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Synthesis of Macroporous Thermosensitive Hydrogels: A Novel Method of Controlling Pore Size Qian Zhao, Jianzhong Sun,* Qincai Ling, and Qiyun Zhou State Key Laboratory of Chemical Engineering, Department of Chemical and Biochemical Engineering, Zhejiang UniVersity, Hangzhou 310027, China ReceiVed NoVember 25, 2008. ReVised Manuscript ReceiVed January 7, 2009 Macroporous thermosensitive poly(N-isopropylacrylamide) hydrogels were synthesized in the presence of dodecyl dimethyl benzyl ammonium bromide (DDBAB). Poly(vinyl alcohol) (PVA) was involved to control the pore size of the hydrogels. The morphology of the resulting hydrogels was studied by both an optical microscope and a scanning electron microscope. Moreover, the pore size and its distribution were examined by mercury intrusion porosimetry. The results indicated that size of the pores decreased with the increase of the amount of PVA added. The mechanism was explained after dynamic light scattering measurement of the size of hydrophobic initiator DDBAPS aggregates that were formed in situ in PVA aqueous solutions of various concentrations as the product of the reaction between DDBAB and the water soluble initiator ammonium persulfate. Swelling ratio and deswelling/reswelling kinetics of the hydrogels were also measured to investigate the response properties of the hydrogels. It would be a promising method of pore size control for synthesizing hydrogels of other vinyl monomers that could be initiated by persulfates.
Introduction Hydrogels are three-dimensional polymeric networks that are able to absorb and retain large amounts of water. Because of their water-absorbing capability, hydrogels have attracted significant attention in both fundamental aspects and application areas, such as controlled drug delivery,1 tissue engineering,2 actuators,3 on-off switches,4 separation operations,5 column packing materials for chromatography,6 immobilization of enzyme,7 and so on. During the past decade, many researchers have been committing themselves to fabricate porous hydrogels, because porous hydrogels have much larger specific surface areas and a much more rapid swelling-deswelling rate than nonporous hydrogels. Moreover, macroporous hydrogels are promising scaffolds for tissue engineering applications, while nonporous hydrogels are hard to use.8,9 Generally speaking, macroporous hydrogels can be achieved by the following methods: 1. The solvents (mixed solvents such as water/acetone10 or water/tetrahydrofuran,11 aqueous NaCl solution,12 and so on) that are used for preparing hydrogels are good solvents for the monomers but poor solvents for the formed polymers. 2. Polymerizations take place in the presence of inert substances (poly(ethylene glycol),13 silica particles,14 CO2,15 micronized * Corresponding author. E-mail:
[email protected]. (1) Qiu, Y.; Park, K. AdV. Drug DeliVer ReV. 2001, 53, 321–339. (2) Lee, K. Y.; Mooney, D. J. Chem. ReV. 2001, 101, 1869–1879. (3) Luo, Q. Z.; Mutlu, S.; Yogesh, B. Electrophoresis 2003, 24, 3694–3702. (4) Beebe, D. J.; Moore, J. S.; Bauer, J. M.; Yu, Q.; Liu, R. H.; Devadoss, C.; Jo, B. H. Nature 2000, 404, 588–590. (5) Castellanos, A.; DuPont, S.; Heim, A.; Matthews, G.; Stroot, P.; Moreno, W.; Toomey, R. Langmuir 2007, 23, 6391–6395. (6) Kanazawa, H.; Kashiwase, Y.; Yamamoto, K.; Matsushima, Y.; Kikuchi, A.; Sakurai, Y. Anal. Chem. 1997, 69, 823–830. (7) Ding, Z.; Chen, G.; Hoffman, A. S. J. Biomed. Mater. Res. 1998, 39, 498–505. (8) Woerly, S.; Petrov, P.; Sykova´, E.; Roitbak, T. Tissue Eng. 1999, 5, 467– 488. (9) Pradny, M.; Lesny, P.; Fiala, J.; Vacik, J.; Slouf, M.; Michalek, J.; Sykova, E. Collect. Czech. Chem. Commun. 2003, 68, 812–822. (10) Zhang, X. Z.; Zhuo, R. X.; Yang, Y. Y. Biomaterials 2002, 23, 1313– 1318. (11) Zhang, X. Z.; Yang, Y. Y.; Chung, T. S. Langmuir 2002, 18, 2538–2542. (12) Liu, Q.; Hedberg, E. L.; Liu, Z.; Bahulekar, R.; Meszlenyi, R. K.; Mikos, A. G. Biomaterials 2000, 21, 2163–2169. (13) Zhang, X. Z.; Zhuo, R. X. Eur. Polym. J. 2000, 36, 2301–2303.
sucrose16 or salts,17 oil-in-water emulsions,18 and so on), which are washed out from the hydrogel after polymerization. 3. Introducing freely mobile and grafted chains into the network of hydrogels can enlarge the pores of the polymeric matrixes.19-21 4. Hydrogels that are obtained at temperatures below the melting temperature of the solvent (so-called cryogels) are macroporous after melting the crystals of the solvents.22-26 5. Through a lyophilization-hydration procedure, nonporous hydrogels are likely to become porous sponges.27,28 Poly(N-isopropylacrylamide) (PNIPA) hydrogels are typical thermosensitive hydrogels exhibiting a reversible volume transition at a critical temperature (Tc) around 33 °C in aqueous media.29 The PNIPA hydrogels swell in water below the Tc and shrink as the temperature increases. The reversible temperatureresponsive property has been utilized in medicine, bioengineering, and many other fields.1-7 However, the response rate of traditional nonporous PNIPA hydrogels is slow because of the formation of a dense skin layer of the shrunken gel, which prevents the mass transport of water out of the shrinking gel.30 General (14) Serizawa, T.; Wakita, K.; Kaneko, T.; Akashi, M. J. Polym. Sci. Part A: Polym. Chem. 2002, 40, 4228–4235. (15) Behravesh, E.; Jo, S.; Zygourakis, K.; Mikos, A. G. Biomacromolecules 2002, 3, 374–381. (16) Oxley, H. R.; Corkhill, P. H.; Fitton, J. H.; Tighe, B. J. Biomaterials 1993, 14, 1064–1072. (17) Kima, J. H.; Lee, S. B.; Kim, S. J.; Lee, Y. M. Polymer 2002, 43, 7549– 7558. (18) Tokuyama, H.; Kanehara, A. Langmuir 2007, 23, 11246–11251. (19) Uchida, K.; Kaneko, Y.; Sakai, K.; Kikuchi, A.; Sakurai, Y.; Okano, T. Nature 1995, 374, 240–242. (20) Kaneko, Y.; Nakamura, S.; Sakai, K.; Aoyagi, T.; Kikuchi, A.; Sakurai, Y.; Okano, T. Macromolecules 1998, 31, 6099–6105. (21) Lynch, I.; Dawson, K. A. Macromol. Chem. Phys. 2003, 204, 443–450. (22) Lozinsky, V. I. Russ. Chem. ReV. 2002, 71, 489–511. (23) Zhang, X. Z.; Zhuo, R. X. Macromol. Chem. Phys. 1999, 200, 2602– 2605. (24) Xue, W.; Hamleya, I. W.; Huglinb, M. B. Polymer 2002, 43, 5181–5186. (25) Perez, P.; Plieva, F.; Gallardo, A.; Roman, J. S.; Aguilar, M. R.; Morfin, I.; Ehrburger-Dolle, F.; Bley, F.; Mikhalovsky, S.; Galaev, I. Yu.; Mattiasson, B. Biomacromolecules 2008, 9, 66–74. (26) Ozmena, M. M.; Okay, O. React. Funct. Polym. 2008, 68, 1467–1475. (27) Shapiro, L.; Cohen, S Biomaterials 1997, 583–590. (28) Kato, N.; Takahashi, F. Bull. Chem. Soc. Jpn. 1997, 70, 1289–1295. (29) Hirokawa, Y.; Tanaka, T. J. Chem. Phys. 1984, 81, 6379–6380. (30) Kaneko, Y.; Yoshida, R.; Sakai, K.; Sakurai, Y.; Okano, T. J. Membr. Sci. 1995, 101, 13–22.
10.1021/la8038939 CCC: $40.75 2009 American Chemical Society Published on Web 02/09/2009
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Figure 1. Reaction formula of DDBAB and APS.
strategies to improve the response rate of PNIPA hydrogels have been reported by Zhang recently.31 Fabricating macroporous hydrogels is one of the efficient methods for accelerating the response rate. The basic methods for preparing macroporous PNIPA hydrogels are similar to those of the other kinds of hydrogels, which have been mentioned above. Recently, a novel method for preparing macroporous PNIPA hydrogels was found in our laboratory.32 Unlike the other methods for forming macroporous hydrogels, the water soluble initiator ammonium persulfate (APS) was changed into the hydrophobic initiator dodecyl dimethyl benzyl ammonium persulfate (DDBAPS) in situ by adding a cation surfactant dodecyl dimethyl benzyl ammonium bromide (DDBAB). The reaction formula is shown in Figure 1. DDBAPS existed in the reaction medium in the form of aggregates with the size of several hundred nanometers.33 The aggregate size increased with time because of conglomeration, so polymerization was carried out in the frozen state in order to prevent DDBAPS from depositing out. Although the polymerization temperature is below the melting point of the solvents, the mechanism of pore forming is quite different from that of conventional cryogels.32,33 Cross-linking polymerization occurred around the DDBAPS aggregates; on the other hand, gelation could hardly take place in the areas that were a certain distance from the aggregates. As a result of this heterogeneous initiation system, hydrogels with interconnected macropores could be obtained. Subsequently, this kind of hydrogel was used as an enzyme carrier for enzymatic polymerization because of its macroporous and ultrarapid thermosensitive properties.34 Moreover, when water/1,4-dioxane mixed solvent was used for synthesizing this kind of hydrogel, the interconnected pores became unconnected.33 This method is promising as another basic method for preparing macroporous hydrogels that are initiated by persulfates, such as PNIPA, poly(acrylamide) (PAAm), poly(2-hydroxyethyl methacrylate) (PHEMA), their copolymers with other vinyl monomers hydrogels, and so on. However, some shortcomings of this method have been found. For example, when this kind of macroporous hydrogel is used as an enzyme carrier, the macropores are expected to be smaller so that the resulting hydrogels can obtain even larger specific surface areas.34 Another example is that, when authors utilized this kind of hydrogel to culture a type of colon bacillus, the bacilli were expected to be immobilized in the interconnected macropores of the hydrogels, but, unfortunately, the bacilli seemed to transfer in and out of the hydrogels freely during the swelling-deswelling process. Hydrogels with adjustable size of macropores are preferred so that different type of cells in various sizes would be immobilized in macropores with a more suitable size. (31) Zhang, X. Z.; Xu, X. D.; Cheng, S. X.; Zhuo, R. X. Soft Matter 2008, 4, 385–391. (32) Zhao, Q.; Sun, J. Z.; Zhou, Q. Y. J. Appl. Polym. Sci. 2007, 104, 4080– 4087. (33) Zhao, Q.; Sun, J. Z.; Ling, Q. C.; Zhou, Q. Y. J. Polym. Sci. Part A: Polym. Chem. 2008, 46, 6594–6603. (34) Zhao, Q.; Sun, J. Z.; Ren, H.; Zhou, Q. Y. J. Polym. Sci. Part A: Polym. Chem. 2008, 46, 2222–2232.
Figure 2. Schematic diagram of the formation of pores with adjustable size.
In this study, poly(vinyl alcohol) (PVA) is utilized to control the pore size of the PNIPA hydrogels when synthesizing the macroporous hydrogels in the presence of DDBAB, which is schematically shown in Figure 2. PVA is a well-known polymeric dispersant that is able to prevent the hydrophobic initiator DDBAPS from conglomerating together when the heterogeneous initiation system is formed. This conclusion was proven by dynamic light scattering (DLS) measurement of the size of DDBAPS aggregates in the absence or presence of PVA. The size of macropores can be adjusted with the size of DDBAPS aggregates, which is controlled by the amount of added PVA. The morphology of the resulting hydrogels was observed by both an optical microscope and a scanning electron microscope (SEM). The pore size was also examined by mercury intrusion porosimetry (MIP). Deswelling and reswelling kinetics showed that the macroporous hydrogels had a rapid response behavior, especially in reswelling, despite the presence or absence of PVA.
Experimental Section Materials. N-isopropylacrylamide (NIPA, 99%, Acros Organics, Fairlawn, NJ) was used after further recrystallization from n-hexane. N,N′-methylenebisacrylamide(BIS,g98%,FlukaChemika),N,N,N′,N′tetramethylethylenediamine (TEMED, 99%, Acros Organics), APS (g98%, Sinopharm Chemical Reagent Co. Ltd., China), PVA (degree of polymerization 2450 ( 50, alcoholysis degree 99%, Sinopharm Chemical Reagent Co.), and DDBAB (95%, Shanghai Jingwei Chemical Co., China) were used as received. Synthesis of PNIPA Hydrogels. The method for synthesizing macroporous PNIPA hydrogels was introduced in previous work.32 In this study, PVA was involved to control the size of DDBAPS aggregates obtained in situ and pores of the resulting hydrogels. Briefly, NIPA, BIS, DDBAB, and PVA (dissolved in hot water to get a 10 wt % aqueous solution in advance) were dissolved in deionized water in a glass vessel at room temperature. The solution was first cooled to 0 °C followed by adding APS and TEMED, and then polymerization was carried out at -8 °C for 12 h. After the reaction, the resulting gels were cut into disks (20 mm in diameter and 5 mm in thickness). The samples were immersed in excessive deionized water at ambient temperature for 72 h. Then the samples were refreshed by deionized water every several hours to remove the unreacted monomers and other impurities. Macroporous hydrogels prepared at various amounts of PVA were labeled as MG0, MG5, MG10, MG15, MG20, and MG30. Normal hydrogels (NG0 and
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Table 1. Feed Composition of the Hydrogels Gel samples NIPA (mg) BIS (mg) 4 wt % APS (µL) TEMED (µL) DDBAB (mg) water (mL) 10 wt % PVA (mL) weight of the xerogel (mg) conversion (%)a a
MG0
MG5
MG10
MG15
MG20
MG30
NG0
NG30
150 5 100 10 25 1.5 0 146.5 94.5
150 5 100 10 25 1.45 0.05 142.3 88.9
150 5 100 10 25 1.4 0.10 144.1 87.3
150 5 100 10 25 1.35 0.15 144.3 84.9
150 5 100 10 25 1.3 0.20 146.7 83.8
150 5 100 10 25 1.2 0.30 150.6 81.4
150 5 100 10 0 1.5 0 148.4 95.7
150 5 100 10 0 1.2 0.30 174.8 94.5
Weight percentage of the gel synthesized from the monomer, cross-linker, and PVA.
NG30) were prepared in the absence of DDBAB at room temperature. The feed compositions of the monomers and other reactants are summarized in Table 1. Morphology Observations of the Gels. For optical microscope observations, the wet gel samples were cut into disks of about 0.5 mm thickness and then observed directly without further treatment using an optical microscope (Nikon E600 POL, Japan) at room temperature. For SEM observations, the gel samples that reached equilibrium in deionized water were freeze-dried for 24 h. Specimens were coated with platinum by coating equipment (IB-5 ION coater, EIKO, Japan) for 2 min. The SEM morphology was studied using an SEM (Table Top Microscope TM-1000, Hitachi, Japan). MIP Examination. Measurement of MIP (AutoPore IV 9510, Micromeritics Instrument Corp., USA) was taken to examine porosity and pore size distribution of the freeze-dried macroporous hydrogels. All the samples were degassed before analysis at a vacuum pressure below 50 µmHg. High pressure runs (from 30 up to 60 000 psia) were performed with an equilibration time of 10 s and a maximum intrusion volume of 0.050 mL/g. Sizes of DDBAPS Aggregates. DDBAPS aggregates were formed in situ by the reaction of DDBAB and APS. The reaction conditions and the procedures of preparing DDBAPS were the same as those of the synthesis of MG hydrogels, except that the monomers NIPA and BIS were not involved. The concentrations of PVA solution were 0%, 0.67%, 1.33%, and 2% weight percent, corresponding with the synthesis of gels MG0, MG10, MG20, and MG30, respectively. The sizes of DDBAPS aggregates were measured by DLS measurement (Zetasizer3000HSA potential and laser nanometer particle size analyzer, Malvern, England) at 10 °C. In order to investigate the kinetics of size change of DDBAPS aggregates, the measurements were taken at various times of 2, 8, 14, and 20 min after APS was added. Measurement of Swelling Ratio of the Gels. The gel samples were measured gravimetrically after the excess water was wiped off with wet filter paper in the temperature range from 15 to 45 °C. Before the measurement, the gel samples were immersed in deionized water for at least 24 h at each given measurement temperature. The swelling ratio (SR) is defined as Ws/Wd, where Ws is the weight of water in the swollen sample at a given temperature and Wd is the weight of the sample in the dry state. Measurement of Deswelling-Reswelling Kinetics of the Gels. The equilibrated gel samples at a temperature of 15 °C were quickly transferred into hot deionized water of 45 °C, and then the deswelling kinetics were measured gravimetrically after removing excess water
from the surface of samples with filter paper. The reswelling kinetics of the shrunken samples that were immersed in hot water of 45 °C for at least 48 h were determined gravimetrically at 15 °C. The deswelling and reswelling kinetics were defined as temporal weight changes for the samples. The change of weight was converted to the normalized swelling degree, which indicated the volume changes of the samples between equilibrium swollen (100%) and equilibrium shrunken (0%) states. The swelling degree is defined as 100 × (Wt-W15)/(W45-W15), where Wt is the weight of sample at a given time, and W15 and W45 are the weights of samples that reached equilibrium at 15 °C and at 45 °C, respectively.
Results and Discussion Synthesis of the PNIPA Hydrogels. In appearance, gel NG0 was transparent and gel NG30 was translucent, and both were elastic hydrogels. All the MG gels (MG0, MG5, MG10, MG15, MG20, and MG30) were opaque and spongy hydrogels, the appearances of which were almost the same. For the MG gels, partial absorbed water could be driven out when a certain compressive stress was added directly to the gels. Figure 3 shows the procedure of the absorbed water being driven out of the sample and subsequently sucked up again. In this procedure, a piece of glass flat was used so that the compressive stress would be loaded uniformly. The whole procedure lasted for only 10 s. For the NG gels, the absorbed water could not be driven out even if the gels were compressed into breakage. The conversions are summarized in Table 1. For synthesis of NG gels (NG0 and NG30), the conversions were about 95%. For gel NG30, the weight of the dry sample was 174.8 mg while the whole weight of monomers (NIPA and BIS) was 155 mg, so it was certain that PVA chains were able to be immobilized in the gel matrix to form a semi-interpenetrating polymeric network (semi-IPN). For synthesis of MG gels, the conversions decreased with the increase of PVA added. The probable reason for the decrease of conversions was that a partial amount of PVA was washed out of the resulting gels though the interconnected pores. Morphology of the Hydrogels. Optical micrographs of swollen gel samples are shown in Figure 4. The matrixes of NG0 and NG30 that were are synthesized without DDBAB at room temperature are compact and smooth without pores. It indicates that the morphology of the gels would not be remarkably changed
Figure 3. The procedure of the absorbed water being driven out and subsequently sucked up again: (a) before compression; (b) when compression was being loaded, partial absorbed water was driven out; (c) when compression was removed, water could be sucked up again.
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Figure 4. Optical micrographs of the hydrogels at 100× magnification (the length bar is 50 µm).
when only PVA was added in the absence of DDBAB during the polymerization process. All of the MG gels are macroporous, but some remarkable differences can easily be found. For gels MG0 and MG5, the sizes of most pores of both gels are larger than 50 µm. However, the polymeric matrix of MG0 is smooth, while that of MG5 is uneven with a mass of small holes on it. For the MG gels except MG0 (MG5, MG10, MG15, MG20, and MG30, so-called PVA modified MG gels) which were synthesized in the presence of DDBAB and various amount of PVA, the morphologies of the polymeric matrixes are similar, but the size of macropores is diminished when the amount of added PVA increases. The size of pores of gel MG10 is about 50 µm, while that of MG30 is much smaller. Figure 5 shows the SEM micrographs of freeze-dried PNIPA hydrogels. For gels NG0 and NG30, although they were nonporous at their swollen state according to Figure 4, pores could be found after the freeze-drying process. It has been reported that the freeze-drying process could generate the porous structure of the gel and other polymers.35 Recently, some researchers studied the morphologies of conventional PNIPA hydrogels as well as PVA/PNIPA semi-IPN hydrogels after the freeze-drying process.36 The morphologies of NG gels observed by us were similar to those studied by the other researchers. The pore size of gel NG30 (semi-IPN) was much smaller than that of gel NG0 (conventional gel). It is thought that the hydrophilic PVA chains would destroy the compact gel matrix and act as water-releasing (35) Kato, N.; Sakai, Y.; Shibata, S. Macromolecules 2003, 36, 961–963. (36) Zhang, J. T.; Bhat, R.; Jandt, K. D. Acta Biomater. 2009, 5, 488–497.
Figure 5. SEM micrographs of the hydrogels at 1000× magnification (the length bar is 100 µm).
channels during the freeze-drying process, so that the pores would be very small. However, the exact reason is still uncertain. For gel MG0, although it is porous with pores of about 70 µm in diameter, the polymeric matrix is smooth. The polymeric matrixes of PVA-modified MG gels are much different from that of MG0. The matrixes of these gels are wrinkled and rough, and numerous small holes can clearly be found on the matrixes. The formation of the small holes was probably ascribed to the adding of PVA. The differences between these MG gels are visible. Pores become smaller and denser with the increase of the amount of added PVA, according with the optical micrographs. The pores of MG10 are around 50 µm in diameter, while, for MG15 and MG20, the pore diameters are distributed in the range of 20-50 µm. The density of the pores of MG30 is obviously larger than that of other MG gels, as the pore diameters are about 20 µm. Both the pore size and the trend of change observed using SEM are consistent with those observed using an optical microscope. Moreover, for the hydrogels that have interconnected porous structures at the swollen state, it is considered that the original pore structures are apt to be retained because the ice in the pores is likely to be removed earlier than the ice immobilized by the polymeric matrix during the freeze-drying procedure. On the basis of the morphology observations, it seems that adding various amount of PVA is an efficient method for adjusting the pore size of the hydrogels that were synthesized in the presence of DDBAB.
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Figure 6. Pore size distributions.
Figure 7. Volumetric sizes of DDBAPS aggregates at various times.
Table 2. Summary of the Results of MPI Gel samples MG0 median pore diameter (volume) (µm) total intrusion volume (mL/g) bulk density at 0.50 psia (g/mL) skeletal density (g/mL) porosity (%)
MG5
MG10 9.87
MG20 9.24
MG30
25.07
23.99
4.68
9.044
10.1595 7.1182 7.8183
6.2658
0.0942
0.0829
0.1109 0.1040
0.1179
0.6370
0.5236
0.5267 0.5567
0.4513
85.2098 84.1757 78.945 81.3161 73.8767
MIP Examination. Figure 6 shows the pore size distributions of the freeze-dried macroporous hydrogels. A summary of the results of MIP measurement is shown in Table 2. It can be seen that the median pore diameter diminished with the increase of the amount of added PVA. The pore diameter distributions become broader when a greater amount of PVA was involved. Pores about 1 µm can be found for MG10, MG20, and MG30, which were likely to be the small pores on the polymeric matrix corresponding to the SEM micrographs. It is normal that the pore diameter measured using MIP is smaller than the size of the pores observed by SEM,37 since the two techniques are of distinct measuring principles, size definitions, and sampled regions.38 However, similar trends are found for the effect of the amount of added PVA on the pore size of hydrogels. Sizes of DDBAPS Aggregates. According to the morphology observations of the hydrogels, the influence of adding PVA on the synthesis of MG gels in the presence of DDBAB is remarkable, while the effect of PVA on the morphology of NG gels is not significant. Therefore the size of DDBAPS aggregates, which were formed in situ in PVA aqueous solution of various concentrations as a product of the reaction of DDBAB and APS, was measured by DLS. The results are shown in Figure 7. All the distribution coefficients (ratios of volumetric sizes to numeric sizes) are less than 1.10. The measurements lasted 20 min for each sample in consideration of the fact that it took about 20 min for the reaction mixture to reach the frozen state from 0 °C. At the beginning, the sizes of DDBAPS aggregates are almost the same in 0%, 0.67%, and 1.33% PVA solutions, all of which are (37) Butler, R.; Hopkinson, I.; Cooper, A. I. J. Am. Chem. Soc. 2003, 125, 14473–14481. (38) Ferreira, L.; Figueiredo, M. M.; Gil, M. H.; Ramos, M. A. J. Biomed. Mater. Res. Part B: Appl. Biomater. 2006, 77, 55–64.
about 500 nm and are a little larger than that of DDBAPS aggregates formed in situ in 2% PVA solution. As time goes on, the size of aggregates in 0% PVA solution increases rapidly and reaches about 1150 nm after 20 min. For 0.67% and 1.33% PVA solutions, the rates of aggregate increase are much slower than that of aggregates formed in pure water. Twenty minutes later, the sizes of DDBAPS aggregates are about 850 nm in 0.67% PVA solution and about 700 nm in 1.33% PVA solution. When DDBAPS aggregates are formed in 2% PVA solution, the size of the aggregates increase from about 450 nm to about 480 nm, and this rate of size increase is very slow. In brief, the size of DDBAPS aggregates increases with time, and the rate of increase diminishes with the increase of the concentration of PVA solutions. The results indicate that DDBAPS aggregates would conglomerate as time goes on; moreover, PVA chains would prevent the aggregates from conglomerating. Relating with morphology of the macroporous hydrogels, the mechanism of controlling the pore size of hydrogels by adding various amount of PVA can be explained as follows: after adding APS to the prepolymerization solution to synthesize macroporous hydrogels in the presence of DDBAB, the size of the DDBAPS aggregates that were formed as the product of the reaction of DDBAB and APS increased remarkably because of conglomeration before the reaction mixture was frozen. When PVA was involved, the rate of conglomeration was slowed-down since small DDBAPS aggregates were dispersed by PVA chains. Furthermore, by using various amount of PVA, the size of DDBAPS aggregates could be controlled when the reaction mixture were finally frozen. Through freezing polymerization, larger DDBAPS aggregates would result in larger pores while smaller aggregates of the hydrophobic initiator would result in smaller pores. The reason for this matter was that the distances between larger DDBAPS aggregates were also larger than the distances between smaller aggregates when the total amount of DDBAPS was the same. A local region without DDBAPS aggregates would be a macropore after gelation reaction, and the area of a certain local region between larger DDBAPS aggregates that was larger than that between smaller aggregates would result in larger pores. Therefore the size of pores was adjustable using various amount of PVA to control the size of the DDBAPS aggregates. The schematic diagram is shown in Figure 2. Swelling Ratio. The equilibrium SR of the hydrogels are shown in Figure 8. The critical temperatures (Tc) of volume change are around 32 °C for all of the hydrogels. The SR of gel NG0 is low
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Figure 8. Equilibrium SR of the hydrogels.
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Figure 10. Reswelling kinetics of the gels at 15 °C from the equilibrium shrunken state at 45 °C.
and they enhance the shrinking rate.39 The gel NG30 reaches its equilibrium shrunken state in 4 min. For all of the MG gels, the deswelling kinetics are similar. The deswelling rates of MG gels are so fast that the gels reach their equilibrium shrunken state in just 1 min. The reswelling kinetics of gels after a temperature jump from 45 °C (above Tc) to 15 °C (below Tc) are shown in Figure 10. The reswelling kinetics of all the MG gels are similar. All these gels reach their equilibrium swollen state in just 1 min which could rarely be found in most of the former research works. For gel NG30, although the deswelling rate is very fast, the reswelling rate is not so rapid. It is difficult for water molecules to diffuse into the matrix of NG gels because of their compact structure at equilibrium shrunken state. The rapid deswelling-reswelling kinetics of MG gels are contributed to the macroporous structure.32
Conclusions Figure 9. Deswelling kinetics of the gels at 45 °C from the equilibrium swollen state at 15 °C.
at the temperature both above and below the Tc. The ratio of gel NG30 is a little higher than that of NG0. Great increase of SRs can be seen for all of the MG gels (MG0, MG10, MG20, and MG30) because of their macroporous structures. The macroporous structure leads the gels to absorb a greater amount of water at swollen state. At the shrunken state above Tc, pores cannot be occupied entirely by the hydrophobic cross-linked polymer chain, as NG gels and the pores of certain size that can hold a part of water still exist,34 and so the SRs of MG gels are much higher than that of NG gels in the shrunken state. Although the sizes of the pores are different according to the above discussion, the difference of SR between MG gels that were synthesized with various amounts of PVA is not so significant. Deswelling and Reswelling Kinetics. The deswelling kinetics of gels after a temperature jump from 15 °C (below Tc) to 45 °C (above Tc) are shown in Figure 9. The deswelling rate of gel NG0 is very slow, as it can only lose less than 40% of water even after 2 h. When PVA was involved to form a semi-IPN, the deswelling rate of gel NG30 is very fast because the hydrophilic PVA chains act as water-releasing channels when deswelling
The paper proposed a novel method for controlling the pore size of a kind of macroporous PNIPA hydrogels by adding various amount of PVA. Macroporous PNIPA hydrogels were formed as a result of a heterogeneous initiation system. The morphology of the resulted hydrogels was studied by both optical microscope and SEM. Moreover, the pore size and its distribution were examined by MIP. All the results indicated that size of the pores decreased with the increase of the amount of PVA added. The size of the aggregates of the heterogeneous initiator DDBAPS that were formed in situ in PVA aqueous solutions of various concentrations was measured by DLS. PVA was able to prevent the DDBAPS aggregates from conglomeration when the heterogeneous initiation system was formed, and various size of the aggregates resulted in various size of the pores. Furthermore, the SR and deswelling/reswelling kinetics showed that the response rates of the macroporous hydrogels that were synthesized in the presence of PVA were very fast whether the formed pores were larger or smaller. The adjustable porous property would extend the potential applications of the hydrogels. LA8038939 (39) Zhang, J. T.; Cheng, S. X.; Zhuo, R. X. Colloid Polym. Sci. 2003, 281, 580–583.
