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Injection Molding Process
Injection Molding Process
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
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
366
Surface Chemistry
367
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
Mechanical Properties
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
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.
Experiments
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.
369
Blend 1
Blend 2
Blend 3
Materials
Composition
(vol %)
NaClPLA
PLAPVOH
NaClPLAPVOH
41/59
67/33
60/20/20
Figure 2. Schematic of the setup used for leaching the injectionmolded samples.
Vf
qapp
1
3100
qPLA
370
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.
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
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
DISCUSSION
Morphology
NaCl Content
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.
374
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.
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
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