (Mw = 450,000) were purchased from Purac Co. and Boehringer Ingelheim, respectively. HFIP and chloroform were purchased from Aldrich Co. and used as received. In order to prepare PGA /
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Y. You et al. / Materials Letters 60 (2006) 757–760
Fig. 1. SEM images of ultrafine PGA / PLA fibers: (a) PGA, (b) PGA / PLA (90 / 10), (c) PGA / PLA (70 / 30), (d) PGA/ PLA (50/ 50), (e) PGA / PLA (30 / 70), and (f) PLA.
PLA blend solutions, 8 wt.% PGA and 5 wt.% PLA solutions in HFIP, respectively, were first prepared and then mixed at predetermined ratios (PGA / PLA = 90 / 10, 70 / 30, 50 / 50, 30 / 70, w / w). The electrospinning setup used in this study consisted of a syringe and needle (ID = 0.495 mm), an aluminum collecting plate, and a high voltage supply (Chungpa EMT) [18–20]. The PGA / PLA solutions were electrospun at a positive voltage of 17 kV and a working distance of 7 cm (the distance between the needle tip and the collecting plate). The mass flow rate of the PGA / PLA solutions was 4 mL/h. The electrospinning processes were carried out at 25 °C. The morphologies and pore structures of the electrospun PGA / PLA fibers and the residual PGA fibers were observed by a field emission scanning electron microscope (FE-SEM, JSM-6335F, JEOL). Prior to the observation, SEM specimens were coated with platinum by ion beam sputtering for a few seconds. Differential scanning calorimetry (DSC) measurements were conducted with a Perkin-Elmer DSC-7 under nitrogen atmosphere. About 10 mg of sample were sealed in an aluminum pan for the measurement. In order to remove thermal history, the samples
Fig. 2. DSC thermograms of ultrafine PGA/ PLA blend fibers: (a) PGA, (b) PGA / PLA (70 / 30), (c) PGA / PLA (50 / 50), (d) PGA / PLA (30 / 70), and (e) PLA.
Y. You et al. / Materials Letters 60 (2006) 757–760 Table 1 Weight percentages of the remaining fibers after extraction of the PLA Fibers
Remaining fibers (%)
PGA / PLA (90 / 10) PGA / PLA (70 / 30) PGA / PLA (50 / 50) PGA / PLA (30 / 70)
97.3 74.2 56.5 38.6
were heated to 250 °C, held at this temperature for 1 min, and then quenched to 0 °C. The samples were reheated to 250 °C at a heating rate of 20 °C/min. 3. Results and discussion The cross-sectional morphology of electrospun fibers is strongly affected by the electrospinning parameters, such as solution concentration and volatility of solvent. Fig. 1 shows the SEM images of ultrafine PGA, PGA / PLA blend, and PLA fibers. All the ultrafine fibers were round-shaped and their average diameters were ranged from 200 to 500 nm. The miscibility between polymer blend pairs can be determined by measuring their thermal properties [21]. When blend pairs are miscible at the molecular level, a single, composition-dependent Tg between Tgs of blend components is observed. If one of the blend components is crystalline, its crystallization is hindered by a miscible pair, and so its Tm and crystallinity are significantly decreased with increasing the content of the other component. Fig. 2 shows the DSC thermograms of the ultrafine PGA, PGA / PLA blend, and PLA fibers. Both PGA and PLA are crystalline polymers and PGA has higher crystallinity than PLA. For the ultrafine PGA / PLA fibers, any transition peaks were not significantly shifted for all blend compositions. This result clearly indicates that PGA and PLA are immiscible and the ultrafine PGA / PLA fibers have a phase-separated structure. Porous fibers can be prepared by selective dissolution, thermal degradation, or photo-degradation of one polymer component in phaseseparated fibers. Bognitzki et al. [22] electrospun PLA/poly(vinyl pyrrolidone) (PVP) blend fibers and prepared porous fibers via selective dissolution of one component. In this study, similarly, PLA was removed from the ultrafine PGA / PLA blend fibers via a selective dissolution technique. PGA is a highly crystalline polymer and that it is insoluble in many common organic solvents. In contrast, PLA can be
Fig. 3. DSC thermograms of ultrafine PGA / PLA (50 / 50) fibers (a) before and (b) after extraction of the PLA.
759
readily dissolved in common solvents such as chloroform. The weight percentages of the remaining PGA fibers after selective dissolution of the PLA with chloroform are listed in Table 1, which were determined by weighing the dried fibers before and after dissolution of the PLA for 2 h. Most of the PLA was dissolved and extracted by chloroform. Fig. 3 shows the DSC thermograms of PGA / PLA (50 / 50) blend fibers before and after dissolution of the PLA. A small melting peak for PLA was observed due to a small amount of residual PLA (see Table 1). Fig. 4 shows the SEM images of the porous ultrafine PGA fibers. Some of the remaining PGA fibers adhered together. The porous ultrafine PGA fibers had pores with a circular shape and their size distributions were very narrow. The average pore sizes were not significantly increased, however, the pore densities were increased according to the blend ratio of PLA. It is noticeable that the porous ultrafine PGA fibers obtained from ultrafine PGA / PLA (30 / 70) fibers maintained a continuous fiber structure after extraction of the PLA, although they had a somewhat flat
Fig. 4. SEM images of the remaining PGA fibers after extraction of the PLA: (a) PGA / PLA (70 / 30), (b) PGA / PLA (50 / 50), and (c) PGA / PLA (30 / 70).
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Y. You et al. / Materials Letters 60 (2006) 757–760
shape. This indicates that ultrafine PGA / PLA blend fibers have a cocontinuous phase morphology and that the pores in the remaining PGA fibers are three-dimensionally interconnected. The internal phase morphology of electrospun blend fibers is controlled by rapid phase separation and rapid solidification. When the homogeneous PGA / PLA solutions were electrospun, the solvent rapidly evaporated from the surface of the electrospun jet and that the phase separation of the homogeneous blend solutions started. However, the solidification of the electrospun jet also proceeded rapidly that the phase-separated regions were not able to coarsen strongly prior to the solidification. Bognitzki et al. [22] expected that a co-continuous phase morphology would be more favored than a matrix-dispersed phase morphology for electrospun PLA/PVP blend fibers because nucleation and growth decomposition needed more time to start than the initial growth of unstable concentration fluctuation. They reported that the electrospun PLA/PVP blend fibers had a cocontinuous phase morphology. Therefore, it is considered that the cocontinuous phase morphology in the PGA / PLA blend fibers were formed by spinodal phase separation.
4. Conclusions The ultrafine PGA / PLA blend fibers prepared by electrospinning of PGA / PLA solutions in HFIP were round-shaped and their average diameters were in the range of 200–500 nm. Most of the PLA was selectively removed by chloroform. The remaining PGA fibers had pores with a circular shape and their size distribution was very narrow. The ultrafine PGA / PLA blend fibers had a co-continuous phase morphology and that the pores in the resulting PGA fibers were three-dimensionally interconnected. Acknowledgments This work was supported by the Ministry of Science and Technology (Korea) and by the SRC/ERC program of MOST/ KOSEF (R11-2005-065).
References [1] P. Gibson, H. Schreuder-Gibson, D. Rivin, Colloids Surf., A Physicochem. Eng. Asp. 187–188 (2001) 469. [2] W. Li, C.T. Laurencin, E.J. Caterson, R.S. Tuan, F.K. Ko, J. Biomed. Mater. Res. 60 (2002) 613. [3] E.D. Boland, G.L. Bowlin, D.G. Simpson, G.E. Wnek, PMSE Preprints 85 (2001) 51. [4] S.A. Athreya, D.C. Martin, Sens. Actuators 72 (1999) 203. [5] X. Wang, C. Drew, S. Lee, K.J. Senecal, J. Kumar, L.A. Samuelson, PMSE Preprints 85 (2001) 617. [6] E.-R. Kenawy, G.L. Bowlin, K. Mansfield, J. Layman, D.G. Simpson, E. H. Sanders, G.E. Wnek, J. Control. Release 81 (2002) 57. [7] X. Zong, K. Kim, D. Fang, S. Ran, B.S. Hsiao, B. Chu, Polymer 43 (2002) 4403. [8] X. Zong, S. Ran, K.-S. Kim, D. Fang, B.S. Hsiao, B. Chu, Biomacromolecules 4 (2003) 416. [9] Y.K. Luu, K. Kim, B.S. Hsiao, B. Chu, M. Hadjiargyrou, J. Control. Release 89 (2003) 341. [10] J. Zeng, X. Xu, X. Chen, Q. Liang, X. Bian, L. Yang, X. Jing, J. Control. Release 92 (2003) 227. [11] X. Zong, S. Ran, D. Fang, B.S. Hsiao, B. Chu, Polymer 44 (2003) 4959. [12] J. Zeng, X. Chen, Q. Liang, X. Xu, X. Jing, Macromol. Biosci. 4 (2004) 1118. [13] K. Kim, Y.K. Luu, C. Chang, D. Fang, B.S. Hsiao, B. Chu, M. Hadjiargyrou, J. Control. Release 98 (2004) 47. [14] S.O. Han, W.K. Son, D. Cho, J.H. Youk, W.H. Park, Polym. Degrad. Stab. 86 (2004) 257. [15] M. Bognitzki, H. Hou, M. Ishaque, T. Frese, M. Hellwig, C. Schwarte, A. Schaper, J.H. Wendorff, A. Greiner, Adv. Mater. 12 (2000) 637. [16] R.A. Caruso, J.H. Schattka, A. Greiner, Adv. Mater. 13 (2001) 1577. [17] H. Hou, Z. Jun, A. Reuning, A. Schaper, J.H. Wendorff, A. Greiner, Macromolecules 35 (2002) 2429. [18] W.K. Son, J.H. Youk, T.S. Lee, W.H. Park, Polymer 45 (2004) 2959. [19] W.K. Son, J.H. Youk, T.S. Lee, W.H. Park, J. Polym. Sci., Polym. Phys. 42 (2004) 5. [20] W.K. Son, J.H. Youk, W.H. Park, Biomacromolecules 5 (2004) 197. [21] O. Olabisi, L.M. Robeson, M.T. Shaw, Polymer–Polymer Miscibility, Academic, New York, 1979. [22] M. Bognitzki, T. Frese, M. Steinhart, A. Greiner, J.H. Wendorff, Polym. Eng. Sci. 41 (2001) 982.
Preparation of porous ultrafine PGA fibers via selective dissolution of electrospun PGA / PLA blend fibers Young You a , Ji Ho Youk b,⁎, Sung Won Lee a , Byung-Moo Min c , Seung Jin Lee d , Won Ho Park a,⁎ a
b
Department of Textile Engineering, Chungnam National University, Daejeon 305-764, South Korea Department of Advanced Fiber Engineering, Division of Nano-Systems, Inha University, Incheon 402-751, South Korea c Department of Oral Biochemistry, College of Dentistry, Seoul National University, Seoul 110-749, South Korea d College of Pharmacy, Ewha Wowans University, Seoul 120-750, South Korea Received 1 February 2005; accepted 3 October 2005 Available online 24 October 2005
Abstract In order to prepare porous ultrafine poly(glycolic acid) (PGA) fibers, ultrafine PGA/poly(L-lactic acid) (PLA) blend fibers were electrospun and then the PLA was removed via a selective dissolution technique with chloroform. PGA and PLA are immiscible and that a co-continuous phase morphology was developed during the electrospinning process. After extraction of the PLA, the resulting PGA fibers had threedimensionally interconnected pores with a circular shape and the pore size distribution was very narrow. © 2005 Elsevier B.V. All rights reserved. Keywords: Poly(glycolic acid); Poly(L-lactic acid); Electrospinning; Selective dissolution; Porous ultrafine fibers
1. Introduction Electrospinning is a unique technique for the preparation of ultrafine polymer fibers with diameters in submicrometers. Since electrospun ultrafine fiber mats have high specific surface area and high porosity, they can be applied for membranes, wound dressings, scaffolds, sensors, etc. [1–5]. Recently, electrospinning of biodegradable and biocompatible poly (glycolic acid) (PGA), poly(L-lactic acid) (PLA), and their random copolymers have attracted a great deal of attention particularly for drug delivery, surgical implantation, enzyme immobilization, tissue regeneration, prevention of post-operative induced adhesions, etc. [6–13]. In our previous study [14], porous ultrafine polyetherimide (PEI) fibers were prepared via selective thermal degradation of electrospun PEI/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) blend fibers. They were partially miscible and that the phase separation occurred during the electrospinning process. After the selective thermal degradation of PHBV in the ultrafine ⁎ Corresponding authors. Tel.: +82 42 821 6613; fax: +82 42 823 3736. E-mail addresses: [email protected] (J.H. Youk), [email protected] (W.H. Park). 0167-577X/$ - see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.matlet.2005.10.007
PEI/PHBV blend fibers at 210 °C, the remaining PEI fibers had highly porous surfaces. Porous ultrafine fibers can be also prepared via electrospinning of immiscible polymer blends, followed by selective thermal or photo degradation of one component. If two polymers are immiscible, a phase-separated composite structure can be formed during the electrospinning process. It was suggested that these porous ultrafine fibers have potential applications in nanofiltration and functional nanotubes [15–17]. In this study, biodegradable ultrafine PGA fibers with a highly porous structure were prepared via a selective dissolution technique. PGA / PLA blend solutions in 1,1,1,3,3,3-hexafluoro2-propanol (HFIP) were electrospun and most of PLA was selectively extracted with chloroform. It is expected that ultrafine PGA fibers will show a different biodegradability according to their porosity. 2. Experimental PGA (Mw = 14,000 − 20,000) and PLA (Mw = 450,000) were purchased from Purac Co. and Boehringer Ingelheim, respectively. HFIP and chloroform were purchased from Aldrich Co. and used as received. In order to prepare PGA /
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Y. You et al. / Materials Letters 60 (2006) 757–760
Fig. 1. SEM images of ultrafine PGA / PLA fibers: (a) PGA, (b) PGA / PLA (90 / 10), (c) PGA / PLA (70 / 30), (d) PGA/ PLA (50/ 50), (e) PGA / PLA (30 / 70), and (f) PLA.
PLA blend solutions, 8 wt.% PGA and 5 wt.% PLA solutions in HFIP, respectively, were first prepared and then mixed at predetermined ratios (PGA / PLA = 90 / 10, 70 / 30, 50 / 50, 30 / 70, w / w). The electrospinning setup used in this study consisted of a syringe and needle (ID = 0.495 mm), an aluminum collecting plate, and a high voltage supply (Chungpa EMT) [18–20]. The PGA / PLA solutions were electrospun at a positive voltage of 17 kV and a working distance of 7 cm (the distance between the needle tip and the collecting plate). The mass flow rate of the PGA / PLA solutions was 4 mL/h. The electrospinning processes were carried out at 25 °C. The morphologies and pore structures of the electrospun PGA / PLA fibers and the residual PGA fibers were observed by a field emission scanning electron microscope (FE-SEM, JSM-6335F, JEOL). Prior to the observation, SEM specimens were coated with platinum by ion beam sputtering for a few seconds. Differential scanning calorimetry (DSC) measurements were conducted with a Perkin-Elmer DSC-7 under nitrogen atmosphere. About 10 mg of sample were sealed in an aluminum pan for the measurement. In order to remove thermal history, the samples
Fig. 2. DSC thermograms of ultrafine PGA/ PLA blend fibers: (a) PGA, (b) PGA / PLA (70 / 30), (c) PGA / PLA (50 / 50), (d) PGA / PLA (30 / 70), and (e) PLA.
Y. You et al. / Materials Letters 60 (2006) 757–760 Table 1 Weight percentages of the remaining fibers after extraction of the PLA Fibers
Remaining fibers (%)
PGA / PLA (90 / 10) PGA / PLA (70 / 30) PGA / PLA (50 / 50) PGA / PLA (30 / 70)
97.3 74.2 56.5 38.6
were heated to 250 °C, held at this temperature for 1 min, and then quenched to 0 °C. The samples were reheated to 250 °C at a heating rate of 20 °C/min. 3. Results and discussion The cross-sectional morphology of electrospun fibers is strongly affected by the electrospinning parameters, such as solution concentration and volatility of solvent. Fig. 1 shows the SEM images of ultrafine PGA, PGA / PLA blend, and PLA fibers. All the ultrafine fibers were round-shaped and their average diameters were ranged from 200 to 500 nm. The miscibility between polymer blend pairs can be determined by measuring their thermal properties [21]. When blend pairs are miscible at the molecular level, a single, composition-dependent Tg between Tgs of blend components is observed. If one of the blend components is crystalline, its crystallization is hindered by a miscible pair, and so its Tm and crystallinity are significantly decreased with increasing the content of the other component. Fig. 2 shows the DSC thermograms of the ultrafine PGA, PGA / PLA blend, and PLA fibers. Both PGA and PLA are crystalline polymers and PGA has higher crystallinity than PLA. For the ultrafine PGA / PLA fibers, any transition peaks were not significantly shifted for all blend compositions. This result clearly indicates that PGA and PLA are immiscible and the ultrafine PGA / PLA fibers have a phase-separated structure. Porous fibers can be prepared by selective dissolution, thermal degradation, or photo-degradation of one polymer component in phaseseparated fibers. Bognitzki et al. [22] electrospun PLA/poly(vinyl pyrrolidone) (PVP) blend fibers and prepared porous fibers via selective dissolution of one component. In this study, similarly, PLA was removed from the ultrafine PGA / PLA blend fibers via a selective dissolution technique. PGA is a highly crystalline polymer and that it is insoluble in many common organic solvents. In contrast, PLA can be
Fig. 3. DSC thermograms of ultrafine PGA / PLA (50 / 50) fibers (a) before and (b) after extraction of the PLA.
759
readily dissolved in common solvents such as chloroform. The weight percentages of the remaining PGA fibers after selective dissolution of the PLA with chloroform are listed in Table 1, which were determined by weighing the dried fibers before and after dissolution of the PLA for 2 h. Most of the PLA was dissolved and extracted by chloroform. Fig. 3 shows the DSC thermograms of PGA / PLA (50 / 50) blend fibers before and after dissolution of the PLA. A small melting peak for PLA was observed due to a small amount of residual PLA (see Table 1). Fig. 4 shows the SEM images of the porous ultrafine PGA fibers. Some of the remaining PGA fibers adhered together. The porous ultrafine PGA fibers had pores with a circular shape and their size distributions were very narrow. The average pore sizes were not significantly increased, however, the pore densities were increased according to the blend ratio of PLA. It is noticeable that the porous ultrafine PGA fibers obtained from ultrafine PGA / PLA (30 / 70) fibers maintained a continuous fiber structure after extraction of the PLA, although they had a somewhat flat
Fig. 4. SEM images of the remaining PGA fibers after extraction of the PLA: (a) PGA / PLA (70 / 30), (b) PGA / PLA (50 / 50), and (c) PGA / PLA (30 / 70).
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Y. You et al. / Materials Letters 60 (2006) 757–760
shape. This indicates that ultrafine PGA / PLA blend fibers have a cocontinuous phase morphology and that the pores in the remaining PGA fibers are three-dimensionally interconnected. The internal phase morphology of electrospun blend fibers is controlled by rapid phase separation and rapid solidification. When the homogeneous PGA / PLA solutions were electrospun, the solvent rapidly evaporated from the surface of the electrospun jet and that the phase separation of the homogeneous blend solutions started. However, the solidification of the electrospun jet also proceeded rapidly that the phase-separated regions were not able to coarsen strongly prior to the solidification. Bognitzki et al. [22] expected that a co-continuous phase morphology would be more favored than a matrix-dispersed phase morphology for electrospun PLA/PVP blend fibers because nucleation and growth decomposition needed more time to start than the initial growth of unstable concentration fluctuation. They reported that the electrospun PLA/PVP blend fibers had a cocontinuous phase morphology. Therefore, it is considered that the cocontinuous phase morphology in the PGA / PLA blend fibers were formed by spinodal phase separation.
4. Conclusions The ultrafine PGA / PLA blend fibers prepared by electrospinning of PGA / PLA solutions in HFIP were round-shaped and their average diameters were in the range of 200–500 nm. Most of the PLA was selectively removed by chloroform. The remaining PGA fibers had pores with a circular shape and their size distribution was very narrow. The ultrafine PGA / PLA blend fibers had a co-continuous phase morphology and that the pores in the resulting PGA fibers were three-dimensionally interconnected. Acknowledgments This work was supported by the Ministry of Science and Technology (Korea) and by the SRC/ERC program of MOST/ KOSEF (R11-2005-065).
References [1] P. Gibson, H. Schreuder-Gibson, D. Rivin, Colloids Surf., A Physicochem. Eng. Asp. 187–188 (2001) 469. [2] W. Li, C.T. Laurencin, E.J. Caterson, R.S. Tuan, F.K. Ko, J. Biomed. Mater. Res. 60 (2002) 613. [3] E.D. Boland, G.L. Bowlin, D.G. Simpson, G.E. Wnek, PMSE Preprints 85 (2001) 51. [4] S.A. Athreya, D.C. Martin, Sens. Actuators 72 (1999) 203. [5] X. Wang, C. Drew, S. Lee, K.J. Senecal, J. Kumar, L.A. Samuelson, PMSE Preprints 85 (2001) 617. [6] E.-R. Kenawy, G.L. Bowlin, K. Mansfield, J. Layman, D.G. Simpson, E. H. Sanders, G.E. Wnek, J. Control. Release 81 (2002) 57. [7] X. Zong, K. Kim, D. Fang, S. Ran, B.S. Hsiao, B. Chu, Polymer 43 (2002) 4403. [8] X. Zong, S. Ran, K.-S. Kim, D. Fang, B.S. Hsiao, B. Chu, Biomacromolecules 4 (2003) 416. [9] Y.K. Luu, K. Kim, B.S. Hsiao, B. Chu, M. Hadjiargyrou, J. Control. Release 89 (2003) 341. [10] J. Zeng, X. Xu, X. Chen, Q. Liang, X. Bian, L. Yang, X. Jing, J. Control. Release 92 (2003) 227. [11] X. Zong, S. Ran, D. Fang, B.S. Hsiao, B. Chu, Polymer 44 (2003) 4959. [12] J. Zeng, X. Chen, Q. Liang, X. Xu, X. Jing, Macromol. Biosci. 4 (2004) 1118. [13] K. Kim, Y.K. Luu, C. Chang, D. Fang, B.S. Hsiao, B. Chu, M. Hadjiargyrou, J. Control. Release 98 (2004) 47. [14] S.O. Han, W.K. Son, D. Cho, J.H. Youk, W.H. Park, Polym. Degrad. Stab. 86 (2004) 257. [15] M. Bognitzki, H. Hou, M. Ishaque, T. Frese, M. Hellwig, C. Schwarte, A. Schaper, J.H. Wendorff, A. Greiner, Adv. Mater. 12 (2000) 637. [16] R.A. Caruso, J.H. Schattka, A. Greiner, Adv. Mater. 13 (2001) 1577. [17] H. Hou, Z. Jun, A. Reuning, A. Schaper, J.H. Wendorff, A. Greiner, Macromolecules 35 (2002) 2429. [18] W.K. Son, J.H. Youk, T.S. Lee, W.H. Park, Polymer 45 (2004) 2959. [19] W.K. Son, J.H. Youk, T.S. Lee, W.H. Park, J. Polym. Sci., Polym. Phys. 42 (2004) 5. [20] W.K. Son, J.H. Youk, W.H. Park, Biomacromolecules 5 (2004) 197. [21] O. Olabisi, L.M. Robeson, M.T. Shaw, Polymer–Polymer Miscibility, Academic, New York, 1979. [22] M. Bognitzki, T. Frese, M. Steinhart, A. Greiner, J.H. Wendorff, Polym. Eng. Sci. 41 (2001) 982.