Session A1
201
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PLLA: A POLYMER AND A SCAFFOLDING MATERIAL
Navdeep Handa, [email protected], Mahboobin 10:00, Abigail Heron, [email protected], Budny 10:00
Abstract— Synthetic biodegradable polymers are valuable
in bone tissue engineering. Specifically, they serve as
scaffolds upon which cells of new tissue grow; however,
since they are biodegradable, they eventually fully
disintegrate, replaced by new tissue that they “signaled” to
grow. This degradability reduces complications associated
with traditional reconstruction methods, which often involve
metal implants that must be later surgically removed and
pose problems for MRIs. Additionally, the fact that these
polymers are synthetic allows for tailored engineering of
such factors as biodegradability and processability. One
such polymer, poly(L-lactic acid), also known as PLLA, is
highly significant in medical technologies because of its
superior mechanical properties, such as its optimal
degradation rate and renewability. The PLLA scaffold can
be made multiple ways, but one of the more adaptable
techniques is Thermally Induced Phase Separation (TIPS),
which maximizes control over porosity while not
compromising strength. Even with all its benefits, we must
note that PLLA scaffolding is a relatively new technology
and will be more expensive and thus prohibitive to lower
income groups until it is further developed. Almost a million
people per year are hospitalized by fractures that often
require extensive surgery. Thus, it is crucial that we further
study PLLA; with it, we may eventually phase out nonbiodegradable materials in bone tissue engineering. A
refinement and commercialization of PLLA scaffolding
would mean an easier healing experience for a substantial
amount of people.
Key Words—PLLA, Scaffolding, Bone Tissue Engineering,
Biodegradability, Phase Separation
PLLA: A POLYMER FOR FUTURE
INNOVATION
Polymeric materials, known commonly as plastics, are
ubiquitous in society: they compose a vast variety of
consumer products and are widely used as infrastructure
University of Pittsburgh Swanson School of Engineering
2.10.2017
components. Suzie, the average consumer, encounters
polymers everywhere from in the casing of her iPhone to the
Starbucks cup she slowly sips her coffee out of to the house
she sits in.
However, luckily for Suzie, the application of polymers
is not only limited to these sectors of society. With new
research and innovation constantly occurring, polymeric
materials are being used increasingly often in biomedical
applications, which focus particularly on coronary,
musculoskeletal, and dental applications among others.
Polymers have been used in biomedical applications since
the 1960s, but according to a comprehensive book on the
topic, Bioresorbable Polymers for Biomedical Applications,
they have recently come to play “a protagonist role in
medical science today” [1]. Since almost a million people
per year are hospitalized by bone breaks or fractures that are
so severe that they often require regeneration of the bone
altogether, this paper will consider bone tissue engineering
in particular [2]. Here, polymers are used as materials to
build scaffolds where tissue regeneration occurs. This
scaffolding method is more efficient, simpler, and more
effective in repair of severe bone fractures (those that cannot
be healed by a setting method involving a cast) than
traditional methods such as bone grafts: since these
polymers have chemical composition that makes them
biodegradable, they will absorb into the body naturally after
repair, as opposed to traditional material, such as the metal
used in bone grafts, that stays in the body.
PLLA, or poly(L-lactic acid), is one such polymer, and
although it is not necessarily a new polymer, it has an
optimal combination of the properties relevant to biomedical
application, most notably when blended somewhat with
other polymers. [1]. In order to truly optimize the application
of PLLA, one must understand the exact, detailed process by
which it is made and polymerized, and so this paper will
spend a significant amount of time on just that. It is the hope
of scientists and researchers that one day, when people like
Suzie break their bones, they can turn to polymers like
PLLA to provide a more natural healing experience. This
paper aims to further investigate the history, properties,
Navdeep Handa
Abigail Heron
production and application of PLLA.
bone tissue engineering and have been researched
extensively as scaffolding materials to regenerate new tissue
because they have very optimal properties for this purpose.
Polymers are biodegradable in the body and are thus said to
be bioresorbable. Bioresorbable materials degrade over time
as the bone regrowth progresses. These materials are made
up of non-toxic and/or natural materials that are either
absorbed by the body or eliminated by the metabolism [7].
Polymers used in scaffolding should be able to chemically
degrade in one of two ways. Hydrolytic degradation, as the
name implies, is prompted simply by water. Enzymatic
degradation involves many more biological agents and is
usually prompted by enzymes that are present during bone
regeneration [7]. The rate of degradation of the polymer also
plays a major role in a high-quality scaffolding. This rate is
determined by many factors, including crystallinity of the
polymer, the configuration of the structure, and the site of
implantation. However, the compatibility of a given polymer
within the body is largely based on the degradability and
biocompatibility of the structure.
PLLA is extensively used in the biomedical field due to
its
favorable
properties,
namely
bioresorbability/biodegradability and renewability. It
releases lactic acid as it decomposes; because lactic acid is
already found naturally in the body, it easily is absorbed in
the bloodstream or exits the body through the metabolism.
Carboxylic acid monomers are also released during the
degradation and aid in the reduction of the pH. Carboxylic
acid also acts as an auto-catalyst, as when it is produced it
aids in inducing further degradation. PLLA has a complete
absorption rate of around 2 years [8]. This rate is rather slow
for the healing of a severe bone injury, as even the most
severe of those take at maximum a year to heal [9].
However, PLLA (or PLA for that matter) is rarely used in its
pure, unadulterated form in its various applications. There is
a vast body of research that suggests numerous ways of
combining PLLA with portions of PLA, PDLA, or other
polymers entirely to optimize its material properties. Thus,
when PLLA is blended with other polymers, it often disrupts
crystallinity and accelerates the degradation rate drastically
[8].
PLLA AS A POLYMER
The concept of a polymer is fundamental for
understanding the structure of the tools humans use to
enhance their lives. A substantial amount of the objects one
uses every day are made out of various polymer plastics.
Some specific, common examples are polystyrene in foam
cups and PVC (polyvinyl chloride), which is ubiquitous
among piping systems. As explained by the American
Chemistry Council, a polymer is merely composed of one
molecule, aptly named a monomer, repeated several times in
an iterated, orderly fashion. Polymers are typically denoted
by a poly prefix with the monomer in parentheses directly
following, e.g. poly(glycolic acid) [3]. As a result of their
increased molecular weight and the bonding between the
various components, these large chains of monomers
together have properties that a single monomer could never
have alone. Typically, polymers are stronger, relatively
lightweight (at least compared to traditional building
materials such as metal, concrete, etc.), and generally more
malleable than metals, the traditional material used in bone
grafts [3].
PLLA itself is a polymer that is closely related to PLA,
poly(lactic acid), which was first successfully synthesized by
Théophile-Jules Pelouze in 1845; PLLA was only
successfully polymerized much later, in the mid-1990s [4].
PLLA and PLA are both derived from the monomer lactic
acid (known formally as 2-hydroxypropanoic acid,
CH3CH(OH)CO2H). Specifically, PLLA is a stereoisomer of
PLA. Stereoisomers are molecules that are structurally and
atomically the same, but differ in their orientation within 3D
space. The alternate orientations are labeled with letters
before the name of the monomer, such as “l” in the case of
poly(l-lactic acid) [5]. “L” specifically is one of two
denotations relating to a property of polymers called optical
activity, which is the direction in which they rotate light
polarized by a plane. “L” stereoisomers rotate the light in a
negative direction, while “d” stereoisomers rotate it in a
positive direction. A sample containing equivalent portions
of the two is called racemic and exhibits no optical activity
[6]. In the grand scheme of things, polymers differing along
this property (for our purposes, we consider PLA, PLLA,
and PDLA as concrete examples) are not fundamentally
different, and so the distinction seems incredibly minute.
However, it causes the physical properties of the molecules
in question to differ in a significant enough way for
consideration. For example, pure PLLA and pure PDLA are
both incredibly crystalline (hard/brittle), while PLA is nearly
amorphous (freeform/soft). This fact is exploited to develop
technology that is just the right mixture of crystalline and
amorphous by altering the ratio of PLLA to PLA (or PDLA
to PLA) [4].
Polymers, with PLLA being one notable example, are
increasingly becoming a crucial aspect to the research of
PRODUCTION OF PLLA POLYMER
The journey from the lactic acid monomer to a PLLA
scaffold ready for insertion into the body has been
extensively researched, reiterated, and refined, yet even to
this day, it is not an exact science (specifically with respect
to the creation of the PLLA scaffold). However, the science
is progressing at a remarkably rapid rate, and it is
converging to a standard procedure as the PLLA scaffold
moves toward being ready for industry.
The creation of the lactic acid monomer is a process
that has been utilized for thousands of years and in fact
occurs naturally in the human body: lactic acid fermentation
with bacteria. The specific bacteria that produce l-lactic acid
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are select bacteria of the Lactobacillus and Lactococcus
genera, including but not limited to Lactobacillus bulgarics,
Lactobacillus delbrueckii, and Lactococcus lactis [4]. In
order to prepare the sort of highly pure material needed for
polymer synthesis, this PLLA must be industrially
processed. A sample schematic for fermentation with
glucose is delineated in Figure 1 (most processes follow the
same basic structure) [10].
FIGURE 2 [12]
Types of polymerization
Direct polycondensation is the simplest method of
polymer creation from a monomer, and in fact, it was the
first method ever developed for polymerization. Indeed, it
was the method Pelouze utilized when he first synthesized
PLA [4]. Simply put, it is the connection of monomers
through condensation reactions to form polymer chains with
some byproduct, typically water. It is generally given by this
equation:
FIGURE 1 [10]
Lactic acid production schematic
Px + Py → Px+y + L {x}ϵ{1,2,... n} ; {y}ϵ{1,2,... n}.
Glucose solution enters the fermenter to be converted by the
bacteria into lactic acid in step 1; this mix is controlled for
temperature and pH by mixing with water and reacting with
calcium carbonate respectively. In steps 2-5, the biomass
waste is then separated from the calcium lactate (produced
by the reaction from the previous step), the calcium lactate is
reacted with sulfuric acid to form soluble lactic acid and a
calcium sulfate precipitate, and all resulting solids are
removed from this mixture. The resulting aqueous solution is
concentrated and purified in an evaporator and ion-exchange
columns in steps 6 and 7, respectively. It is then reacted with
an organic extractant solution to remove impurities,
converted back to aqueous solution, and washed with
sodium hydroxide and water, at which point a resulting
solution, now rich in lactic acid, has its light ends removed
and its heavy ends hydrolyzed in steps 8-14 [10].
The polymer PLLA itself is typically made through one
of three processes (typical to most polymers): direct
polycondensation, two steps polymerization, and ringopening polymerization (ROP), all three of which are
broadly
summarized
in
Figure
2.
Here, x and y stand for the number of monomers in a
polymer unit P, and L stands for a byproduct of low mass
[11]. Polycondensation is by far the most straightforward
and inexpensive method. However, it typically produces
PLLA of low quality and low molecular weight, mostly due
to the factor of L in the above equation: the byproduct
impurifies the resulting polymer [11]. Polycondensation can
be improved somewhat by expanding the mechanism to a
two-step process: the logically named two steps
polymerization which was mentioned earlier. Examples of
this type of process include azeotropic polycondensation
(AP) and solid state polymerization (SSP). The former
involves the removal of byproducts via an azeotropic
mixture (one with a constant boiling point though it is
composed of two different substances) and an equilibrium
manipulation to produce a polymer with a relatively high
molecular weight. The latter involves the production of an
oligomer (a molecule which is larger than a monomer but
still substantially smaller than a polymer) at high
temperature and subsequent combination with a prepolymer
(essentially, a polymer that has partially completed
formation and is now in a semi-crystalline powder-like
form) at a lower temperature [12].
However, the most well-researched, industrialized, and
generally accepted polymerization method is the ringopening polymerization (ROP) method; though it is more
expensive than direct polycondensation, the higher quality of
product justifies the increased cost. ROP does not involve
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Abigail Heron
the lactic acid monomer directly, but rather, as its name
implies, centers around the ring lactide, to which the lactic
acid is converted. The end of the lactic acid ring acts as a
reactive center onto which other monomers attach
themselves, and these are all in essence “opening” their rings
to create long polymer chains. Its industrial schematic is
given by Figure 3.
surpasses the technology in place now and is the next
breakthrough in the field of tissue engineering. Scaffolding
aims to eventually replace methods of bone repair such as
auto- or allo- bone grafts, which can heal many cases of
bone defect, including those caused by a breakage or chronic
infection [14]. For reference, a bone graft is a transplant of
bone tissue, either coming from an outside source (allograft)
or an inside source (autograft) that is held in place by metal
screws, pins, rods, etc. depending on the severity of the
injury [9]. Complications associated with the harvest of
autografts have compelled researchers to turn to scaffolding
as the answer. This novel technology is characterized by
typically good biocompatibility, biodegradability and
numerous similarities to a naturally grown human bone [14].
Bone tissue engineering is also incredibly versatile: it can be
applied to improve many clinical conditions, such as spinal
fusion, joint replacement, and severe fractures discussed
earlier [7]. Thus, bone tissue engineering has become a
major topic of research; many applications of this have been
examined in lab and clinical use.
A scaffold is an artificial and temporary extracellular
matrix that aims to regenerate missing tissues until they are
replaced by a newly synthesized natural extracellular matrix
[15]. An extracellular matrix is simply an outer layer
collection of cells that provide structural and chemical
support to the surrounding cells that do most of the regrowth
work. The replacement process that results in regrowth is
carried out by cells that attach to the scaffolding, fill the
pores within the scaffold material, and reproduce the
extracellular matrix, including the chemical functions it
should have as the artificial one degrades [15]. Thus,
effective scaffolds must have certain physical characteristics
to be advantageous for bone regeneration; among these are a
strong three-dimensional structure, evenly distributed
homogeneity, high porosity with and interconnected pore
structure, and a suitable surface structure for cell
proliferation [16].
The production of a scaffolding used in engineered
tissue starts with a design of the structure that considers
everything discussed above. Bone regeneration is a
multifaceted process, and the design of the scaffold needs to
reflect this. Osteoclast cells, bone cells that absorb bone
tissue during regrowth, are responsible for removing the
cells from the surface of the bone. The basic aim for a bone
scaffold is to imitate a natural bone regrowth as closely as
possible: that means supporting the cells that aid in this. This
structure must be able to support the migration and growth
of cells that will create the new tissue structure [17]. Like
the Pennsylvania Keystone, a scaffold must have an even
load bearing structure to allow for adequate cell growth and
function. The porosity and morphology of the material that
make up the scaffold also play an important role in the
quality of the tissue the scaffolding is capable of producing.
The interconnected pore structure plays a critical role in cell
seeding distribution, cell migration throughout the structure,
and perfusion of soluble signaling molecules, nutrients and
FIGURE 3 [13]
Ring-opening polymerization schematic
Lactic acid is fed into an oligomerization reactor, out of
which comes a steam that is mixed with some (typically
metal) catalyst and fed into a depolymerization reactor in
steps 1 and 2. From this reactor, a steam consisting of water,
lactic acid, and lactide are removed. The lactide and various
other impurities are condensed out in a drying column, and
any other contaminants are run through a purification
column in steps 3 and 4 [13]. The lactide that results from
this process is 99.9% pure, and it is this lactide that
undergoes melt-phase polymerization in steps 5-11. In this
process, molten lactide, a stabilizer, and a catalyst are
polymerized in a reactor; a devolatizer purifies the resulting
molten polymer of unreacted lactide, and deposits the
resulting PLLA as dried pellets [13]. Since this reaction is so
reliant on a large number of external variables aligning
correctly, such as temperature, catalyst, reagant, etc., much
time and energy has been spent optimizing the process. It is
generally accepted now that a stannous octoate catalyst with
a temperature of 150-210 degrees Celsius will yield a high
molecular weight; however, new methods are being
developed every day [12].
PLLA AS A SCAFFOLDING MATERIAL
Scaffolding, a method of bone tissue engineering, is
currently the most innovative and effective technique for
bone regeneration and tissue engineering. Current methods
have done a reasonably good job for decades; however, with
recent innovations in the medical field, scaffolding far
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metabolic waste removal [16]. Currently, there are many
techniques in the fabrication of porous polymeric scaffolding
in the field of bone tissue engineering. These techniques
include solid free-form fabrication, emulsion freeze-drying,
porogen leaching, fiber bonding, gas foaming and
microsphere sintering [8].
Logically, another key aspect to the creation of a good
scaffolding is having a polymer material that reflects all the
components that make up the scaffold. The chemical and
physical properties of the polymer that serves as the material
for the scaffolding determine the how effective the scaffold
is with regards to bone repair and proper bodily integration.
In fact, as of now, improvements in the field of bone tissue
engineering are primarily focused on the furthering of
research on synthetic polymers and their specific suitability
as an artificial scaffolding. The production of said polymers
is now a significant part of the future of medical bone
regeneration and tissue engineering. Specifically, this paper
will be focusing on poly(L-lactic acid) (PLLA). As
previously described, PLLA has many of the properties
crucial for an effective scaffolding, including its
biodegradability, specific similarities to natural bone
extracellular matrices, and a high porosity to aid in cell
distribution [17]. PLLA also has the very important quality
of being able to tailor its porosity and rate of degradation (by
combining in specific ratios with PLA and other polymers)
for optimal mechanical properties [17]. Thus, PLLA is a
very effective polymer for extensive use in bone tissue
scaffolding.
the solvent, it is forced into a liquid that forms a
homogeneous mixture with the original solvent. However,
the liquid cannot dissolve the polymer. Due to this reaction,
the solvent is removed from the polymer and the original
polymer precipitates as an array of fibers. [18]
In one experiment PLLA was blended with borosilicate
bioactive glass (BBG) to form a better structural support for
cellular attachment and proliferation. This experiment used
the wet spinning method. The PLLA-BBG fibers were
dissolved in chloroform solvent. This shows that PLLA can
be dissolved in chloroform. The solution was then extruded
via a syringe into a methanol bath. This caused the PLLABBG fibers to reprecipitate and form an array of pores [18].
The final method of production we will look at is
electrospinning. Similarly, as the aforementioned wet
spinning process a polymer is dissolved in a suitable solvent.
A high voltage system is connected to the end of a small
container of liquid solution. As the electric field intensity
increases the liquid at the top creates a cone like shape. Soon
the electric field causes the repulsive electrostatic force to
break the surface tension. The strand of polymer solution
undergoes a process of instability and lengthening where the
solvent evaporates. The fibers are then collected and the
resulting product is a fibrous layer of pores [19].
MARRYING THE POLYMER AND THE
SCAFFOLD: APPLICATIONS AND CASE
STUDIES
By and large, PLLA scaffolding as applied to bone
tissue engineering is still in its research stages. (PLLA as
used in other biomedical applications, such as blood vessel
reconstruction, has already seen patient trials [20].) The vast
majority of the research available right now is focused on
varying the method of production and tuning the blending of
PLLA with other polymers to produce an optimally
functional scaffold. However, there have been small but
significant steps toward patient trials: multiple (but different)
versions of a PLLA scaffold have been tested in rabbits with
positive results.
In 2009, F. Carfi Pavia, and his colleagues, V. La
Carrubba and V. Brucato in the Chemical Engineering
Department at the Universita di Palermo, conducted a
research experiment titled “Tuning of Biodegradation Rate
of PLLA Scaffolds via Blending with PLA” [21]. This
experiment tested blends of poly(L-lactic acid) and its
chemically and physically identical twin PLA in various
ratios as materials for scaffolds, which were produced in this
case via thermally induced phase separation (TIPS). The
ratios of PLLA/PLA tested include 100/0, 95/5, 90/10,
80/20, 70/30, and 60/40. These were created in two different
solution ratios of dioxane/water, 87/13 or 84.5/15.5.
Additionally, different polymer concentrations, 4% and 5%,
were tested [21]. The goal of the experiment was to
determine how the various blends of the polymers affected
PRODUCTION OF PLLA SCAFFOLD
A simple yet highly adaptive technique for creating
these scaffolds is thermally induced phase separation (TIPS).
Since its development in the 1980s, TIPS has been a popular
method of scaffold creation, especially because of its ability
to control degradation rate of the scaffold with minimal
external variable changes. The basic principle behind this
method is that as the temperature of a solution goes down,
the solvent’s ability to hold molecules in this solution
decreases; thus, a phase separation occurs when a solution
that is homogenous at high temperatures is cooled [17]. This
phase separation causes the polymer to split into a polymerrich phase and a polymer-lean phase. Once the solvent is
removed, a porous structure is obtained [17].
In the case of PLLA, the homogeneous solution is
often a combination of PLLA and another polymer that will
create a mixture of the desired properties. This process is
conducted in a solvent, primarily dioxane and water in the
case studies to be discussed next. However, PLLA
scaffolding can be created in many different solvent
solutions [17].
Another commonly used method to produce
scaffolding is called wet spinning. The process starts with
the polymer being dissolved in a suitable solvent, as in the
other two methods. Once the polymer is fully dissolved in
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Abigail Heron
the porosity and crystallinity of the scaffolding as observed
in various temperatures and dioxane/water ratios. On the
whole, the researchers discovered that as PLA content
increases, a higher dioxane/water ratio, lower demixing
temperature, and a higher polymer concentration must be
used to produce an optimally porous scaffold. The
temperature relation specifically is clear in Figure 4, which
shows a decreasing optimal demixing temperature for
increasing values of PLA content, and similar charts can be
inferred for the other two parameters [21].
being cooled slow to achieve big pores on the fast side and
small pores on the slow side. The results showed the slow
side having pores of about 70 micrometers in size and the
fast side having pores of about 240 micrometers in size.
Interestingly, the researchers also found that changing the
PLLA/HA ratio had no bearing on whether the scaffold was
effective; it simply changed the morphology of the scaffold,
and the addition of the HA noticeably improved the strength
[22].
While optimizing the production of PLLA scaffolding
is critically important, one must ensure that said scaffolding
functions well for in vitro applications. A related but
unassociated study in PLOS ONE (the Public Library of
Science’s journal) focuses on comparing the densities of
viable cells on scaffolds of three types of compositions:
PLLA/HA/Col, PLLA/HA, and PLLA/Col, where Col stands
for collagen 1, which is found in many tissues and organs. In
addition to measuring pertinent mechanical properties of the
scaffolds, the study analyzed the character (including
attachment, distribution, and protein localization, among
other things) of human mesenchymal stromal cells (hMSCs)
that differentiated on these scaffolds as a determinant of
scaffold success. The blend with all three biomaterials had
the highest density of viable cells and the highest
osteoconductivity, a measure related to the scaffold’s ability
to grow new cells, and had elevated levels of beneficial
minerals like calcium and osteocalcin [24].
As a final comment, the addition of naturally occurring
biomaterials such as HA and collagen are hugely important
to the viability of PLLA in biomedical application. Pavia
and others’ 2016 study, for example, clearly demonstrates
that since the PLLA/HA ratio does not affect the
effectiveness of the scaffold, scaffolds produced from these
materials could be easier to implement in large-scale
manufacture, since they do not depend on a greater variety
of factors aligning to produce a successful scaffold like
PLLA/PLA blends do. However, there is one caveat: the
more of these biomaterials are involved in a scaffold, the
more expensive it will be.
FIGURE 4 [21]
Demixing temperature needed for optimal porosity as a
function of increasing PLLA content
In 2016, these researchers joined forces with additional
researchers in their university to embark on a similar venture
with vastly different knowledge and results; this time, they
decided to use hydroxyapatite (HA) as the polymer to blend
with PLLA [22]. 58% of mammalian bone actually contains
HA, and so it certainly seems to be one of the best choices as
a biomaterial. However, it too is not an ideal scaffolding
material in isolation, as it is brittle and not as readily
available as PLLA [23]. Thus, a combination of the two is
the best compromise between authenticity of material and
production factors. The experimenters followed largely the
same basic experimental procedure with modifications to
reflect the refined scope of experimentation and some of the
newer knowledge and technology in scaffold development
that had become known in the past seven years. They only
tested PLLA with a polymer concentration of 4% this time,
and they also only tested two PLLA/HA ratios for the blends
[22]. The other novel part of this experiment is the creation
of scaffolds with a pore gradient. Pavia and the other
researchers learned from the results of their 2009 experiment
that the pore dimensions and character of the scaffold are
dependent on the thermal history (namely demixing
temperature). They now sought to expand upon this concept
and create PLLA/HA scaffolds with a gradient of pore size
varying along the thickness of the scaffold, as this gradient
more naturally mimics the human bone. They used a
technology called a Peltier cell to control both the
temperature and the cooling rate while creating the scaffolds
to achieve this, with one side being cooled fast and the other
ADVANTAGES, CONSIDERATIONS, AND
SUSTAINABILITY OF PLLA AS A
SCAFFOLD
Up until now, this paper has focused at length about the
use of PLLA as a scaffolding material in a technical sense,
with only brief consideration of its larger societal impacts.
This polymer must be sustainable if it is to be
commercialized and used extensively in the future of the
biomedical industry, and that sustainability must contain a
consideration of balance between minimal environmental
impact, biocompatibility, and optimal industry application.
PLLA is in a uniquely privileged position as a 100%
renewable polymer to be optimal for environmental
sustainability. Although most bio-based polymers are
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Abigail Heron
biodegradable, PLLA is one of the most sustainable for this
reason. In recent years, the average person has become more
and more conscious of their individual effect on the
environment; this is why more companies have been aiming
to make products out of sustainable materials, lowering their
carbon footprint. The use of chemically recycled PLLA is
undoubtedly part of the solution to the problems that plastic
disposal causes. When PLLA is depolymerized, the
monomers created can be used as a brand new raw material.
As an added benefit, this recycled PLLA is characterized by
the highest quality standards, which is incredibly useful in
creating high-quality recycled products that are worthy of
being sold [25].
However, the balance between biocompatibility and
optimal industry application is much more tenuous. In our
exploration of this, we will make mention of the vast
repository of other potential biomaterials for use in this field;
in doing so, we will accomplish the dual purpose of
providing a greater scientific context for PLLA and posit
where PLLA and its blends with other polymers lie on the
continuum between biocompatibility and industry
application. Poly(glycolic acid), more commonly known as
PGA, is a close cousin of PLLA and has incredibly high
strength and Young’s modulus (a quantity closely related to
rigidity); it has been considered for bone tissue applications
and is in fact currently used as a material in sutures.
However, it ultimately yields its authority in the bone tissue
engineering domain to PLLA. The product of its
degradability, glycolic acid, has the potential to cause tissue
damage, as degradation yields an overly localized
concentration of acid [8]. PLLA’s degradability product is
one that is already made naturally in the human body, lactic
acid, and thus it is a more preferable material in this regard;
however, there is still a risk of dangerous levels of acidity
occurring in degradation. In a different vein, one might
consider natural polymer materials such as hyaluronic acid,
agrose, etc., that are actually what the body is made of to be
the most superior of any scaffolding material. To some
extent, this is true; the biocompatibility is literally
unparalleled. However, their degradation rates differ within
the body because although enzymes are attuned naturally to
interact with these materials, enzymes differ from person to
person, and thus they cause drastically different reactions
among patients [8]. Moreover, they are hard to come by in
bulk, while lactic acid is the product of fermentation of
sugars that are ubiquitous in American markets. As can
clearly be seen, PLLA is the perfect combination of
biocompatible and relatively cheap and easy to manufacture.
However, it is not without its faults. With a slow degradation
time of approximately two years, it cannot be isolated if it is
to be used in bone tissue engineering applications; it must be
combined to some degree with another polymer to expedite
the degradation process to a sufficiently short timeline for
bone repair.
FOR PLLA
As we have discussed in this paper, polymeric
materials are everywhere. We all interact with them every
day, whether they are the pens we use to the containers we
store them in. With how important these polymers are for
everyday applications, it would make sense that we use them
in our bodies too, and thus newer research specifically
investigates the use of these polymers for biomedical
advancements.
PLLA’s renewability and biodegradability make it
highly attractive as a base for biomedical applications. It is
also able to be manufactured through various techniques.
With the expansive research in the field of tissue engineering
that has been going on for the past decade, the future looks
bright for biodegradable polymeric scaffoldings, especially
those containing PLLA. PLLA has all the needed
characteristics to be a prominent polymer in this field, as it is
biodegradable, highly porous, and capable of blending with
other polymers to form a perfect polymer for scaffolding.
Though this technology has a long way to go until it is ready
for industry, it is the hope that the vast benefits and virtues
of it will be realized once it is.
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ACKNOWLEDGMENTS
We would like to thank our writing instructor, Janet
Zellmann, for providing us with insightful and useful
comments on our written work, and always sending
incredibly nice emails. We would like to acknowledge our
co-chair, Mikayla Ferchaw, for providing comprehensive
feedback on our outline and providing us with resources
with which we can write this paper more effectively and
being someone we can reach out to. We would like to
acknowledge the 24-hour study space provided by the
Hillman Library, which has so graciously entertained the
laughs, cries, and stress resulting from the creation of this
opus while providing a source of caffeine to fuel it all. We
would lastly like to acknowledge this acknowledgements
section for affording us the opportunity to craft some vibrant
prose, which we often do not get the chance to do as
8
Navdeep Handa
Abigail Heron
engineers.
9