Conference Session C1
Paper #6083
Disclaimer—This paper partially fulfills a writing requirement for first year (freshman) engineering students at the University
of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional, paper. This paper is based on publicly
available information and may not provide complete analyses of all relevant data. If this paper is used for any purpose other
than these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering students at the University
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USING ELECTROSPUN NANOFIBROUS TISSUE SCAFFOLDS TO PROMOTE
IN VITRO NEUROREGENERATION IN THREE DIMENSIONS
Mark Littlefield (mdl58@pitt.edu, Mahboobin 4:00), Ethan Paules (emp87@pitt.edu, Vidic 2:00)
Abstract – Electrospun nanofibrous tissue scaffolds are
currently being used for cell and tissue growth
in medical research laboratories and have proven to be an
effective
way
of
influencing
three-dimensional
neurogeneration in damaged brain tissue. Neural tissue
engineers have hypothesized that the technology’s promising
ability to accelerate tissue regeneration by promoting in vitro
three-dimensional nerve growth may be useful in combatting
Parkinson’s disease and other neurodegenerative diseases.
By continuing the research and development
of electrospun nanofibrous tissue scaffolds and how their
ability to enhance three-dimensional cellular growth can be
used to influence neuroregeneration, neural tissue engineers
are progressing towards increasingly effective methods
of repairing brain tissue afflicted by neurodegeneration.
Further success in this field of study could have significantly
beneficial effects on improved treatment strategies for
patients suffering from Parkinson’s disease and/or brain
damage. These advancements would not only provide a
higher quality of life for the victims of Parkinson’s disease
and other neurological conditions, but would also provide
relief for the families and friends caring for them. This paper
will primarily focus on the in vitro nerve growth-promoting
factors of electrospun nanofibrous scaffolds, and how this
developing technology has shown consistent potential in
hindering – and possibly reversing – the detrimental effects
of neurodegeneration.
Key Words – electrospun nanofibrous tissue scaffolds,
nanofibers, in vitro nerve growth, neurodegenerative
diseases, neuroregeneration, tissue scaffolds, biomaterials,
Parkinson’s disease.
for granted. These include but are not limited to the ability to
speak, walk, and even recognize family members. To better
understand how society can find an effective way of
combatting this problem, one must first take a look at the big
picture. There are two general pathologies of neural tissue
damage: physical and neurodegenerative. The first refers to
damage caused by traumatic brain injury, while the latter
refers to damage progressing over time. Further classification
of neural damage can be either acute, where a singular event
causes the damage (i.e. stroke, brain trauma), or chronic,
where
the
damage
grows
progressively
worse
(neurodegenerative diseases). These diseases are typically
caused by the accumulation of insoluble filamentous
aggregates within neural tissue, which underlie early axonal
dysfunction and pathology. This accumulation can
unfortunately lead to potentially irreversible neural damage
[1].
Another cause of many neurodegenerative diseases is
overactive astrocytes producing excess stress proteins, such
as glial fibrillary acidic protein, which is detrimental to
neuron survival [2]. This can lead to cell death and the
formation of cavities and glial scarring in neural tissue [1].
Based on the nature of these conditions and how they are
classified within the scope of neural tissue damage, one can
see just how challenging it is to combat such diseases. Up
until the start of the twenty-first century, the common belief
amongst medical professionals was that unlike other types of
cells in the human body, neurons had no capacity to repair
themselves after they had been damaged. As the number of
victims affected by neurodegenerative diseases like
Parkinson’s disease continues to rise each year, it is clear that
society has a pressing need for innovation in the treatment of
neurodegeneration.
NEURAL TISSUE ENGINEERING
Combatting Disease Progression
Neurodegenerative Disease
Neurodegenerative diseases, such as Parkinson’s disease,
are fairly common in today’s aging society. The effects of
these diseases can not only take a physical toll on the patient
but also an emotional toll on the patient’s family and loved
ones. The degeneration of neural tissue can steal from its
victims most of the abilities that we as a society tend to take
University of Pittsburgh Swanson School of Engineering 1
2016-03-04
Current treatment options for neurodegeneration focus
primarily on stabilizing symptoms and slowing the
progression of the disease through pharmacological means
and the development of medications [1]. The number of
prescription drugs currently available for these purposes is in
the dozens. One such example is carbidopa-levodopa. This
combination of drugs works by increasing dopamine levels in
the brain. Over time, however, the body adapts to the
Mark Littlefield
Ethan Paules
increased dopamine levels, and the drugs’ effectiveness is
diminished. This treatment strategy fails to stop the onset of
the disease. In addition, patients experience a multitude of
side effects including headache, nausea, dizziness, memory
loss, anxiety, depression, and trouble sleeping. This implies
that not only do family members or loved ones with these
diseases suffer from their direct symptoms, but that their
prescribed medication may be causing new symptomatic
problems, all while only slowing the inevitable progression of
neurodegeneration. This is a glaring issue, and thus the
scientific community has recently been brainstorming more
viable strategies for combatting disease progression.
Bioengineers present a new strategy. Instead of trying to slow
the onset of the disease, they are working to repair the damage
and possibly even reverse the effects.
Fabrication and Electrospinning Process
In order to generate a scaffold structure constructed from
conductive nanofibers, a polymer-solvent solution must be
put through a process referred to as electrospinning. The
electrospinning process begins by creating a desired polymer
solution. The type of polymer used can vary as different
polymers have been found to have different desired effects on
cellular growth. Typically, the chosen polymer will have a
high viscosity to prevent fracturing during the electrospinning
process. Examples of polymers that have been used for
electrospinning include Chitosan, a natural polysaccharide
made from chitin, synthetic, biodegradable, and
biocompatible polymers such as poly-l-lactic acid, poly
glycolic
acid,
and
poly
ε-caprolactone,
or
polyhydroxyalkanote-type
polymers
like
poly
3hydroxybutyrate [1]. A syringe is filled with the polymer
solution, and a relatively high voltage is applied to the
syringe [1]. This voltage creates a strong electrostatic force
within the syringe, causing a jet of the charged polymer
solution to eject from the tip of the syringe. The jet leaves the
syringe in a sweeping motion, allowing the solvent to
evaporate and leave behind nanofibers that have been spun
into a nanofibrous mesh on a grounded collector in a
phenomenon referred to as the Taylor cone [1].
Aligned fibrous meshes can be achieved by varying the
collection method [1]. The most common methods involve
collecting on a high speed rotating drum or disk [1].
This electrospun nanofibrous mesh is then seeded with cells
and coated with a hydrogel to keep the cells alive. A hydrogel
is a gel-like substance that can retain large amounts of water
[4]. There are two classifications of hydrogels: chemical,
which involves covalent bonding in its structure, and
physical, where secondary bonding is involved [4]. The
hydrogel keeps the cells alive by facilitating nutrient and
oxygen flow during the implementation of the overall
scaffold. Examples of commonly used hydrogels include
xyloglucan, which is found in the cell wall of all vascular
plants, polyacrylamide, which is synthesized in a lab using
nitrogen and N’-methylenebisacrylamide subunits, and
Hyaluronan-methylcellulose, which is composed of
hyaluronan and methylcellulose polymers [4]. Once the
electrospun nanofibers have been manufactured and coated
with a hydrogel, they can be used as a scaffold in order to
improve tissue regeneration in afflicted areas.
Neuroregeneration
To reiterate, it had been the common belief amongst the
scientific community for years that neurons simply could not
regenerate or repair themselves after they had been
significantly damaged, either by brain trauma or
neurodegenerative disease. In recent years, however, medical
researchers have found that there is indeed a potential for
neuroregeneration and repair [3]. Albeit this potential may
prove difficult to access, their findings show that the primary
reason damaged neurons cannot repair is because of their
surrounding environment not being conducive to their growth
[3]. Neurodegenerative disease often results in cavities, glial
scarring, and inflammation causing a poor growth
environment [1].
Therefore, it is in the best interest of bioengineers to
provide neuroprotection to reduce inflammation and prevent
secondary cell death, provide appropriate growth factors, and
promote neurite regeneration and growth to restore original
neural structure [1]. Currently, neural tissue engineering
strategies are being actively sought for the latter. One such
strategy for promoting neuroregeneration and growth in order
to restore neuron function and structure is the use of
electrospun nanofibrous tissue scaffolds.
Electrospun nanofibrous scaffolds have shown significant
promise in inducing in vitro neuroregeneration in three
dimensions. Though there are several factors of this
technology that make such growth possible, some of the more
significant factors include but are not limited to the
conductivity/biocompatibility of the scaffold surface, the
nanoscopic scale of the fibers and subsequent surface
porosity, and the three-dimensional structure of the scaffold
itself. While many other scaffolding technologies include at
least one of these factors, electrospun nanofibrous scaffolds
in particular have proven to have an optimal balance between
each of these factors. There is an ever-increasing amount of
supporting research for the effectiveness of these scaffolds,
some of which that will be discussed later on in this paper.
Scaffold Biodegradability
One key factor that is equally as important as electrospun
nanofibrous scaffold fabrication is the disintegration
mechanics behind these biodegradable scaffolds. Once the
scaffold has served its purpose by inducing axonal regrowth
across a nerve lesion, the scaffold should ideally have the
ability to “remove” itself from the biological system in a way
that will not contaminate or damage the site of repair. For this
ELECTROSPUN SCAFFOLDS
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Ethan Paules
reason, electrospun nanofibrous scaffolds are typically
constructed from a material that will be biodegradable in the
body. Tissue engineers can construct these scaffolds out of a
variety of different materials in order to control the time frame
of disintegration.
As a general rule of thumb, polymer solutions used for the
construction of electrospun nanofibrous scaffolds are
typically synthetically, naturally, or biosynthetically formed
[5]. Most synthetic polyesters can be hydrolyzed in the body,
where the ester bonds in the polymers are broken and the
subsequent products formed can be absorbed into various
metabolic pathways, therefore reducing the risk of
contamination at the growth site and the surrounding tissue
[5]. Scaffolds formed from natural materials have consistently
shown to have the most difficulty inducing neuroregeneration
across nerve lesions, and are typically more expensive to
produce. Natural materials do, however, optimize the
biodegradable nature of electrospun nanofibrous scaffolds,
and have proven to restore sensory function in as little as 8
weeks [5]. Biosynthetic materials, as indicated by the name,
serve as an effective middle ground between synthetic and
natural polymer solutions. Scaffolds formed from these
materials have increased biocompatibility over synthetic
ones, and increased mechanical strength over natural ones [5].
In regards to electrospun nanofibrous scaffolds specifically,
biosynthetic materials are used to create biopolymers, which
can in turn be put through the electrospinning process to form
the scaffolds themselves [5]. For this reason, neural tissue
engineers have begun shifting away from using purely natural
and purely synthetic materials, and instead have begun to
focus on developing optimal biopolymer solutions for these
scaffolds.
thought of as a series of complex circuity. In order to repair a
“blown fuse,” if you will, the replacement fuse has to be
similar to the damaged one in order to restore proper function.
The surface of electrospun nanofibrous scaffolds also
holds a biocompatibility factor that assists in influencing
tissue growth. The conductive surface of these scaffolds is
effectively able to mimic the extra cellular matrix (i.e. the
surrounding fluid of cells that is responsible for carrying
signaling molecules throughout tissues) [3]. The extracellular
matrix serves as a means for cells to signal and communicate
with one another over certain distances within tissue, and also
manages other types of cellular interactions and processes.
Surfaces that are able to more accurately imitate the extra
cellular matrix create an improved conducive environment for
other types of cellular interactions [5]. Biocompatibility
primarily stems from the selected polymer solution that the
electrospun nanofibrous scaffold is initially fabricated from.
Some biocompatible synthetic polymers such as poly(glycolic
acid) (PGA) have been found to induce nerve growth as well
as improve the overall structural support of these scaffolds,
though some natural materials such have chitosan have also
been used effectively [5].
Porosity & Adhesion
Proper alignment of nanofibers in tissue scaffolding
technologies has shown to improve scaffold porosity, which
plays a crucial role in influencing three-dimensional nerve
growth [7]. Pores are formed between properly aligned
nanofibers in the overall scaffold structure. Porosity directly
effects a wide variety of factors concerning the structural
integrity of electrospun nanofibrous tissue scaffolds. Cells
can lodge themselves within these pores and carry out a
variety of cellular processes, including but not limited to
nutrient exchange and cell-signaling [7]. In this way, the pores
can allow the growing tissue to establish effective cellular
roots within the scaffold’s pores, not unlike how a common
tree may establish its roots in soil as it grows.
Researchers from the National University of Singapore
found that random fiber alignment generally yields larger
pore size, while purposefully aligned fibers can yield smaller
pore size [7]. On a surface level, a decreased pore size will
yield smoother fibers, and a smoother scaffold surface overall
[7]. This is primarily due to the fact that aligning the fibers in
a particular way effectively increases their compactness,
therefore leaving smaller and fewer pores on the scaffold
surface [7]. Another team of researchers from NUS found that
a pore size of 1-2 µm served as an optimal influence on cell
migration across the scaffold surface, as well as on proper
nutrient exchange and signaling between cells [7]. Pore size
has also shown to have a direct effect on controlling and
maintaining a proper rate of degradation in the electrospun
nanofibrous scaffolds [7]. Arranging the nanofibers in a
longitudinal manner within the scaffold has proven to
decrease pore size on the scaffolds surface, and effectively
promote cell proliferation rate as a result [7]. By increasing
IN VITRO GROWTH PROMOTING
FACTORS
Conductive-Biocompatible Surface
As afore mentioned, neuroregeneration can be very
difficult to induce as neurons are not known to
grow effectively after they have suffered significant
damage [3]. In the brain, electrospun nanofibrous scaffolds
have proven to be effective in guiding accurate axon
regeneration over nerve lesions in both the peripheral and
central nervous systems [1]. For this reason, it is imperative
that the nanofibrous scaffold surfaces be conductive so
they are able to promote cell signaling within brain tissue that
nonconductive scaffolding technologies have not been able to
accomplish. Again, this conductivity is achieved through the
electrospinning process. The electric field created by the
potential difference across the syringe needle creates a small
amount of excess charge on the polymer droplets as they leave
the syringe. The like charges between the droplets repel
creating a structure that mimics the neural network in the
brain [6]. At a very rudimentary level, the brain can be
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Ethan Paules
the rate of cell proliferation, electrospun nanofibrous
scaffolds are effectively able to improve cellular interaction
with the conductive surfaces of the scaffolds, as well as
increase the rate of neural tissue growth in that area [7]. With
this information, neural tissue engineers can use decreased
porosity
to
potentially
influence
longitudinal
neuroregeneration along the nanofibrous surfaces of
electrospun scaffolds.
that due to a lack of support structure were not able to extend
any neurites in the z-direction [2]. Lastly, three-dimensional
cell cultures have been reported to enhance the differentiation
of mouse neural stem cells, which show increased rates of
differentiation and improved neurite outgrowth when cultured
on aligned nanofibers. This connects the three-dimensional
design factor with porosity which was previously mentioned
[2]. Both benefit from the use of aligned nanofibers as
opposed to random. This overwhelming evidence in favor of
three-dimensional scaffold structures shows the importance
of this design for the overall goal of promoting
neuroregeneration. Further evidence for this technology’s
efficacy from trials in mice is detailed in the next section.
Nanoscopic Fiber Scale
The nanoscopic scale of the fibers in electrospun scaffolds
enhances the scaffold’s ability to mimic the extra cellular
matrix [3]. This is due to the increased level of surface contact
between the cells seeded on the scaffold and the scaffold itself
[5]. The basics of biology tell us that cells with a high surface
area to volume ratio have an improved ability to engage in
molecular exchange and cellular signaling over cells with a
low surface area to volume ratio. This principle explains why
there is an existing hierarchy of cells congregating into tissue,
in turn congregating into organs, in turn congregating into a
multicellular organism (based on mammalian form). Given
that multicellular organisms generally follow this hierarchy,
and unicellular organisms generally exist as one large cell, it
stands to reason that organisms composed of many small cells
have shown improved evolutionary progress over unicellular
organisms. By maximizing surface contact with seeded cells,
the nanoscopic scale of the electrospun scaffolding fibers
provides an optimal surface area to volume ratio, effectively
optimizing neuroregeneration across the scaffolding surface
[5].
PROGRESSION OF CLINICAL
APPLICATIONS
Combatting “Parkinson’s Disease” in Mice
A collaboration between the Florey Institute of
Neuroscience and Mental Health at the University of
Melbourne and the Research School of Engineering at the
Australian National University explored the effectiveness of
using electrospun nanofibrous tissue scaffolds for threedimensional in vitro nerve growth in a mouse model of
Parkinson’s disease.
In this experiment, conducted in 2015, a polymer solution
was prepared for electrospinning by dissolving poly-l-lactic
acid in 10mL of acetone and chloroform at a ratio of 1:3 with
1 mM Dodeoyltrimethyl-ammonium bromide [8]. A custom
built electrospinning device was used at a voltage of 22 kV
[8]. A flow rate of 1.0 mL/h, a working distance of 10 cm
from a 13 cm diameter spinning mandrel rotating at 2000rpm
was employed [8]. The collected scaffolds were dried in an
oven overnight at 30° C [8]. Aligned scaffolds were
embedded in cryo-mounting media, sectioned on a freezing
microtome into short fibers ranging from 2 to 10 µm in length,
and collected into deionized water [8]. The short fibers were
washed in deionized water, ultrasonicated, and centrifuged
five times [8]. Short fibers were aminolyzed in 0.5%
ethylenediamine in isopropanol for 15 min at 20° C [8]. A
sulfo-4-N-maleimidomethyl-cyclohexane-1-carboxylic acid
solution was covalently tethered to the scaffolds to promote
the glial derived neurotrophic factor which is a measure of
how well the scaffold mimics the identity of the previously
functional neuron group trying to be repaired [8]. A
xyloglucan hydrogel was used to provide a prolonged and
controllable, trophic environment to promote the integration
of grafted cells [8]. Poly-D-Lysine (PDL) was coupled to the
xyloglucan by covalently bonding 54 mg of the PDL with 58
mg of 4-azidonaline using 155 mg of N-3dimethylaminopropyl-N’-ehtylcarbodiimide hydrochloride
(EDAC) in 140 mL of deionized water in an ice bath for four
hours without light exposure [8]. The solution was dialyzed
in deionized water for 48 h and lyophilized [8]. 100 mg of this
Three-dimensional Scaffold Structure
In recent years, the awareness of the necessity to culture
primary neural cells in a three-dimensional culture
environment has rapidly gained attention by the scientific
community [2]. Numerous analyses have been conducted
surrounding this issue of three-dimensional versus two
dimensional scaffolding. The results have been almost
unanimous in favor of three-dimensional geometry for several
reasons. For instance, neurons have the ability to grow in all
three dimensions, a property lost in two dimensional cell
cultures due to the planar surface [2]. As previously
mentioned, one of the causes of neurodegenerative disease is
overactive astrocytes in the brain overproducing stress
proteins such as glial fibrillary acidic protein [2]. Astrocyte
hyperproliferation is a hallmark of two dimensional cell
culture environments [2]. Furthermore, cell proliferation on
three-dimensional fibers has proven to be significantly higher
than their two dimensional counterparts because the threedimensional architectures improve the arrangement of cells
which assists in cell proliferation [7].
Neurons grown in three-dimensional cell cultures are also
able to extend their neurites through the entire thickness of
nanofiber scaffolds, in contrast to two dimensional cultures
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Mark Littlefield
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is the derivative duty for researchers in light of patient’s
autonomy to provide them the information and absence of
coercion to make a free and prior decision for any research
project to be provided to them [9]. The fourth describes the
social dimension of the fundamental principle of human rights
by emphasizing the equality among all individuals by virtue
of the equivalence of their dignity and rights [9].
Beginning with the first principle, the human dignity and
rights of potential tissue scaffold patients must be respected
through the implication of the FDA and researchers in the
required systematic and detailed scientific and clinical
analysis of the scaffolds to ensure their safety and clinical
efficacy [9]. The medical research community and its
regulatory bodies including the FDA owe patients a
commitment to prioritizing their health over industries who
can capitalize at worst, or fail to adequately consider at best,
patients’ distress stemming from their disease states that can
drive them to seemingly quick medical solutions [9].
From this ethical starting point, the second principle of
benefit and harm highlights the medical research community
and regulatory agencies’ duty to make unbiased judgements
from the scientific and clinical analysis of the tissue scaffold
devices [9]. Due to the complex and ever-evolving nature of
medical treatment and devices’ developments, the knowledge
of tissue scaffold patients to make their own judgment on
benefits and harms is compromised if scientists fail in this
duty [9].
Researchers in response to the next principle of autonomy
and consent are therefore obligated to properly assess,
understand, and communicate in an unbiased and
nondirective way the potential benefits and harms of a
treatment option in order for a patient’s consent to be validly
given [9]. Patients must have their autonomy respected to
have open, free, and understandable discussions about tissue
scaffolds to determine if their consent should be given or not
[9].
Finally, the application of the fourth principle of justice
emphasizes the importance of ethical device development and
its application across social strata [9]. For instance, if a tissue
scaffold required several operative revisions, the medical care
costs for such repeated surgeries would be prohibitive and
thus only available to people of higher socioeconomic status
[9]. Smarter device design on the part of the researchers may
ensure a more equitable distribution of these devices [9].
In sum, being the world’s expert on tissue scaffolds does
not make one an expert in their development or use [9].
Collaboration is a necessary dimension of research to ensure
that patients do not bear the harmful consequences of poorly
tested technologies [9]. Such ethical partnership from the
beginning of technology development and ongoing through
its practice in medicine is thus an integral part of quality
improvement to ensure that evidence-based medicine
includes an ethical base as well [9].
photosensitive intermediate product was recovered and
reacted with 201 mg xyloglucan in 6 mL PBS under 100 W
365 nm UV light for 150 s at 5 cm from the source and the
product was lyophilized [8]. The scaffolds were then coated
with platinum at 20 mA for 1 min in order to be examined
using scanning electron microscopy [8]. All of the images
were taken under 3 kV and an aperture of 7.5 µm with a
working distance of approximately 3.5 mm [8].
Measurements of the elastic shear modulus were also
performed [8].
The results of the experiment showed that they had indeed
engineered a microporous three-dimensional structure with
aligned fiber orientation and an elastic shear modulus
matching that of the rodent brain [8]. The scaffolds also
promoted the survival, differentiation, and plasticity of
ventral midbrain neurons in vitro [8]. Implementation of the
scaffolds showed biocompatibility with no increase in
reactive astrocytes, microglia, or inflammation [8]. The
physical properties of the host environment were also
improved by the bioengineering scaffolds [8]. These results
clearly show that this could serve as a viable treatment option
for humans suffering from Parkinson’s and similar
neurodegenerative diseases. The challenge is moving to the
human trial phase. As with any experimental treatment, there
are hesitations. Conducting an ethical analysis could help in
gauging a technology’s readiness for this step.
Ethical Adversity & Implications
Within medicine, few fields are as rapidly growing in
technical complexity and ethical challenges as surgery, in
which advances in bioengineering daily push the boundaries
human possibility [9]. It is necessary to note the importance
of evidence-based medicine, particularly with the correlate
that limited evidence for a new innovation should bid
practitioners caution [9]. A case study conducted by
UNESCO Chair in Bioethics and Human Rights Alberto
Garcia and Bioethics professor at the Athenaeum Pontificium
Regina Apostolorum Dr. Dominique J. Monlezun will be the
basis of the ethical analysis of our technology. We will adhere
the four principles for optimal patient application established
by this article: human dignity and human rights, benefit and
harm, autonomy and consent, and justice [9].
The first principle provides a foundation for the remainder
by asserting the primacy of the individual’s interests and
welfare over the interests of the society or scientific
community [9]. The second describes how the
operationalization of the first entails seeking the preferred
balance between benefit and harm for the individual [9].
Similar to the Hippocratic Oath with its insistence to “do no
harm,” this principle asserts that the minimization of direct
and indirect benefits for the individual must be sought during
the advancement of scientific knowledge and its medical
practice [9]. The third consists of the related principles of
autonomy and consent that define that parameters necessary
for researchers’ right relationships with patients [9]. Consent
Current Advancements & Areas of Future Focus
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Mark Littlefield
Ethan Paules
As global society continues to increase both in number
and in age, it can only be expected that the number of patients
suffering from neurodegeneration will continue to rise. In this
way, the ever-increasing number of victims can ironically be
partially attributed to medical progress and discoveries made
up until the present. These neurological conditions can be
emotionally taxing on both the victims of neurodegeneration
as well as their families. The degradation of brain tissue can
leave victims without the ability to speak, walk, or even
recognize family members. Neurodegenerative disease is one
of the few remaining “mysteries” of medicine that has not yet
been solved. Further progress in the field of neural tissue
scaffolding with electrospun nanofibers, however, has put
researchers on the right track to finally discovering a solution
to this medical epidemic. Electrospun nanofibrous scaffolds,
in particular, have recently proven to be an effective
innovation for inducing neuroregeneration across nerve
lesions caused by neurodegeneration.
Currently, public opinion on this relatively new medical
technology has remained relatively stagnant, given that very
few people are even aware of its existence or implications.
Nevertheless, biomedical and neurological research has
begun shifting substantially toward neuroregenerative
techniques, such as the electrospinning of nanofibers into
tissue scaffolds. Applying these techniques to neural tissue
scaffolding has proven to be one of the greatest challenges
facing researchers in the field today. Nevertheless, there has
been tremendous progress in the field of neural tissue
engineering at the hands of technologies like electrospun
nanofibrous tissue scaffolds. At the current rate of progress
being made by neural tissue engineers in the field today,
electrospun nanofibrous scaffolds could soon be used to
combat the damaging effects of neurodegenerative diseases in
human subjects. The coming clinical trials of this technology
are what will truly prove whether it is a viable combative
technique against neurodegeneration or not, and would have
a permanent impact on treatment options of the future.
Nearly everyone encounters a victim of a
neurodegenerative disease at some point in their lives. More
often than not, people know the victim on a personal level and
have felt the pain of watching a loved one slip away from
them at an agonizingly slow rate. The victims themselves tend
to lose their self-worth, and often become embarrassed and
frustrated with themselves due to the inevitable loss of their
independence. Through the research and development of new
neuroregenerative technologies, such as electrospun
nanofibrous tissue scaffolds, these pains could be eradicated
from victims and their families by the mid-twenty-first
century.
The future of medicine lies in the field of tissue
engineering, where new innovations and solutions have
already had a direct impact on the overall quality of human
health. As newly innovative neuroregenerative technologies
like electrospun nanofibrous scaffolds continue to be
developed at an exponential rate, neural tissue engineers of
the future wield the potential to reverse the detrimental effects
of neurodegeneration, and eradicate this universally painful
medical epidemic entirely.
REFERENCES
[1]
Yee-Shuan,
L.,
&
Arinzeh,
T.
L.
(2011). Electrospun Nanofibrous Materials for Neural Tissue
Engineering. Polymers (20734360), 3(1), 413-426. DOI:
10.3390/polym3010413
[2] Puschmann Till B., de Pablo Yolanda, Zandén Carl, Liu
Johan, and Pekny Milos. Tissue Engineering Part C:
Methods.
May
2014,
20(6):
485-492.
DOI:10.1089/ten.tec.2013.0445.
[3] “Neural Tissue Engineering at Wayne State University”.
Wayne State Giving. (2012). (Video).
https://www.youtube.com/watch?v=RuEIVwzGDio&index=
4&list=PLgZEQwPF_NZOZi--Vm63i9yzRY_EwK55_
[4] Wang, T.Y., et al. (2012). “Biofunctionalisation of
polymeric scaffolds for neural tissue engineering”. SAGE
Publications
Ltd.
(Online
Article).
DOI:10.1177/0885328212443297. p.369-390
[5] Cao, Haoqing, et al. (2009). “The application of
nanofibrous scaffolds in neural tissue engineering.” Elsevier
B.V. (Online Article). DOI:10.1016/j.addr.2009.07.009.
p.1055-1064
[6] Binan, Loïc, et al. (2014). “Approaches for Neural Tissue
Regeneration.” Stem Cell Reviews & Reports. (Online
Article). DOI:10.1007/s12015-013-9474-z. p.44-59
[7] Subramanian, Anuradha, et al. (2011). “Fabrication of
Uniaxially aligned 3D electrospun scaffolds for neural
regeneration.” Institute of Physics Publishing. (Online
Article). DOI: 10.1088/1748-6041/6/2/025004. p.1-9
[8] Ting-Yi Wang, Kiara F. Bruggeman, Jessica A.
Kauhausen, Alexandra L. Rodriguez, David R. Nisbet, Clare
L. Parish, “Functionalized composite scaffolds improve the
engraftment of transplanted dopaminergic progenitors in a
mouse model of Parkinson's disease.” Biomaterials, Volume
74, January 2016, Pages 89-98, ISSN 0142-9612,
http://dx.doi.org/10.1016/j.biomaterials.2015.09.039.
[9] Garcia, A., & Monlezun, D. J. (2015). “Global
Convergence on the Bioethics of Surgical Implants.” Biomed
Research
International.
(Online
Article).
DOI:10.1155/2015/853125. p.1-4
ADDITIONAL SOURCES
Kim, M. S., & Kim, G. H. (2014). “Highly
porous
electrospun
3D
polycaprolactone/βTCP
biocomposites
for
tissue regeneration.” Materials Letters, 120246-250.
DOI:10.1016/j.matlet.2014.01.083.
Mi, S., Kong, B., Wu, Z., Sun, W., Xu, Y., & Su, X. (2015).
A novel electrospinning setup for the fabrication of thicknesscontrollable
3D
scaffolds
with
an
6
Mark Littlefield
Ethan Paules
ordered nanofibrous structure. Materials Letters, 160343346. DOI: 10.1016/j.matlet.2015.07.042.
Nesil, Tanseli, et al. (2011). “Culture of central nervous
system neurons on electrospun polymer fiber-covered
surfaces.” 10th International Workshop on Biomedical
Engineering, BioEng 2011. (Conference Article).
DOI:10.1109/IWBE.2011.6079057. p.1-4
ACKNOWLEDGEMNETS
Special thanks to Eleni Anastasiou and Courtney Luk
from the University of Pittsburgh Writing Center for aiding in
the early development and drafting of this paper. Also, thank
you to engineering chair Juan Ibarra and engineering co-chair
Ryan Thomas for serving as advisors during the writing
process.
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