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An Injection Molding Process for Manufacturing Highly Porous

and Interconnected Biodegradable Polymer Matrices for Use


as Tissue Engineering Scaffolds
Adam Kramschuster, Lih-Sheng Turng
Polymer Engineering Center, Department of Mechanical Engineering, University of Wisconsin-Madison, Madison,
Wisconsin 53706-1572

Received 21 April 2008; revised 1 May 2009; accepted 15 July 2009


Published online 2 December 2009 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.b.31523

Abstract: In this research, injection molding was combined with a novel material
combination, supercritical fluid processing, and particulate leaching techniques to produce
highly porous and interconnected structures that have the potential to act as scaffolds for
tissue engineering applications. The foamed structures, molded with polylactide (PLA) and
polyvinyl alcohol (PVOH) with salt as the particulate, were processed without the aid of
organic solvents, which can be detrimental to tissue growth. The pore size in the scaffolds is
controlled by salt particulates and interconnectivity is achieved by the co-continuous blending
morphology of biodegradable PLA matrix with water-soluble PVOH. Carbon dioxide (CO2) at
the supercritical state is used to serve as a plasticizer, thereby imparting moldability of blends
even with an ultra high salt particulate content, and allows the use of low processing
temperatures, which are desirable for temperature-sensitive biodegradable polymers.
Interconnected pores of 200 lm in diameter and porosities of 75% are reported and
discussed. ' 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 92B: 366376, 2010
Keywords:
facturing

microcellular injection molding; tissue engineering; scaffolds; porous; manu-

INTRODUCTION
Tissue engineering is an interdisciplinary eld aimed at the
development of biological substitutes that restore, maintain,
or improve tissue function.1 A highly porous biodegradable
scaffold is essential to accommodate mammalian cells and
guide their growth in three dimensions.2 In the past, natural
and synthetic polymers have routinely been used as substrates to provide this temporary scaffolding for transplanted
cells as they excrete their extracellular matrix (ECM) and
form new tissues or organs.14 Synthetic polymers offer several advantages over natural polymers such as collagen and
brin. They can be prepared in a reproducible manner in
almost unlimited quantities, and their physical, chemical,
and mechanical properties may be easily altered by chemical
modications. In addition, they can be easily processed with
conventional polymer processing equipment.5 Some common synthetic biodegradable polymers currently used as
scaffolding materials include polylactide (PLA) and polyglycolide (PGA), as well as their copolymers, and polycaprolactone (PCL).24 Myriads of new materialsincluding

tyrosine-derived polycarbonates and trimethylene carbonatebased materialsare also being explored as alternative synthetic polymers for tissue engineering scaffolds.56
The function of tissue engineering scaffolds is to direct
the growth of cells migrating from surrounding tissue (in
the case of scaffold-guided regeneration) or seeded within
the porous structure of the scaffold.3 The scaffold must
provide temporary support for cell adhesion, proliferation
and differentiation, nutrient transport, and the excretion of
waste while the cells secrete their own extracellular matrix
(ECM). Ideally, a scaffold should have the following characteristics: (1) a three-dimensional and highly porous structure with an interconnected pore network for cell growth
and ow transport of nutrients and metabolic waste; (2) be
biocompatible and bioresorbable with a controllable degradation and resorption rate to match cell/tissue growth in
vitro and/or in vivo; (3) have suitable surface chemistry for
cell attachment, proliferation, and differentiation; and (4)
have mechanical properties to match those of the tissues at
the site of implantation.7

Porosity, Pore Size, and Interconnectivity


Correspondence to: L.-S. Turng (e-mail: turng@engr.wisc.edu)
Contract grant sponsor: NSF; Contract grant number: DMI-0544729
' 2009 Wiley Periodicals, Inc.

366

Highly porous scaffolds are required to allow for cells to


inltrate and attach to the scaffold, to provide a high sur-

INJECTION MOLDING PROCESS FOR MANUFACTURING HIGHLY POROUS POLYMER MATRICES

face area-to-volume ratio for polymer-cell interactions, and


to obtain minimal diffusion constraints during cell culture.
Past research has stated that a scaffold porosity of greater
than 90% is important for tissue engineering applications.8
However, much of the basis for this is due to early methods (namely solvent casting/particulate leaching) being
unable to achieve high interconnectivity at porosities less
than 90%. In fact, researchers have used scaffolds with
porosities ranging from 55 to 74% for bone growth due to
better and more controllable mechanical properties at lower
porosities.911
The optimal pore size for tissue regeneration is dependent on the type of tissue.2 However, even for bone regeneration, no consensus regarding the optimal pore size in
scaffolds has been determined. Pore sizes ranging from 50
to 710 lm have been suggested for bone regeneration, with
many studies stating that macropores in the range of 150 to
350 lm are ideal.2,12,13 Therefore, macropores on the order
of hundreds of microns with an interconnecting network on
the order of tens of microns has been deemed suitable for
tissue regeneration. At the same time, the effects of surface
chemistry, culture conditions, mechanical properties, and
degradation rate play a large role in tissue formation, and
will be discussed further.

Biocompatibility and Degradation

The material used for the polymeric scaffold must exhibit


good biocompatibility, meaning that it must not elicit an
unresolved inammatory response nor demonstrate extreme
immunogenicity or cytotoxicity.14 For example, PLA
hydrolyzes to lactic acid, which is a normal byproduct of
muscle contractions in animals. The lactic acid is then further metabolized through the tricarboxylic acid cycle and
excreted as carbon dioxide and water.15 The issue of biocompatibility is directly linked to the degradation of the
material as well. For instance, if the degradation rate of the
polymer is too fast, not only will it cease to provide the
necessary mechanical support for the tissue, the surrounding tissue cannot eliminate the acid byproducts, resulting in
an inammatory or toxic response.5,15 As discussed in Ref.
16, some synthetic biodegradable polymers can be tailored
to elicit specic degradation rates based on their composition (e.g., PLGA).

Surface Chemistry

The nature of the polymer surface can affect the ability of


cells and proteins to attach to its surface, proliferate, and
differentiate. Polymers like PLA and PGA are relatively
hydrophobic, and it is difcult to efciently and evenly
seed cells into porous matrices fabricated from these polymers.17,18 The use of hydrophilic polyvinyl alcohol
(PVOH)19 and many other methods of surface modication
can be found in Refs. 2023 and the references cited
therein.
Journal of Biomedical Materials Research Part B: Applied Biomaterials

367

TABLE I. Mechanical Properties of Human Tissues

Cancellous bone
Cortical bone
Cartilage
Ligament
Tendon

Tensile
Strength
(MPa)

Compressive
Strength
(MPa)

Youngs
Modulus
(MPa)

8
60160
3.710.5
1346
24112

412
130180
n/a
n/a
n/a

50100
330 3 103
0.715.3
65541
1432310

Adapted from Refs. 2 and 24.

Mechanical Properties

The mechanical properties of the scaffold fabricated should


closely match the mechanical properties of the neotissues
to be generated in order to provide support during the initial stages of tissue growth. If the mechanical properties are
too low, the scaffold could be deformed or crushed, leading
to deformed tissue growth, or no tissue growth at all. At
the same time, if the mechanical properties are too high,
the cells may not be subjected to the proper in vivo conditions needed to support cell growth. Additionally, especially in load-bearing instances, scaffold mechanical
properties that exceed that of the surrounding bone may
lead to stress-shielding, a condition where the surrounding bone experiences a decrease in density. However, this
is more prevalent with permanent implants. The mechanical
properties of several tissues, including bone and cartilage,
can be found in Table I.2,24

Scaffold Processing

Many methods for producing scaffolds using synthetic biodegradable polymers have been developed and extensive
reviews detailing these methods are available.25,12,13 However, the majority of current scaffold fabrication techniques
can be described as batch processes or use organic solvents,
which can be detrimental to cell survival and tissue
growth.13 While these techniques may be adequate and
essential for studying the effects of the substrate material,
porosity, pore size, interconnectivity of the pores, mechanical and chemical properties, growth factors, and nutrient
transport on the effects of tissue regeneration both in vitro
and in vivo, they do not address the need for cost-effective
manufacturing processes to meet patient needs. The ability
to mass produce highly porous, highly interconnected scaffolds with complex geometries is essential to provide offthe-shelf availability.25
Plastic injection molding has long been used to costeffectively manufacture complex 3D parts. Mechanical pencils, automotive door panels, computer and cell phone
housings, sunglasses, optical lenses, and many medical
devices are all examples of injection-molded parts. The
low-cost manufacturing, repeatability, and design exibility
inherent in the injection molding process make it an ideal
process to suit this wide variety of industries. These char-

368

KRAMSCHUSTER AND TURNG

acteristics also make injection molding an ideal manufacturing process to create 3D scaffolds, as long as high porosity (e.g., maximum porosities of 80% have been shown
to be desirable for orthopedic applications12,26) and interconnectivity can be imparted into the nished product.
Recently, researchers have been striving to develop methods by which these characteristics can be imparted into
complex 2D and 3D structures via extrusion2729 and injection molding,3034 respectively, which may have the potential to act as tissue engineering scaffolds. However, the
techniques that have been explored for 3D structures have
either fallen short of scaffold requirements, such as porosity and interconnectivity,3033 or they involve the use of organic solvents,34 which may be harmful to cells. This
research aims to provide a novel method using microcellular injection molding (to be discussed below) for the production of biodegradable scaffolds with high porosity and
interconnectivity without the use of organic solvents.
In this research, polylactide (PLA) was compounded
with water-soluble polyvinyl alcohol (PVOH) and sodium
chloride (NaCl) to create a composite blend. Utilizing
microcellular injection molding and subsequent leaching of
the samples in water resulted in PLA foams of over 75%
porosity with high interconnectivity.

and injection molding applications, this material was used


for subsequent compounding and injection molding experiments. AqualSol 116 has a specic gravity of 1.27, a melting temperature of 1848C, and a melt ow index around
10 g/10 min (2008C/5 kg).
Sodium Chloride. Based on previous batch processes
described in Refs. 3742, sodium chloride (NaCl) was used
as the particulate. It can be easily size-reduced and sieved
to the desired size range, it can be easily dissolved in
water, and its melting point of 8018C ensures that it will
not melt at normal polymer processing conditions used for
this research (under 2008C). The NaCl used for these
experiments was reagent grade, purchased from Fisher Scientic with a specic gravity of 2.165.
Carbon Dioxide. Carbon dioxide (CO2) was chosen as
the benign blowing agent for the microcellular injection
molding process. It has a much higher solubility than nitrogen in most polymers and allows for larger cell sizes and a
greater density reduction when used in the microcellular
injection molding process.43

Experiments

MATERIALS AND EXPERIMENTS


Materials

Salt Reduction and Sieving. The NaCl particles were


size reduced using a Wiley mill and a screen with 1 mm diameter holes. Once the particles were size reduced, they were
sieved to a size range of 150 to 300 lm using sieve screens
and a wet/dry sieve shaker (H-4328, Humboldt Mfg.).

Polylactide. Polylactide (PLA) was chosen as the biodegradable polymer to serve as the matrix material for this
research. Because of the extremely high cost of medical
grade poly(D,L-lactide) (up to thousands of dollars per
pound), nonmedical grade poly(D,L-lactide) (referred to
simply as PLA throughout this article) was used for this
research. The PLA used, NatureWorksTM PLA 3001D, is a
lactic acid copolymer based on 1.5% D-lactic acid and
98.5% L-lactic acid. It was purchased in pellet form from
NatureWorks LLC. It has a specic gravity of 1.24 and a
melt ow index around 15 g/10 min (1908C/2.16 kg). Its
glass transition temperature is 70 to 758C and its melting
temperature is 1678C.

Compounding. The PLA, PVOH, and NaCl were compounded using a Davis Standard twin screw extruder with a
screw diameter of 25 mm and an L/D ratio of 36.25. The
materials were loaded into separate gravimetric feed hoppers
to accurately meter the material at a constant feed rate of 40
lb/h for all materials combined. The end cap temperature
was set at 1858C and a screw rotation speed of 200 rpm was
used. Upon extrusion, the strands were cooled with compressed air and pelletized. The formulations compounded
and analyzed in this article can be found in Table II.

Polyvinyl Alcohol. In order to create a co-continuous


network to connect the pores in the PLA matrix, polyvinyl
alcohol (PVOH) was chosen as the sacricial water-soluble
polymer. In general, the water-soluble polymer selected
must have a similar melt temperature and be immiscible
with the chosen biodegradable polymer matrix. Previous
theoretical and experimental studies have shown that PLA
and PVOH form immiscible blends.35,36 Celvol 502 (Celanese Chemical Co.) supplied in granular form and AquaSol
116 (A. Schulman) supplied in pellet form were donated
for this research. Initial testing of co-continuity of the
PLAPVOH blends was performed with Celvol 502. Celvol
502 has a melting temperature of 1798C. Because AquaSol
116 is supplied in pellet form and is designed for extrusion

Microcellular Injection Molding. The injection molding


experiments were performed on an Arburg Allrounder 320S
with a 25 mm diameter screw and equipped with MuCell1
Technology (Trexel, Inc.) (cf. Figure 1). Microcellular
injection molding (or MuCell1) blends atmospheric gas
(usually nitrogen or carbon dioxide) at a high-pressure
supercritical state with the polymer melt to create a singlephase polymer-gas solution. To facilitate fast and homogeneous mixing of the gas and polymer, and to maintain the
single-phase solution prior to injection, the pressure inside
the barrel is generally kept around 200 bar. During injection, the sudden pressure drop triggers a thermodynamic
instability of the polymer-gas solution. As a result, the gas
starts emerging from the polymer-gas solution and forms
Journal of Biomedical Materials Research Part B: Applied Biomaterials

INJECTION MOLDING PROCESS FOR MANUFACTURING HIGHLY POROUS POLYMER MATRICES

369

TABLE II. Formulations Compounded in the Twin Screw


Extruder

Blend 1
Blend 2
Blend 3

Materials

Composition
(vol %)

NaClPLA
PLAPVOH
NaClPLAPVOH

41/59
67/33
60/20/20

numerous microscale cells. This process is similar to the


batch foaming processes described in Refs. 44 and 45
except that it is adapted to conventional injection molding
equipment. It was used by Leicher et al.32 in an attempt to
fabricate tissue engineering scaffolds with polyether-urethane. While this process can be used to impart porosity
into the molded part, the supercritical uid also lls the interstitial sites between polymer molecules, effectively
reducing the viscosity.4648 This enables the material to be
processed at much lower pressures and temperatures.
For these experiments, the pellets compounded in the
twin screw extruder were dried overnight at 558C to
remove any residual moisture. The materials were injection
molded with a maximum barrel temperature of 1858C and
a wt % SCF CO2 content of 2.2. The molded samples were
impact bars with dimensions of 166 mm by 12.9 mm by
4.8 mm. To study the repeatability of the results, at least
10 samples were injection molded and subsequently
leached under each material and process condition combination, and at least three specimens were tested and analyzed to ensure consistency of the results and to obtain the
standard deviation.
Leaching. After injection molding, the molded samples
were leached in deionized water for up to 48 h using the
setup depicted in Figure 2. The continuous supply of water
was necessary to ush the PVOH as it absorbed water and
swelled before dissolving. Select samples were removed
every 3 to 6 h for testing. A water pump (Via Aqua
1300A) continuously pumped water into the top of the res-

Figure 2. Schematic of the setup used for leaching the injectionmolded samples.

ervoir. The water exited the bottom of the reservoir and


cycled back through the pump. The water was changed every 6 h. Because of the lack of interconnectivity with the
NaClPLA formulation, these samples were cryogenically
fractured and then leached to observe the morphology. For
the PLAPVOH blend and NaClPLAPVOH composite
blend, the samples were leached and subsequently cryogenically fractured for analysis.
Scanning Electron Microscopy. The morphology of the
injection-molded samples was evaluated using a JEOL
JSM-6100 scanning electron microscope (SEM) with an
accelerating voltage of 15 kV. The samples were leached
and cryogenically fractured using liquid nitrogen and then
sputtered with gold for 120 s.
Thermogravimetric Analysis. The residual salt content
of the NaClPLAPVOH composite blends was analyzed
using a Perkin Elmer thermogravimetric analyzer (TGA).
The samples were heated from 50 to 7008C at a ramp
speed of 408C/min.
Porosity Calculation. The porosity (or void fraction) of
the leached samples was determined by weighing them and
measuring the dimensions of the weighed samples to obtain
the volume. Equation (1) was then applied to determine the
porosity.

Vf



qapp
1
3100
qPLA

where Vf is the void fraction or porosity of the sample,


qapp is the apparent density of the porous scaffold, and
qPLA is the known density of the matrix material (PLA 5
1.24 g/cm3).
RESULTS
Morphology

Figure 1. Schematic of the microcellular injection molding process


with characteristic morphology.
Journal of Biomedical Materials Research Part B: Applied Biomaterials

NaClPLA (4159 vol %). The samples were molded,


leached with water, cryogenically fractured, and examined
with SEM as described previously. Figures 3 and 4 clearly
show a lack of interconnectivity in the NaClPLA sample.
The outside edge of the sample is porous due to direct con-

370

KRAMSCHUSTER AND TURNG

Figure 3. The porous outside and center are due to direct contact
with water and gas foaming, respectively.

tact with the water during leaching and the center portion
of the sample has closed pores due to CO2 foaming associated with the microcellular injection molding (cf. Figure 3).
The porous skin surrounding the (mostly) solid center is
more clearly dened in Figure 4. Figure 5 shows a magnied view of a sample that was fractured and subsequently
leached. Therefore, the entire cross-section is directly
exposed to water, allowing for the entire surface to be dissolved leaving behind the pores due to the NaCl particles.
PLAPVOH (6733 vol %). Because of the lack of interconnectivity in the NaClPLA composites, the use of a
water-soluble polymer and PLA was proposed to connect
the NaCl particulates in the PLA matrix. As discussed previously, PLA and PVOH have been shown to be immiscible, though their ability to form a co-continuous blend

Figure 4. The porous outer edge and solid core are more clearly
dened.

Figure 5. Thin walls of PLA separate three pores left by direct


leaching of the NaCl particles.

needed to be determined for this research. PLA was compounded with Celvol 502 to form a 6733 vol % blend.
This material was leached and subsequently fractured.
Figure 6 shows a magnied SEM image of the cross section of an extruded strand. Porous channels ranging from 1
to 30 lm were formed throughout the entire cross section
of the part, with the majority of channel diameters less
than 5 lm.
In Figure 6, the edge of the cross section of the extruded
strand is also highlighted. Porous channels can be seen on
the outside of the strand that allowed for the entire leaching
of the sample. From these SEM images, it was determined
that PLA and PVOH form a co-continuous structure that
could be potentially used to create connecting channels
between NaCl particles to form a highly porous biodegradable scaffold.

Figure 6. Channels on the outside surface allowed for the dissolution of PVOH in the center of the part that did not come in direct
contact with water when rst placed in the leaching reservoir.
Journal of Biomedical Materials Research Part B: Applied Biomaterials

INJECTION MOLDING PROCESS FOR MANUFACTURING HIGHLY POROUS POLYMER MATRICES

Figure 7. Cross-section of the NaClPLAPVOH (602020 vol %)


composite blend showing what appears to be a fully leached surface with uniform porosity throughout the part.

371

NaClPLAPVOH (602020 vol %). Combining polyvinyl alcohol and particulate leaching with microcellular
injection molding resulted in a porous and fully interconnected sample, Figure 7. For the samples to be fully
leached, the PVOH would have had to form a continuous
phase throughout the PLA matrix to connect the NaCl particles. Evidence of this occurring can be seen in Figure 8.
Several magnied images of pores left behind by NaCl particles are shown with smaller pores (less than 10 lm) that
were left behind by the PVOH and possibly NaCl particles
that were broken down during processing (cf. Figure 9).
Figure 10 displays the effect of leaching time on the dissolution of NaCl and PVOH. In Figure 10(a), the sample
had not been leached (0 h). The voids in this part were due
to a combination of microcellular CO2 gas foaming and a
difference in thermal coefcients of expansion for NaCl
compared to PLA and PVOH. Visual observation of Figure
10 shows a disappearance of the solid core after 6 h, but it
is difcult to quantitatively determine when all of the salt

Figure 8. SEM showing the pores left behind by NaCl particles and the smaller channel diameters left behind by the PVOH that provided the
interconnected network for leaching.
Journal of Biomedical Materials Research Part B: Applied Biomaterials

372

KRAMSCHUSTER AND TURNG

Residual NaCl Content. TGA was used to quantitatively


determine the residual NaCl content of the 602020
NaClPLAPVOH composite blend as a function of leaching time (cf. Figure 12). After heating to 7008C, the only
remaining component of the composite blend was the
NaCl. After leaching for 18 h, the wt % NaCl was 3.8%
and reached a plateau of 3.4% after 24 h. This translates
to a vol % of 2.0% for a solid composite blend. However, the samples analyzed were highly porous as evidenced by the SEM images shown previously. Therefore,
the actual vol % of NaCl in the porous structure is much
lower than 2.0% and is a function of wt % NaCl and porosity. A 75% porous sample with a residual NaCl content
of 3.4 wt % has a vol % NaCl under 0.5%.
Porosity. The porosity of the 602020 vol% NaCl
PLAPVOH composite blend was calculated using Eq. (1).
The porosities as a function of leaching time for the 60
2020 NaClPLAPVOH composite blend are shown in
Figure 13. For samples leached 18 h or more, the porosity
reached 75%.

DISCUSSION
Morphology

Figure 9. SEM of the sieved NaCl particles (a) before compounding,


and (b) after compounding.

has been dissolved. This topic is quantitatively assessed in


the subsequent section.

NaCl Content

NaClPLA (4159 vol %). Previous research using the


solvent casting/particulate leaching (SC/PL) technique discussed in Refs. 3742 has shown that salt contents of less
than 90 vol % resulted in poor interconnectivity. However,
no published literature had previously examined the use of
particulate leaching with microcellular injection molding.
Therefore, this formulation served as a preliminary study
for the evaluation of this technique. The lack of interconnectivity in the NaClPLA samples was due to the salt particles becoming encapsulated in PLA during compounding
and injection molding. Figure 5 clearly shows thin walls of
PLA separating three pores left by NaCl particles. Had
these samples not been fractured prior to leaching, the lack
of interconnectivity in the sample would have prevented
these pores from being formed.

Blend Composition. Because of the different densities

PLAPVOH (6733 vol %). Washburn et al.27,28 origi-

of the NaCl, PLA, and PVOH, a set of equations was


solved simultaneously to determine the weight percent of
each material to obtain the desired composition. For a 60
2020 composite blend of NaClPLAPVOH, 72.13% of
the composite blend weight should be NaCl. Using TGA,
the NaCl content of the 602020 composite blend was
found to be 69.7 wt % (cf. Figure 11) or 57 vol %. This
deviation from the theoretical NaCl content can be attributed to two causes: (1) NaCl crystals were lost when the
extruded strands were pelletized due to the chopping action
of the pelletizer, or (2) the gravimetric feeders were not
100% accurate when metering the three materials into the
extruder.

nally proposed using a water-soluble polymer, polyethylene


oxide (PEO), and a biodegradable polymer, PCL, to create
co-continuous blends for tissue engineering scaffolds. A
subsequent leaching step in water leaves a porous matrix
that is fully interconnected. This technique and its improvements (including the incorporation of NaCl as a particulate)
were highlighted by Reignier and Huneault.29
No attempts at altering process conditions were made to
modify the channel diameters of the extruded PLAPVOH
blend. Previous research summarized by Sundararaj49
reported that the nal domain size is about one 1 lm for
the majority of uncompatibilized polymer blends, regardless of processing conditions. Part of the reason for this is
Journal of Biomedical Materials Research Part B: Applied Biomaterials

INJECTION MOLDING PROCESS FOR MANUFACTURING HIGHLY POROUS POLYMER MATRICES

373

Figure 10. Morphology as a result of varying leaching time: (a) 0 h, or not leached at all, (b) 3 h, (c) 6 h, and (d) 30 h.

Figure 11. TGA curve showing the wt % of the 602020 vol %


NaClPLAPVOH composite blend as a function of temperature. At
the higher temperatures, the NaCl is the only remaining component
of the composite blend.
Journal of Biomedical Materials Research Part B: Applied Biomaterials

Figure 12. Graph showing the wt % NaCl remaining from the 60


2020 vol % NaClPLAPVOH composite blend after the TGA
experiments for different leaching times.

374

KRAMSCHUSTER AND TURNG

higher melting temperature than Celvol 502. SEM images of


the 602020 vol % NaClPLAPVOH composite blend
show what appears to be a fully leached part with pores
formed by leaching the salt particles and the PVOH (cf.
Figure 7).
NaCl Content

Figure 13. Graph showing the percent porosity of the molded samples as a function of leaching time. The porosity reaches a plateau
of 75% after 18 h. The error bars represent 6 one standard
deviation.

that the dispersed phase (PVOH in this case) size scale


changes from millimeters to microns within a very short
period. In this case, the use of a granular PVOH (Celvol
502) means the initial size scale of the dispersed phase was
already on the order of hundreds of microns or smaller. It
can be assumed that during twin screw extrusion, the granular PVOH was intensively mixed, further size-reducing
the granules into the micron-sized channel diameters
observed in Figure 6. However, for cell and nutrient transport to occur and for excretion of waste, it is necessary for
the pores and interconnecting channels to be at least the
size of a cell in suspension, or 10 lm.50 While the high
surface area-to-volume ratio that results from small pores
and interconnecting channels may be preferred, median
pore sizes on the order of 32 lm have led to more osteoid
growth in scaffolds when compared to scaffolds with median pore sizes on the order of 16 lm.9 Future work in
order to coarsen the phases of the scaffolds prepared in this
study through annealing51 may be necessary in order to
allow for sufcient cell and nutrient transport as well as
the excretion of waste.
NaClPLAPVOH (602020 vol %). Based on the results
of the NaClPLA composite and the PLAPVOH blend, a
NaClPLAPVOH composite blend was compounded using
the twin screw extruder and injection molded. Batch processes utilizing polymer extraction,2729,52 a combination of
gas foaming and particulate leaching,5357 and the aforementioned scaffold manufacturing processes provided the baseline for this material composition and process. A different
PVOH (AquaSol 116) was used for these experiments than
what was used for the 67-33 PLAPVOH blend (Celvol
502). AquaSol 116 is supplied in pellet form designed for
extrusion and injection molding, and it possesses a slightly

Porosity. Equation (1) assumes that PLA, with a density


of 1.24 g/cm3, is the only remaining material in the porous
structure. However, this is not the case as evidenced in Figure 12 using TGA. For example, due to the extremely high
wt % NaCl in the 602020 samples that had not been
leached, using Eq. (1) results in a porosity of 234.89%.
This is clearly not the case. Therefore, qapp in Eq. (1) was
re-calculated to calculate the actual porosities of the
foamed structures.
From Figure 13, it is clear that a maximum porosity of
75% was achieved after leaching the samples for 18 h.
This trend corresponds well with the residual NaCl content
shown in Figure 12. However, according to the original
composition of the 602020 NaClPLAPVOH composite
blend, the porosity should be at least 80% considering that
the NaCl and PVOH should both be fully extracted. However, the presence of residual NaCl, the apparent loss of
NaCl during pelletizing, and the likelihood that the gravimetric feeders were not 100% accurate when compounding
the material, lends insight into this discrepancy. If the
NaCl and PVOH contents had been 60% and 20% by volume, respectively, and had been fully extracted, the porosity of the samples would have been greater than 80% due
to the water-soluble materials and the presence of CO2
foaming. Further exploration into using a lower viscosity
PVOH may lead to higher interconnectivity, resulting in
less residual NaCl content and higher porosity.

CONCLUSION
This work represents the rst time that injection molding
has been used to create highly porous interconnected polymer matrices without the use of organic solvents. Porosities
of more than 75% with high interconnectivity were
achieved. Further work to control and quantitatively measure the morphology, reduce the residual NaCl content, use
medical grade materials suitable for a cell line experiment,
and evaluate the mechanical properties of these structures
will provide more insight into the feasibility of using injection molding to mass produce biodegradable tissue engineering scaffolds.
The authors would like to acknowledge the USDA Forest
Products Laboratory for use of their twin screw extruder and
TGA, Celanese Chemical Co. and A. Schulman for donating the
polyvinyl alcohol, Trexel, Inc. for the donation of a special injection molding screw, and Alex Chandra and Brian Ralston for
assisting in the experiments.
Journal of Biomedical Materials Research Part B: Applied Biomaterials

INJECTION MOLDING PROCESS FOR MANUFACTURING HIGHLY POROUS POLYMER MATRICES

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