injection molding process

An Injection Molding Process for Manufacturing Highly Porousand Interconnected Biodegradable Polymer Matrices for Useas 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 2009Published 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 materialcombination, supercritical fluid processing, and particulate leaching techniques to producehighly porous and interconnected structures that have the potential to act as scaffolds fortissue engineering applications. The foamed structures, molded with polylactide (PLA) andpolyvinyl alcohol (PVOH) with salt as the particulate, were processed without the aid oforganic solvents, which can be detrimental to tissue growth. The pore size in the scaffolds iscontrolled by salt particulates and interconnectivity is achieved by the co-continuous blendingmorphology of biodegradable PLA matrix with water-soluble PVOH. Carbon dioxide (CO2) atthe supercritical state is used to serve as a plasticizer, thereby imparting moldability of blendseven with an ultra high salt particulate content, and allows the use of low processingtemperatures, which are desirable for temperature-sensitive biodegradable polymers.Interconnected pores of 200 lm in diameter and porosities of 75% are reported anddiscussed. ' 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 92B: 366376, 2010

Keywords: microcellular injection molding; tissue engineering; scaffolds; porous; manu-facturing

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 sub-

strates 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 sev-

eral 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 com-

mon synthetic biodegradable polymers currently used as

scaffolding materials include polylactide (PLA) and polygly-

colide (PGA), as well as their copolymers, and polycaprolac-

tone (PCL).24 Myriads of new materialsincluding

tyrosine-derived polycarbonates and trimethylene carbonate-

based materialsare also being explored as alternative syn-

thetic 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 char-

acteristics: (1) a three-dimensional and highly porous struc-

ture with an interconnected pore network for cell growth

and ow transport of nutrients and metabolic waste; (2) be

biocompatible and bioresorbable with a controllable degra-

dation and resorption rate to match cell/tissue growth invitro and/or in vivo; (3) have suitable surface chemistry forcell 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

Highly porous scaffolds are required to allow for cells to

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

Correspondence to: L.-S. Turng (e-mail: [email protected])Contract grant sponsor: NSF; Contract grant number: DMI-0544729

' 2009 Wiley Periodicals, Inc.

366

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 meth-

ods (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 depend-

ent on the type of tissue.2 However, even for bone regener-

ation, 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, withmany studies stating that macropores in the range of 150 to

350 lm are ideal.2,12,13 Therefore, macropores on the orderof 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 fur-

ther metabolized through the tricarboxylic acid cycle and

excreted as carbon dioxide and water.15 The issue of bio-

compatibility 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 surround-

ing 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 composi-

tion (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 poly-

mers.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.

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 ini-

tial 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 condi-tions needed to support cell growth. Additionally, espe-

cially in load-bearing instances, scaffold mechanical

properties that exceed that of the surrounding bone may

lead to stress-shielding, a condition where the surround-

ing 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 bio-

degradable polymers have been developed and extensive

reviews detailing these methods are available.25,12,13 How-

ever, 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, mechani-

cal and chemical properties, growth factors, and nutrient

transport on the effects of tissue regeneration both in vitroand in vivo, they do not address the need for cost-effectivemanufacturing processes to meet patient needs. The ability

to mass produce highly porous, highly interconnected scaf-

folds with complex geometries is essential to provide off-

the-shelf availability.25

Plastic injection molding has long been used to cost-

effectively manufacture complex 3D parts. Mechanical pen-

cils, 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-

TABLE I. Mechanical Properties of Human Tissues

Tensile

Strength

(MPa)

Compressive

Strength

(MPa)

Youngs

Modulus

(MPa)

Cancellous bone 8 412 50100

Cortical bone 60160 130180 330 3 103

Cartilage 3.710.5 n/a 0.715.3

Ligament 1346 n/a 65541

Tendon 24112 n/a 1432310

Adapted from Refs. 2 and 24.

367INJECTION MOLDING PROCESS FOR MANUFACTURING HIGHLY POROUS POLYMER MATRICES

Journal of Biomedical Materials Research Part B: Applied Biomaterials

acteristics also make injection molding an ideal manufac-

turing process to create 3D scaffolds, as long as high po-

rosity (e.g., maximum porosities of 80% have been shown

to be desirable for orthopedic applications12,26) and inter-

connectivity can be imparted into the nished product.

Recently, researchers have been striving to develop meth-

ods by which these characteristics can be imparted into

complex 2D and 3D structures via extrusion2729 and injec-

tion molding,3034 respectively, which may have the poten-

tial 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 poros-

ity and interconnectivity,3033 or they involve the use of or-

ganic solvents,34 which may be harmful to cells. This

research aims to provide a novel method using microcellu-

lar injection molding (to be discussed below) for the pro-

duction 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.

MATERIALS AND EXPERIMENTS

Materials

Polylactide. Polylactide (PLA) was chosen as the biode-

gradable 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). Itsglass transition temperature is 70 to 758C and its meltingtemperature is 1678C.

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 (Celan-

ese 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 AquaSol116 is supplied in pellet form and is designed for extrusion

and injection molding applications, this material was used

for subsequent compounding and injection molding experi-

ments. AqualSol 116 has a specic gravity of 1.27, a melt-

ing temperature of 1848C, and a melt ow index around10 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 willnot melt at normal polymer processing conditions used for

this research (under 2008C). The NaCl used for theseexperiments was reagent grade, purchased from Fisher Sci-

entic 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 nitro-

gen in most polymers and allows for larger cell sizes and a

greater density reduction when used in the microcellular

injection molding process.43

Experiments

Salt Reduction and Sieving. The NaCl particles were

size reduced using a Wiley mill and a screen with 1 mm di-

ameter holes. Once the particles were size reduced, they were

sieved to a size range of 150 to 300 lm using sieve screensand a wet/dry sieve shaker (H-4328, Humboldt Mfg.).

Compounding. The PLA, PVOH, and NaCl were com-

pounded using a Davis Standard twin screw extruder with a

screw diameter of 25 mm and an L/D ratio of 36.25. Thematerials 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 wasused. Upon extrusion, the strands were cooled with com-

pressed air and pelletized. The formulations compounded

and analyzed in this article can be found in Table II.

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 single-

phase polymer-gas solution. To facilitate fast and homoge-

neous 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 injec-

tion, 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

368 KRAMSCHUSTER AND TURNG


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-ure-

thane. While this process can be used to impart porosity

into the molded part, the supercritical uid also lls the in-

terstitial 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 toremove any residual moisture. The materials were injection

molded with a maximum barrel temperature of 1858C anda 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 combi-

nation, and at least three specimens were tested and ana-

lyzed 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-

ervoir. The water exited the bottom of the reservoir and

cycled back through the pump. The water was changed ev-

ery 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 cryo-

genically 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 rampspeed 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 1qappqPLA

3100 1

where Vf is the void fraction or porosity of the sample,qapp is the apparent density of the porous scaffold, andqPLA is the known density of the matrix material (PLA 51.24 g/cm3).

RESULTS

Morphology

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-

TABLE II. Formulations Compounded in the Twin ScrewExtruder

Materials

Composition

(vol %)

Blend 1 NaClPLA 41/59

Blend 2 PLAPVOH 67/33

Blend 3 NaClPLAPVOH 60/20/20

Figure 2. Schematic of the setup used for leaching the injection-molded samples.

Figure 1. Schematic of the microcellular injection molding processwith characteristic morphology.



tact with the water during leaching and the center portion

of the sample has closed pores due to CO2 foaming associ-

ated 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 magni-

ed 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 dis-

solved leaving behind the pores due to the NaCl particles.

PLAPVOH (6733 vol %). Because of the lack of inter-

connectivity 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 pre-

viously, PLA and PVOH have been shown to be immisci-

ble, though their ability to form a co-continuous blend

needed to be determined for this research. PLA was com-

pounded 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 sec-

tion of an extruded strand. Porous channels ranging from 1

to 30 lm were formed throughout the entire cross sectionof 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 biodegrad-

able scaffold.

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

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

Figure 5. Thin walls of PLA separate three pores left by directleaching of the NaCl particles.

Figure 6. Channels on the outside surface allowed for the dissolu-tion of PVOH in the center of the part that did not come in directcontact with water when rst placed in the leaching reservoir.



NaClPLAPVOH (602020 vol %). Combining polyvi-

nyl alcohol and particulate leaching with microcellular

injection molding resulted in a porous and fully intercon-

nected 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 par-

ticles. Evidence of this occurring can be seen in Figure 8.

Several magnied images of pores left behind by NaCl par-

ticles are shown with smaller pores (less than 10 lm) thatwere 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 dis-

solution 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 7. Cross-section of the NaClPLAPVOH (602020 vol %)composite blend showing what appears to be a fully leached sur-

face with uniform porosity throughout the part.

Figure 8. SEM showing the pores left behind by NaCl particles and the smaller channel diameters left behind by the PVOH that provided theinterconnected network for leaching.



has been dissolved. This topic is quantitatively assessed in

the subsequent section.

NaCl Content

Blend Composition. Because of the different densities

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 %. Thisdeviation from the theoretical NaCl content can be attrib-

uted 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.

Residual NaCl Content. TGA was used to quantitatively

determine the residual NaCl content of the 602020

NaClPLAPVOH composite blend as a function of leach-

ing time (cf. Figure 12). After heating to 7008C, the onlyremaining 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 translatesto a vol % of 2.0% for a solid composite blend. How-ever, the samples analyzed were highly porous as evi-

denced 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 po-

rosity. 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

NaClPLA (4159 vol %). Previous research using the

solvent casting/particulate leaching (SC/PL) technique dis-

cussed 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 intercon-

nectivity in the NaClPLA samples was due to the salt par-

ticles 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.

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

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 improve-

ments (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 forthe majority of uncompatibilized polymer blends, regard-

less of processing conditions. Part of the reason for this is

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



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 componentof the composite blend.

Figure 12. Graph showing the wt % NaCl remaining from the 602020 vol % NaClPLAPVOH composite blend after the TGAexperiments for different leaching times.



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 gran-

ular PVOH was intensively mixed, further size-reducing

the granules into the micron-sized channel diameters

observed in Figure 6. However, for cell and nutrient trans-

port 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 highsurface 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 osteoidgrowth in scaffolds when compared to scaffolds with me-

dian pore sizes on the order of 16 lm.9 Future work inorder 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 proc-

esses utilizing polymer extraction,2729,52 a combination of

gas foaming and particulate leaching,5357 and the aforemen-

tioned scaffold manufacturing processes provided the base-

line 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

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

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 Fig-

ure 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) wasre-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. How-

ever, the presence of residual NaCl, the apparent loss of

NaCl during pelletizing, and the likelihood that the gravi-

metric 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 vol-

ume, respectively, and had been fully extracted, the poros-

ity of the samples would have been greater than 80% due

to the water-soluble materials and the presence of CO2foaming. 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 poly-

mer matrices without the use of organic solvents. Porosities

of more than 75% with high interconnectivity were

achieved. Further work to control and quantitatively mea-

sure 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 injec-

tion molding to mass produce biodegradable tissue engi-

neering scaffolds.

The authors would like to acknowledge the USDA ForestProducts Laboratory for use of their twin screw extruder andTGA, Celanese Chemical Co. and A. Schulman for donating thepolyvinyl alcohol, Trexel, Inc. for the donation of a special injec-tion molding screw, and Alex Chandra and Brian Ralston forassisting in the experiments.

Figure 13. Graph showing the percent porosity of the molded sam-ples as a function of leaching time. The porosity reaches a plateau

of 75% after 18 h. The error bars represent 6 one standarddeviation.



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