Journal of Membrane Science 238 (2004) 6573

Formation of poly(l-lactic acid) microfiltration membranes

via thermally induced phase separation
Takaaki Tanaka a, , Douglas R. Lloyd b
a
b

Department of Materials Science and Technology, Niigata University, Niigata 950-2181, Japan
Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712, USA

Received 10 November 2003; received in revised form 16 March 2004; accepted 16 March 2004
Available online 11 May 2004

Abstract
Microfiltration membranes of poly(l-lactic acid) (PLLA) were prepared from PLLA1,4-dioxanewater solutions via the thermally induced
phase separation process. Ternary phase diagrams for this system, determined at 10, 48, and 80 C, indicate that essentially polymer-free
droplets form in a matrix phase of PLLA1,4-dioxanewater solution. Rapid solidification of the PLLA after the initial liquidliquid phase
separation was necessary to obtain membranes with open pores at the membrane surface and low permeation resistance. Using filtration of
cell suspensions, the effective pore size of the best membrane formed in this study was found to be between 0.6 and 4.4 m.
2004 Elsevier B.V. All rights reserved.
Keywords: Poly(l-lactic acid); Microfiltration membrane; Phase separation; Biodegradable plastics; Permeability

1. Introduction
Until the late 1980s, application of poly(l-lactic acid)
(PLLA) was limited to medical uses because of its high price.
However, decreases in the production cost of l-lactic acid
and improvements in the polymerization process have led to
the commercial-scale production of PLLA for non-medical
applications, such as packaging films, containers, and fibers
[1,2]. PLLA offers two distinct advantages over conventional
polymers. First, PLLA is produced from a monomer that can
be produced by lactic acid bacteria using agricultural products and by-products. Therefore, unlike most commercial
polymers, the cost of PLLA is not dependent on the production and price of oil. Since the feedstock for the polymer is
annually renewable, the use of PLLA will help reduce the
emission of fossil fuel-derived CO2 [1]. Second, PLLA is
biodegradable in vivo [3], in the environment [4] and in compost [2]. High molecular weight PLLA is rarely effected by
fungi, mold, or other microbes at ordinary temperatures, but
it can readily be converted into compost in municipal compost facilities at high temperatures (5570 C) and high hu Corresponding author. Tel.: +81-25-262-7495;
fax: +81-25-262-7495.
E-mail address: tctanaka@eng.niigata-u.ac.jp (T. Tanaka).

0376-7388/$ see front matter 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.memsci.2004.03.020

midity. Upon disposal, PLLA is degraded initially by chemical hydrolysis, not microbial attack. Oligomers of lactic acid
serve as a catalyst for the hydrolysis of PLLA in abiotic
degradation [3], while some enzymes [5] and microorganisms [4] enhance the rate of the degradation of the polymer.
To help establish a green sustainable society, wider use of
biodegradable polymers such as PLLA is desired. If PLLA
is used for microfiltration membranes in food and biochemical industries, where microfiltration is a key processes of
clarification and cell recovery, the membrane can be composted after use.
Porous PLLA membranes have been developed previously to serve as the scaffold for human cell growth in tissue
engineering and as the support for the controlled release of
medicines. These porous structures were made by a variety
of methods: use of a porogen, dry phase inversion, immersion precipitation, and thermally induced phase separation.
In the porogen method, a solution of PLLA in chloroform or
methylene chloride containing sieved salt crystals (sodium
citrate, NH4 Cl, NaCl) is cast on a plate. The film formed
after the evaporation of the solvent was washed with water.
The spaces occupied by the salt crystals turn into the pores
[3,6,7]. These porous membranes are suitable for scaffolding
of mammalian cells but not for microfiltration membranes
because the pores are several hundred micrometers. In the

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dry phase inversion method, porous membranes are made by

evaporating the solvent from a solution of PLLA in acetone
or methylene chlorideethyl acetate [8,9]. In the preparation
of porous PLLA structures by the immersion precipitation
method, 1,4-dioxane, chloroform, N-methyl pyrrolidone, or
acetone was used as the solvent while water, methanol, or
ethanol was used as the nonsolvent in a ternary casting solution [10,11]. Thermally induced phase separation [12,13]
has also been applied to make porous PLLA membranes.
In this method 1,4-dioxane [14,15] or 1,4-dioxane plus water [16,17] served as the diluent. Solutions of PLLA were
prepared at an elevated temperature, cooled to induce phase
separation, and then freeze dried. Alternatively, solutions of
PLLA in phenol, naphthalene [18], or methylene chloride
plus ethyl acetate [19,20] were heated, cooled to room temperature, and then dried to produce PLLA foams. Porous
PLLA structures have also been obtained by blending PLLA
and poly(ethylene oxide) in chloroform, drying off the chloroform, and extracting the poly(ethylene oxide) with water
[21]. In these previous studies the morphology of the membranes have been observed by scanning electron microscopy
and the pore-size distribution of some of the membranes
have been measured by mercury porosimetry. However,
these membranes have not yet been used for microfiltration.
In the study reported here, microfiltration membranes
were prepared from ternary mixtures of PLLA1,4-dioxane
water via the thermally induced phase separation method,
and they were characterized for permeation resistance and
retention of microbial cells.

2. Experimental
2.1. Materials
PLLA was a gift from Shimadzu Corp. (Kyoto) and Toyota Motor Corp. (Nagoya). The weight average molecular
weight, melting point, and glass transition temperature were
1.87 105 (Mw /Mn = 2.4), 175.4 C, and 62.8 C, respectively, according to the data sheet from the manufacturer. Analytical grade 1,4-dioxane (bp = 101.4 C, mp = 11.8 C)
was used without further purification.
2.2. Phase diagrams
As mentioned above, 1,4-dioxane (solubility parameter =
10.0 cal0.5 /cm0.5 [20.5 MPa0.5 ]) has been used to dissolve
poly(lactic acid) (solubility parameter = 10.010.3 cal0.5 /
cm0.5 [20.521.1 MPa0.5 ]) [23] for the preparation of membranes. The cloud point of PLLA1,4-dioxane system decreases from the freezing point of 1,4-dioxane (11.8 C)
as the PLLA concentration is increased [15]. This type of
phase diagram indicates that solidliquid phase separation
will occur when the solution is thermally quenched. However, when water (which is miscible with 1,4-dioxane, but is
a non-solvent for PLLA) is added to the PLLA1,4-dioxane

solution, the shape of the phase diagram changes to yield a

two-phase liquidliquid region [16,17,22]. Because water is
a non-solvent for PLLA but is miscible with 1,4-dioxane, it
has also been used as the coagulation bath in the preparation of PLLA porous materials via immersion precipitation
(nonsolvent induced phase separation) [10,22,24,25].
PLLA was dissolved in a 1,4-dioxanewater mixture in a
100 or 125 cm3 flask, sealed with a cork stopper which had
been covered with aluminum foil and polytetrafluoroethylene tape. The polymer concentration and the water content in the diluent were 120 and 1115 wt.%, respectively.
PLLA was first dissolved in 1,4-dioxane at 8090 C on a
stirrer/hot plate (Model PC-420, Corning, New York, NY)
and then water was added. After dissolution, the solution
was kept at 80 C for more than 30 min by placing the sealed
flask in an oven. The solution was then placed in a water
bath at 2080 C and held at that temperature for a period
of ten minutes. The cloud point temperature was defined in
this study as the temperature at which the solution turned
cloudy during the 10 min period, having been clear during
the 10 min hold time at a temperature 1 C above the cloud
point temperature. The ternary phase diagram was determined by the method shown by van de Witte et al. [22].
Tie lines at 48 C were determined as follows. A mixture containing 2.00 g of PLLA, 40.80 g of 1,4-dioxane, and
7.20 g of water (total weight = 50.00 g) was prepared at
80 C in a 100 cm3 flask as described above. After becoming clear and homogeneous, the mixture was moved to a
water bath at 48 C and kept there for 30 min. It was then
kept at 48 C in an incubator for 1224 h. During this time
the mixture separated into two clear but distinct phases. The
top (polymer-lean) phase was recovered with a pipette into
a glass beaker in the incubator. The pipette and beaker were
preheated at 48 C for more than 30 min before use. The
weight of the bottom (polymer-rich) phase was calculated
from the difference between the weight of the total sample
and the top phase. Since the phase diagram indicated that
the top phase was essentially polymer-free, it was assumed
that all of the polymer was in the bottom phase. Therefore,
the polymer concentration in the bottom phase was calculated from the initial mass of the polymer in the mixture and
the mass of the bottom phase. The polymer concentration
so determined was used to represent the bottom phase on
the binodal at 48 C. The tie line was drawn to pass through
the composition of the bottom phase and the initial composition (not shown) and is extended to the polymer-free axis.
Another tie line was determined with a mixture containing
5.00 g of PLLA, 38.70 g of 1,4-dioxane, and 6.30 g of water.
2.3. Membrane formation
PLLA membranes were prepared in an apparatus (Fig. 1)
composed of three stainless steel pie pans (22.8 cm in diameter, G&S Metal Products Co., Cleveland, OH). The apparatus was preheated in an oven for 15 min before use. A
PLLA solution (10 wt.%) in a mixed diluent of 1,4-dioxane

T. Tanaka, D.R. Lloyd / Journal of Membrane Science 238 (2004) 6573

67

Fig. 1. Apparatus for membrane preparation.

and water (87:13) was kept in a sealed flask at 80 C for

more than 30 min. The solution (approximately 40 cm3 ) was
poured into the bottom pan. The solution was covered with
the middle pan and kept at 80 C for 5 min. The distance between the bottom and middle pan was maintained at 0.8 mm
through the use of four metal spacers. A third pan was placed
over the middle pan as shown and the solution was kept
at 80 C for 10 min. The top pan protected the middle pan
from any thermal conduction effects caused by the air in the
room. The apparatus was cooled for 5 min in a water bath
at 50 C and then quenched to 0 C in an ice water bath for
1 h. The gel formed by this method was washed with chilled
water to remove the diluent. After the three times of washing (100, 800 cm3 , and 1 dm3 of water) the membranes did
not smell of 1,4-dioxane. The resulting porous membranes
were kept in water before characterization.
2.4. Scanning electron microscopy (SEM)
The wet membrane was immersed in liquid nitrogen and
then fractured. It was mounted vertically on a sample holder.
The surface of the sample was coated with goldpalladium
using a sputter coater (EMS 575, Electron Microscopy Science, Fort Washington, PA). A scanning electron microscope
(S-4500II, Hitachi, Tokyo) with an accelerating voltage of
15 kV was used to examine the membrane cross-sections
and surfaces.

of L broth in a 2 dm3 flask. The cells were recovered by

centrifuge and suspended in the same volume of distilled
water. The cell concentration was 3.5 kg-wet/m3 , which corresponds to 1.0 kg-dry/m3 . The cell size was 1.060.20 m
in length and 0.63 0.04 m in diameter as determined
by measuring the length and diameter of 100 cells under a
scanning electron microscope.
3. Results and discussion
3.1. Phase diagram
Fig. 2(a) shows the effect of the PLLA concentration
on the cloud point temperature of the solutions of PLLA
in 1,4-dioxane containing water at different concentrations
(1115 wt.%). The cloud point temperature increased linearly with increasing polymer concentration for each water
content. It also increased linearly when the water content
in the diluent was increased at the same PLLA concentration (Fig. 2(b)). The phase behavior of the PLLA1,4dioxanewater system was similar to the results reported by
van de Witte et al. [22] for the same system, although the
cloud point temperatures reported here are slightly higher.

2.5. Filtration experiments

A filtration cell (Amicon model 8010, 4.1 cm2 , Millipore,
Bedford, MA) was used without its stirrer for dead-end filtration experiments. Water was used to measure the permeation resistance of membranes. The filtration was performed
at a transmembrane pressure drop of 30 kPa and at 2225 C,
where the viscosity of water is 1 103 Pa s. Microbial
cells of bakers yeast (Fleishmanns active dry yeast, Fenton, MO) and Escherichia coli MC4100 were used to examine the retention of microorganisms by the membranes. The
yeast cells were suspended in distilled water at a concentration of 10 kg/m3 as dry yeast powder, which corresponds to
a cell concentration of 24 kg-wet/m3 and 7 kg-dry/m3 . A cell
size of (5.6 1.1) (4.4 0.8) m was determined by measuring the long and short axes of 100 cells under an optical
microscope. The E. coli was cultivated for 12 h in 400 cm3

Fig. 2. Cloud point temperatures of PLLA1,4-dioxanewater system.

Dependence on the PLLA concentration (a) and water content in diluents
(b).

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T. Tanaka, D.R. Lloyd / Journal of Membrane Science 238 (2004) 6573

Fig. 3. Ternary phase diagram of PLLA1,4-dioxanewater system. Broken lines are tie lines at 48 C. The black rhombus shows the composition of the mixture of 10 wt.% PLLA in a mixed diluent of 87 wt.%
1,4-dioxane and 13 wt.% water.

There is a possibility of hydrolysis of PLLA in

1,4-dioxane containing water at 80 C. The cloud points
will decrease when the molecular weight was lowered by
the hydrolysis [17,26]. However, the effect will be small on
the cloud points in this study since the temperatures did not
change when we checked some of them within 1 h.
Ternary phase diagrams of the PLLA1,4-dioxanewater
system at different temperatures (Fig. 3) were obtained
from the data in Fig. 2(b) by the method reported by
van de Witte et al. [22]. The binodal shifted from the
solvent-rich area toward the nonsolvent-rich area with increasing temperature, indicating a decrease in system compatibility with decreasing temperature. Fig. 4 schematically
shows the mechanisms of phase separation for a ternary
polymersolventnonsolvent system undergoing thermally
induced phase separation. As the homogeneous solution
is cooled, it starts to demix into two liquid phases at the
cloud point temperature. When the polymer concentration
is greater than the critical point concentration, droplets
of the polymer-lean phase form in the ternary mixture at
the cloud point temperature. In the system reported here
(see Fig. 3), the polymer concentration of the critical point
is less than 1 wt.% PLLA for temperatures in the range
1080 C. Thus, the PLLA1,4-dioxanewater system undergoes liquidliquid TIPS and should produce a cellular
porous membrane structure.

Fig. 4. Thermally induced phase separation in a ternary system: (a) phase

diagram on the tie line in (b); (b) isothermal ternary phase diagram at
the cloud point temperature.

membranes (109 to 1013 m1 as calculated from typical

reported permeability values of 1104 gal ft2 per day psi1
[27] with water of viscosity 1 103 Pa s at room temperature).
Fig. 6 shows the dependence of the membrane resistance
on the temperature at which a solution of 10 wt.% PLLA
in 1,4-dioxane containing 13 wt.% water was kept for 5 min
before quenching. The resistance greatly decreased when the
solution was kept at 5052 C before quenching. The reason
for this behaviour is discussed in the next section.

3.2. Membrane permeability

Fig. 5 shows the permeability of PLLA membranes
formed by different ternary mixtures of PLLA1,4-dioxane
water. The permeation resistance was independent of the
water content in the diluent when the PLLA concentration
was 10 wt.%. The resistance was lower than that of the
membrane prepared from a solution containing 12 wt.%
PLLA. However, these resistances are higher than those
of commercially available microfiltration and ultrafiltration

Fig. 5. Dependence of the membrane resistance on the water content in

diluent.

T. Tanaka, D.R. Lloyd / Journal of Membrane Science 238 (2004) 6573

Fig. 6. Dependence of the membrane resistance on the temperature before

quenching: PLLA = 10 wt.%; water content in diluent = 13 wt.%.

3.3. Membrane structure

Figs. 79 show the structure of membranes prepared
from a solution of 10 wt.% PLLA in 1,4-dioxane containing 13 wt.% water but with different thermal histories. The

69

membranes were prepared as described in Section 2.3, but

with different intermediate temperatures. Specifically, the
membranes were prepared by three methods. In Method A,
the assembly shown in Fig. 1 was quenched directly from
80 C into ice water. The membrane is shown in Fig. 7.
In Method B, the assembly was lowered from 80 to 50 C
where it was held for 5 min and then quenched in ice water. The membrane is shown in Fig. 8. In Method C, the
intermediate hold temperature was 30 C. The membrane
is shown in Fig. 9. Each figure shows the cross-section
(overview in (a), near the top surface in (b), and at the center
in (c)) and the top surface (in (d)). Micrographs corresponding to (b) and (d) taken at the bottom of the sample were
similar to those taken at the top and are therefore not shown
here. The cell size in the central part of the membranes
prepared by Methods A and B (Figs. 7(c) and 8(c)) were
essentially the same, with cells ranging from 3 to 10 m.
However, the surface and cross-section near the surface were
significantly different for these two thermal histories. The
cells were greatly deformed and the pores were closed near
the top surface of the membrane prepared by Method A
(Fig. 7(b) and (d)), while the cells near the surface were
open like those in the central part of the membrane when the

Fig. 7. PLLA membrane prepared by quenching 10 wt.% PLLA solution in 1,4-dioxane containing 13 wt.% water from 80 to 0 C. (a)(c) Cross-sections
(the top side is on the left-hand side): (a) overview; (b) near the top side; (c) near the center. (d) The top surface.

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T. Tanaka, D.R. Lloyd / Journal of Membrane Science 238 (2004) 6573

Fig. 8. PLLA membrane prepared by quenching 10 wt.% PLLA solution in 1,4-dioxane containing 13 wt.% water from 50 to 0 C: (a)(d) the same as
in Fig. 7.

membrane was prepared by Method B (Fig. 8(b) and (d)).

That is, Method A produces significant anisotropy in the
sample while Method B produces a structure more closely
approximating isotropic.
To explain the differences between Methods A and B, a
series of quench experiments were conducted to monitor the
temperature of the solution contained in the assembly shown
in Fig. 1. In these experiments, 40 cm3 of water was placed
in the assembly rather than polymer solution and the temperature was monitored using a thermocouple as the assembly
was quenched in ice water. Fig. 10 shows the temperature
of the water during the quench. In both cases the temperature decreases rapidly and then reaches a final steady-state
temperature equal to the surrounding ice water. Fig. 10 has
a horizontal line at 48 C, which is the phase separation
temperature for the PLLA1,4-dioxanewater system used
to make the membranes shown in Figs. 79. Fig. 10 also
has a horizontal line at 7 C, which is the solidification temperature of PLLA in this ternary system as explained in
the next paragraph. The membrane prepared via Method A
does not phase separate until 40 s after the quench and it
spends approximately 100 s between the time of phase separation and solidification. On the other hand, the membrane

prepared via Method B phase separates almost immediately

upon quenching and solidifies after 40 s. It is speculated that
the droplets of polymer-lean phase deformed at the stainless surfaces during the prolonged liquid period allowed in
Method A and resulted in closed cells upon solidification.
Thus, the permeation resistance of the membrane prepared
by Method A was much higher than that prepared by Method
B. This deformation of droplets at the metal surface may be
associated with spreading or wetting phenomenaa point
that needs to be explored further in future research.
To provide the PLLA solidification temperature indicated
in Fig. 10, a series of experiments were conducted. After
dissolving 10 wt.% PLLA in 1,4-dioxane containing 13 wt.%
water at 80 C, 3 cm3 of the solution was placed in a 125 cm3
flask where it formed a thin layer on the bottom of the flask.
The flask was capped with a stopper and transferred from an
80 C oven to a water bath at a predetermined temperature.
When placed in a bath at 10 C the solution became cloudy,
but remained fluid for more than 9 min. When the flask was
placed in a bath at 8 C, it solidified within 9 min, while it
took only 3 min in a 7 C bath. These results indicate that
the solidification rate is extremely sensitive to temperature,
especially around 7 C.

T. Tanaka, D.R. Lloyd / Journal of Membrane Science 238 (2004) 6573

71

Fig. 9. PLLA membrane prepared by quenching 10 wt.% PLLA solution in 1,4-dioxane containing 13 wt.% water from 30 to 0 C: (a)(d) the same as
in Fig. 7.

The pore size of the membrane prepared by holding the assembly at 30 C before quenching (Method C, Fig. 9(a)(c))
was 1030 m. In this case, the polymer-lean phase droplets
formed and coalesced during the pre-cooling at 30 C. For

the reasons outlined above, this prolonged period within the

two-phase region allowed the droplets to distort and a dense
polymer layer to form near both the top surfaces (Fig. 9(b)),
which resulted in high permeation resistance.
The structures shown in Figs. 79 and the dependence of
the membrane resistance on the temperature before quenching (Fig. 6) suggest that rapid solidification of the PLLA after phase separation is necessary to obtain open pores at the
membrane surfaces. This statement is in keeping with the
observations made when studying structure difference obtained using the immersion precipitation method of making
membranes [28], in which delayed demixing of a polymer
solution in a coagulation bath forms a nonporous layer on
the membrane surface while instantaneous demixing results
in open pores on the surface.
3.4. Filtration of microbial cell suspensions

Fig. 10. Thermal history of liquid within membrane preparation apparatus.

The temperature was measured with 40 cm3 of water at the center of the
top surface of the middle pan.

Suspensions of bakers yeast and E. coli cells were filtered with the membrane prepared by Method B to evaluate
it as a microfiltration membrane. Fig. 11(a) shows the permeation flux for the filtration of the yeast cell suspension,

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T. Tanaka, D.R. Lloyd / Journal of Membrane Science 238 (2004) 6573

giou of The University of Texas at Austin for the cultivation

of E. coli cells.

References

Fig. 11. Permeation flux in microfiltration of yeast cell suspension with

a PLLA membrane: (a) permeation flux; (b) a plot of reciprocal of
permeation flux vs. permeation volume per unit filtration area. Cell
concentration = 24 kg-wet/m3 ; transmembrane pressure = 29 kPa.

for which a transparent permeate was obtained. The yeast

cells were recovered 96% on the membrane. The change
in permeation flux with time was converted to a plot of
the reciprocal of the flux versus the permeate volume per
unit filtration area (Fig. 11(b)). The linear relationship between the reciprocal of flux and the permeate volume shows
that the filtration proceeded according to the cake filtration
model [29]. On the other hand, E. coli cells were not retained by the membrane (the recovery on the membrane =
0%). These results indicate that the effective pore size of the
membrane was between the size of the yeast (ellipsoidal,
4.4 m in short diameter) and E. coli (rod-shaped, 0.6 m in
diameter).

4. Conclusions
PLLA microfiltration membranes were prepared from
PLLA1,4-dioxanewater solutions via the TIPS process.
Quick solidification of the PLLA in the polymer-rich phase
after liquidliquid phase separation was necessary to obtain
membranes with low permeation resistance. The effective
pore size of the membrane formed using the thermal history
described as Method B in this study was between 0.6 and
4.4 m.

Acknowledgements
The authors thank Shimadzu Corp. and Toyota Motor
Corp. for the kind gift of poly(l-lactic acid). The study was
partially supported from the grant of the Niigata Engineering Promotion Inc. and Grants-in-Aid (15560673) for Scientific Research from the Japan Society for the Promotion
of Science, Ministry of Education, Culture, Sports, Science,
and Technology, Japan, to T. Tanaka. We thank Dr. Yasuaki
Kawarasaki of Nagoya University and Prof. George Geor-

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