Session A3 Bioengineering Topics 3
Paper #2077
ENGINEERED MAMMALIAN EXTRACELLULAR MATRICES REGENERATE
HUMAN SKELETAL MUSCLE
Jaclyn LaRosa (jml140@pitt.edu), Christian Ranallo (car97@pitt.edu)
Abstract— A young marine’s leg muscle is significantly torn
by a mortar. In the past, this marine would have been lucky
to survive; however, this man might now be given the chance
to run again due to regenerative medicine. Bioengineers
have intensified regenerative medicine through manipulation
of extracellular matrices proteins in regeneration of skeletal
muscle.
Extracellular matrices (ECM) of mammalian proteins are
structured to foster cell growth and differentiation through
cell maturity. The unique protein combinations in
mammalian matrices are recognizable by the body’s immune
system, and mammalian ECM are now being engineered to
regenerate lost and damaged skeletal muscles from injuries
with new tissues in human patients. Previously assumed to
be impossible, this regrowth of skeletal muscle is now
realistic, as implanted extracellular matrices act as scaffolds
to trick the body to believe the proteins are its own.
Recognizing these protein combinations and their growth
factors, the body begins to structure cells on the scaffold as
bone, muscle, and other tissues needing replacement.
Due to the great benefits of this technology, knowledge
about this evolving process should be shared with those who
can support and utilize it. Therefore, the purpose of this
paper is to describe the mammalian extracellular matrix
existence and purpose, the cellular connection between
mammalian ECM and the ECM from the body, the proteins’
implantation procedure onto wounds, and patients’ positive
physical responses to this treatment. This paper will assess
the benefits of this technique in the field of regenerative
medicine, focusing on the social and economic aspects
involved with skeletal muscle regrowth. The advantages of
this treatment in comparison to past techniques, such as
prosthetics and amputations, will be examined. The ethical
issues surrounding skeletal muscle regeneration will also be
analyzed.
researchers in bioengineering have discovered a way to
make trauma victims’ lives, such as this soldier’s life,
normal again.
Extracellular matrices (ECM) are now being manipulated
through regenerative medicine to act as scaffolding to
regrow lost or damaged skin and muscle. The matrices are
chosen for their unique, natural proteins, structure and
functions, which allow them to be recognized by the body’s
immune system and heal human wounds [1]. The matrices
are taken from mammals, engineered in various manners to
make them functional for implantation, and placed directly
on patients’ immense wounds. Past trauma-victim treatments
options, such as amputation and prosthetics, are now being
replaced this with regenerative medicine technique. Due to
its cost efficiency and effectiveness, matrices scaffolding has
led to significant successful results in patients’ bodies, their
social lives, and the engineering world. The ethical issues
involved with using extracellular matrices in regenerative
medicine are numerous and diverse, so engineers must be
conscience that their work with the matrices leaves a
positive influence on society and the healthcare world.
Key Words— Amputation, Extracellular matrices,
Mammalian systems, Muscle tissue, Prosthetics, Protein,
Regenerative medicine, Scaffold, Skeletal muscles
Within mammalian bodies, extracellular matrices main role
is within connective tissues. Extracellular matrices exist
between basement membranes, which are protective barriers
that separate the matrices from other cells and capillaries, as
seen in Figure 1. The inside portion of the matrices is
comprised of fibroblasts and an interstitial matrix, composed
of proteins that act a stress buffers for the whole
extracellular matrix between cells. The protein matrix
between the cells consists of numerous components, such as
collagen,
fibronectin,
carbohydrate
polymers,
polysaccharides, sulfates, and other minor role proteins [2].
A key to understanding the structure of extracellular
matrices is that these components are produced by resident
NATURALLY OCCURRING EXTRACELLULAR
MATRICES
Extracellular matrices (ECM) are not only the key to the
function and structure of mammalian body cells, but they
have become a key solution to solving problems within
tissue engineering. The unique and complex parts of the
matrix provide it with the functions necessary to regrow
tissue cells and heal human wounds. By tricking the body
into accepting the ECM proteins as its own, engineers in
regenerative medicine are now able to utilize the healing
function of mammalian ECM in trauma victims.
Matrices in Mammals
A NEW TREATMENT FOR TRAUMA PATIENTS
A young marine, fighting overseas in Afghanistan on his
first tour of duty, has a mortar explode less than 50 feet from
his post. Shrapnel from the explosion slices through his
thigh, gashing huge wounds in his flesh and muscles. In the
past, if this young man survived such trauma, he would have
spent the rest of his life confined to a wheelchair, unable to
ever walk again. However, as advances in medicine and
engineering have continued to shape our modern world,
University of Pittsburgh
Swanson School of Engineering
April 14, 2012
1
Jaclyn LaRosa
Christian Ranallo
cells, secreted through the basement membranes, and
combined with the existing matrices. This process allows the
ECM to reproduce itself, as well as regrow old or damaged
cells surrounding it. The main roles of the ECM derive
directly from this production process and the components
conducting it.
new cells, their various components allow them to heal small
wounds easily and quickly. Collagen and fibronectin act as
markers, signaling where the wound is and providing
strength during the new cells’ remodeling [2]. When the
body is faced with a serious, traumatic injury, outside
healing assistance is often needed for the injured part of the
body to regain function. This is due to the fact that injured
ECM is often corrupted and becomes unresponsive to more
cells growth factor signals. Regenerative medicine is now
using extracellular matrices to ‘trick’ the body into healing
faster when the bodies out matrices cannot work fast enough
to heal the wound.
All cells contain genetic material (DNA), which is
composed of different nucleic acids, expressed in
combinations to make unique proteins codes. These protein
codes are what denote a cell’s function and structure, but all
combinations of proteins are created using the same nucleic
acids. For this reason, extracellular matrices from outside the
body, even from mammals, can be used on human wounds,
and the body’s immune system will not reject the matrices as
an invader or infection to the body. When the body reads the
codes of the ECM proteins placed on the wound, it is tricked
to believe the implanted matrices are its own healthy and
functional ECM. This allows the new, mammalian ECM to
act as a scaffold on which the body believes it should grow
new cells, including muscle, skin, bone and blood vessel
cells.
Even though the trauma is greater in the larger healing
processes, it takes proportionally the same amount of time to
complete healing with the addition of mammalian matrices
as it would for the body’s own ECM to heal a smaller
wound. The protein recognition and scaffolding process is
what allows the ECM to play such a major role in
regenerative medicine. Trauma victims with chronic wounds
have long suffered life-long disabilities because of their
disabled extracellular matrices that could no longer heal
wounds, in addition to the lack of ECM healing application
in science [2]. Now, through this complex yet efficient
process of manipulating outside ECM as scaffolding, these
types of patients can now lead normal lives.
FIGURE 1
ILLUSTRATION DEPICTING EXTRACELLULAR MATRIX COMPONENTS IN
COMPARISON TO CONNECTIVE TISSUE [3]
The functions of the components of the ECM are what
truly play a huge role in the growth of cells by the ECM.
Composing 90% of the ECM, collagen provides structural
support to the resident cells [1]. Collagens are triple, twisted
helixes, made of alpha peptides, which enable them to have
immense strength [1]. Large bundles of different types of
collagen then form various-functioning, mature tissues in the
ECM. Fibronectin is the next key component within the
ECM, for it connects the collagen fibers to cells and the
matrix walls, allowing the cells to move through the ECM
[1]. This allows the matrix skeleton to move easily,
especially to affected areas in order to heal wounds.
Fiberonectin also plays a key role in the regrowth of skeletal
muscle cells through their adhesion. Skeletal muscle
differentiates between transcription markers during its
regenerative period, so it prefers attaching to the binding
area sequences on fiberonectin in order to get the best
growth response [4]. Next, elastin is especially necessary in
ECM during the healing process, for it is useful for skin and
blood vessel’s proper function. Cross-linked protein strands
give elastin the ability to stretch when needed and return to
its original state
Controlling the growth of certain cells within the body,
the matrix also has the role of regulating intercellular
communication and mediating growth factor activation. The
most important role the extracellular matrices possess that
pertains to regenerative medicine is their ability to heal
wounds.
MAKING IT HAPPEN
In order for the young, injured marine to walk again, his
treatment option must be perfected, as any mistakes could
lead to additional pain and problems. The process of
regeneration of human skeletal muscle using mammalian
extracellular matrices (ECM) begins with deriving the ECM
from the tissues of laboratory mammals. Porcine and bovine
tissues are the two most common sources of usable ECM,
although human tissue can be used, as well, depending on
the circumstance. The ECM can be taken from a variety of
body tissues, including heart valves, blood vessels, skin,
nerves, skeletal muscle, tendons, ligaments, liver, and other
organs [5]. The origin of the ECM is solely dependent on its
purpose within the treatment; for example, skeletal muscle
Connection to Regenerative Medicine
When the body becomes wounded, the ECM components
respond in four different phases: hemostasis, inflammation,
proliferation, and remodeling, each directed by different
growth factors [2]. Because ECM control the production of
2
Jaclyn LaRosa
Christian Ranallo
ECM is used primarily in the regrowth of large muscle
tissues.
A third common preparation for ECM involves
dehydrating the ECM in sheets and turning the sheets into a
fine powder intended for injection. Powder form dehydrated
matrices are especially useful for minimally invasive
techniques, such as scaffolding needed in the urinary tract or
other similarly small areas [5]. A final method of preparation
for ECM is producing it in a liquid or gel-like form. The
liquid form often works better than the powder form during
insertion, as it is easier to deliver to a specific site than a
suspension of powder particles [5]. Figure 3 clearly
demonstrates the difference in consistency between the sheet
form and powder form of ECM, which are specific to their
individual roles. In the regeneration of skeletal muscle, the
most useful and commonly operated preparation of ECM is
when it is in sheet form.
TABLE I
Preparing the Matrices
After the ECM had been extracted from the mammal, the
next step in the procedure is the decellularization of the
mammalian ECM. This process takes places to ensure that
the ECM is totally sterile, as to avoid being rejected by the
body’s immune system and avoid any bacteria being added
into the body [5]. In this process, all of the remaining cell
membranes, including living components of tissues or
organs and any other non-sterile particles that may be
present, are cleansed from the ECM scaffold. The protein
shell of the ECM remaining for implantation is the only
component left then. Following decellularization, the
remaining tissue shell must be rehydrated in order to
maintain the original tissue architecture [5]. Rehydration
must occur in order to prevent the collagen fibers from
collapsing and the ECM molecules from bonding within the
tissues. The ECM may also need to be dehydrated depending
on what the method of usage will be during the actual
implantation procedure.
There are several specific ways that the extracellular
matrices can be prepared for their use in human muscle
regeneration. One of the most commonly used mechanisms
is the sheet form. Dehydrated ECM scaffolds are often
compiled into a thin sheet of coarse protein material,
anywhere from a few millimeters to nearly a foot in length if
necessary [5]. These sheets function perfectly to cover large
injuries, such as battle wounds or other large amounts of
damage to body muscle. Another common preparation for
the dehydrated extracellular matrices is vacuum pressing,
which prepares three dimensional models of scaffolds. These
three dimensional models are most often used for the
regrowth of organs, mainly tubular ones, such as the
esophagus or other organs within the gastro-intestinal
system, as shown in Figure 2 [5].
EVALUATION OF THE FOUR MAJOR PREPARATIONS OF
EXTRACELLULAR MATRICES AND THEIR IMPLANTATION LOCATIONS
ECM
Preparations
Dehydrated
Sheet
Major
Advantages
-Large surface area
-Can regrow large
amounts of muscle
3-D Vacuum
Pressed
Model
-Pressed to fit
needed space
-Used to mimic
organ size and
shape
-Minimally
invasive
-Large surface area
for small amount
-Easy insertion
-Delivers well to
specific site
Powdered
ECM
Liquid/
Gel Form
Locations of
Usage
-Large wounds
-Soft muscle
tissue
Ex: quadriceps
-Organ or valve
replacements
Ex: larynx or
esophagus
-Small exposed
surfaces
Ex: fingers or
toes
-Small,
condensed areas
Ex: urinary tract
Implanting the Matrices
The most common and traumatic injuries inflicted on human
skeletal muscles occur to soldiers, who are fighting to
defend their country. In fact, the majority of physical injuries
that are inflicted on our troops are wounds to soft muscle
tissue. These wounds are often extreme, either being losses
of large amounts of muscle, or deep lacerations into their
muscle tissue [4]. The only significantly beneficial method
to treat these two types of wounds is the use of extracellular
matrices to regrow the missing tissue. Therefore with these
large wounds, the most beneficial method of preparing the
ECM is in dehydrated sheet form, shown in Figure 3, in
order to cover the most surface area within the injured tissue.
The prepared ECM is either sewn onto the remaining tissue
using organic thread that naturally disintegrates into the
body with no harmful effects, or the matrix is inserted into
the body through an incision created in the skin using microtechnology [5].
FIGURE 2
VARIOUS THREE-DIMENSIONAL MODELS OF DEHYDRATED
EXTRACELLULAR MATRICES SCAFFOLDS. THEIR APPLICATION
LOCATIONS (FROM LEFT TO RIGHT): ESOPHAGUS, [6]
3
Jaclyn LaRosa
Christian Ranallo
ECM, eventually regenerating the lost muscle tissue.
Through this complex process and the variety of resulting
benefits, trauma patients are left with the hope that they will
efficiently heal and their lives will continue as normal.
BENEFITING FROM THE RESULTS
The magnificence of the process of implanting extracellular
matrices (ECM) as scaffolding on wounds does not stop with
the proteins’ integration into the body. The benefits from the
results of this procedure are what have truly brought it into
the forefront of regenerative medicine. Compared to past
treatment options for trauma victims, such as amputation and
prosthetics, ECM scaffolding has proved to be a more
effective and efficient process of healing. The physical
benefits lead to social benefits in patients’ lives as well, as
patients can integrate themselves back into society at a
quicker and smoother pace. Economically, ECM scaffolding
will make a huge positive influence not only in patients’
lives, but the healthcare and bioengineering worlds. Despite
the extensive advantages to using extracellular matrices in
regenerative medicine, there are also a few drawbacks to the
process, but these aspects have not slowed down the work or
use of ECM.
FIGURE 3
COMPARISON BETWEEN THE SHEET FORM AND THE POWDERED FORM
OF A DEHYDRATED ECM SCAFFOLDING PRODUCT. THE CHOSEN
PRODUCT DEPENDS ON ITS APPLICATION LOCATION ON THE BODY. [7]
Once the dehydrated matrices have been inserted onto the
wound site, the body’s natural reactions begin to take over.
Due to the richness of growth factors and the abundant bifunctional molecules such as fibronectin and collagen within
the ECM, many biological activities that were previously
lost in the destroyed tissue begin again within the wound site
[4]. Cell growth is once again stimulated, as well as
angiogenesis, cell proliferation, cell migration, and cell
differentiation [5]. These activities are the basis for new cell
life, and as the number of new cells increases, new living
tissue begins to appear. The new tissue that is regenerated in
the wound is produced so that the structures of the tissue
cells are exactly the same to that of the original tissue, prior
to the injury. This process occurs because the new matrices
act as a natural scaffold for the production of this new tissue
structure, for the proteins that remain in the dehydrated
ECM are natural building blocks on which the production of
new cells occurs [4]. Growth factors in the ECM continue to
stimulate cell growth until the tissue has been regenerated in
its pre-injury form and size, and then the body notifies the
cells to stop growing.
Another large problem that the extracellular matrices are
able to overcome due to their organic nature is the body’s
immune system. When a major wound occurs, such as a
large laceration or the loss of a digit such as a finger or toe,
the normal response for the human body is to trigger an
immediate death to all cells that are now in contact with the
outside world [8]. This self-sacrifice occurs in order to
prevent bacteria, viruses and other unwanted pests from
entering the body. The cells then die, effectively
quarantining off the injured area. While this does protect the
living cells nearby and the rest of the body, it takes away any
chance of the injured tissues ever regenerating to their
original, functioning structures.
When the ECM is added to the wound site, the body does
not reject it, as the proteins within the dehydrated matrices
are recognized to be similar to those of tissues cells within
the body. The protein codes of the ECM are so similar, that
the proteins within the body read the ECM as naked
proteins, lacking companion cells. Because the body
believes this information about the new cells, it begins to
produce new, fresh cells on the protein scaffolding of the
Physical Results
When an amputation occurs on a patient’s leg at the knee,
the skin of the patient is sewn shut to replicate a continuation
of leg’s skin. This process may enable a prosthetic leg to
attach to what is left of the patient’s leg, but the internal
effects of the patient’s leg are not as pleasant. Nerve and
bone pain and poor circulation often reoccur throughout the
lives of amputee patients. These negative effects are the
results of the dead-ended nerves and scar tissue that form
when a section of a major part of the leg, or any limb, is
suddenly removed [9]. Over 57% of amputee victims using
prosthetics limbs say they are not satisfied with their
prosthetics device, and that they are forced to deal with the
issue of reoccurring pain at the site of their amputation [10].
On the other hand, ECM scaffolding prevents this trauma
or pain from reoccurring in victim’s lives. As a patient heals
using ECM protein power on their wound, the implanted
extracellular matrices regrow cells to replace the exact cells
that were removed. This process beneficially includes
restoring the exact function and structure of the previous
cells in the new cells, preventing a lasting, internal trauma
inside the body. On average after 12 weeks of treatment,
92% of patients are fully or partially healed after the use of
ECM scaffolding treatment on major leg wounds [9]. Figure
4 demonstrates this exact healing and efficient replication of
muscle tissue and skin through the use of ECM scaffolding.
4
Jaclyn LaRosa
Christian Ranallo
past trauma [10]. This positive outlook then reinforces the
benefits of regenerative medicine, leading to economic
boosts in bioengineering’s status through funding.
Economic Advancements
Treatment price and funding are always an issue in the
healthcare world, especially for complex, yet necessary
procedures. In the long-run, ECM scaffolding would be a
much cheaper and efficient choice versus having an
amputation and purchasing prosthetic devices. Muscle
regeneration requires a one-time payment for the ECM
scaffolding procedure, and the patients usually require no
other medical treatment in their life once the wound is fully
healed by the ECM. Even though trauma patients must
usually apply this powder to their wounds at least once a day
for several months, the manufacturing cost of the powder is
minimal compared to the amputation charges [13].
Amputation costs include: the surgery costs of tens of
thousands of dollars, hundreds of dollars in pain medication,
and approximately a $10,000 payment every 4 years for a
new prosthetic limb [13]. This excessive total cost can place
tremendous and continuous financial strain on families with
amputee patients.
The potential decreased demand for prosthetics in the
healthcare world by preserving limbs with ECM scaffolding
is also an economical benefit of this treatment. A small
move in funding and energy from designing new prosthetic
devices to regenerative medicine research would open up the
opportunities for more extensive cellular disease research
and ECM scaffolding in the bioengineering field. Once the
process of extracting and using ECM has been further
researched, the cost of manufacturing the ECM protein
powder will also decrease. The more ECM research is
funded in the bioengineering field, the more efficiently and
effectively cellular research in other fields of engineering
will occur, as they will be able to base their research off
concepts in regenerative medicine. Although, the intense
research in bioengineering and other research fields does not
come without precise concern of the ethical issues involved
in science and society.
FIGURE 4
KNEE AND THIGH OF ARMY CAPTAIN HEALED AND REGROWN USING
ECM SCAFFOLDING [11]
A few drawbacks do occur from using extracellular
matrices to heal wounds; the first being the initial length of
time to heal the wound. Although amputation usually leads
to future pain at the sight of the old wound, it also results in
immediate closure of the wound. Using ECM powder to heal
trauma wounds can take a week or so before the initial
would is closed over. Also, there is potential for the body’s
immune system to respond to the new ECM with rejection
[12]. Due to the same nucleic acids composing the old ECM
proteins and new, implanted ECM proteins, the body’s
rejection response is rare. If this negative response did occur,
it would be caused by mutations in the DNA composing the
implanted proteins, which the body would then not
recognize as its own [12]. Despite these minor issues
involved with the use of ECM scaffolding, the physical
benefits surrounding ECM use outweigh the drawbacks,
especially as they lead to many social benefits in patients’
lives.
Social Benefits
Returning to a normal life is one of the main goals of
manipulating ECM as a healing method for trauma patients.
When a patient is seriously wounded, such as a soldier’s leg
being shredded by shrapnel, his world stops and everything
he was involved with comes to a halt. The trauma victim’s
now focuses his remaining energy into regaining his life,
hoping to return to the place and time it was before his
injury. Because the new ECM implanted in trauma victims
enables skin, bone and skeletal muscle to regrow with the
same structure and function that it previous had, patients can
regain mobility and operation in their injured limbs in only a
few months [9]. In relation to the immense trauma the
patients have endured, this short amount of healing time
allows patients the ability to continue their lives without
making alternative plans for their future. Also, the regrowth
of skin and muscle due to ECM scaffolding provides patients
with the feeling of social acceptance after their injury versus
amputees and patients with prosthetics, who are often seen
differently in social places. Therefore, the morale and future
outlooks often increase dramatically in a shorter period of
time for ECM scaffolding patients versus amputees and
prosthetic patients, who live with a daily reminder of their
ETHICAL CONNECTIONS
People often believe that bioengineering is the most ethically
controversial field of engineering, as it is the only field of
engineering that deals directly with the human body. The
National Society of Professional Engineers (NSPE) created
an ethical code that sets the standards for ethical behavior
for all engineers, and the work done surrounding
extracellular matrices (ECM) must follow this code, as well
[14]. The process of regenerating human skeletal muscle
through the usage of ECM certainly faces several ethical
issues, as it does involve several topics which are considered
to be controversial in the world of ethics. However, this
scaffolding technique is proven to be ethically sound, as it
5
Jaclyn LaRosa
Christian Ranallo
does not conflict with the moral standards of society or with
the NSPE code of ethics.
Animal Involvement
A final criticism that commonly follows areas of research is
the use of animals and their treatment in the research. Many
people believe the use of animals as test subjects for
research is immoral and even against the law. People for the
Ethical Treatment of Animals (PETA) and other animal
rights activist groups are always attempting to rile the public
to protest the use of animals in laboratory testing, yet the
truth is that these animals are often treated better than many
others, such as animals used in media fields [16]. The
animals that are used in this research are never forced to bear
large amounts of pain or undergo tests in cruel conditions as
animals used in other fields of research often are subjected
to. The swine, cattle, and other mammals whose parts are a
crucial to this procedure are normally bred for food and are
treated with less care than those bred for labs are. Therefore,
much of the mammal tissue used in the procedures comes
from the cadavers of animals killed for other purposes, such
as for food. This method is possible because the scaffolding
procedure only requires the ECM of the mammals, which
can be obtained from the leftover organs of mammals
cadavers [5]. Preventing the waste of life, this process is the
most beneficial way to recycle the leftovers of animals used
in the food industries.
In addition, there are no actual laws restricting the use of
certain animals in research. The Animal Welfare Act (AWA)
is designed to set standards for the use of animals in
research, yet it does have specifications covering all animals
[17]. These unprotected animals include: rats, mice, birds,
reptiles, amphibians, and livestock, such as swine and cattle
that contain the needed ECM [18]. Engineers do provide this
humane treatment to animals, though, because they know the
benefits and the intensity of the complex research they are
completing, and researchers do not want their valuable, hard
work to be turned away by society.
Defying Divine Powers?
One focal point in the ethical battle involving the use of
ECM in muscle tissue regeneration is the misguided belief
that the scaffolding procedure is attempting to achieve a
level of progress that humanity should not be able to reach.
As human beings, we are conceived naturally, and we
receive the parts and body structure necessary to survive,
without extras. Therefore, when a patient is in need of an
organ, the only source for a replacement would be from
another human through a transplant. With new
bioengineering technology, the growth and reformation of
organs has become a reality, and many people view this as
immoral, a threshold that we as human beings should not be
able to cross. However, this is not true, as researchers are not
creating life out of nothing, or unnatural material; they are
simply taking living organic material and culturing it into a
product that is needed to heal the patient.
In the regeneration of skeletal muscle using ECM, entire
organs are not being produced, and no new life is being
created out of nothing. The process simply involves
implanting organic material from other mammals into the
body to help the body regenerate muscle tissue that was
already in existence prior to the injury that the victim
endured. This procedure does not break any moral laws, and
it certainly cannot be viewed as unnaturally affecting life or
extending the medical powers of society beyond human
capacity. Those that find the replication of nature to be
unethical can simply look around, as our society has been
replicating nature for thousands of years now. The difference
now is that this replication technology has a scientific
purpose, as it is used to heal and save many lives.
Natural vs. Unnatural
Another ethical complaint that groups often fire against
many bioengineering processes is the involvement of
implanting material into the body that is not naturally found
existing there. Realistically, this argument has no factual
basis, as any sort of artificial organ, prosthetic limb, or
transplant is adding something to the body that is not
normally found on or inside the body. In fact, almost the
exact same extracellular matrices compared to the new
implanted ones are naturally found throughout the human
body, as ECM is a vital component of the every mammalian
body. In the treatments to regrow skeletal muscle, the only
difference between the implanted ECM and the natural ECM
found within the patient is the origin of the matrices [15].
The implanted matrices are constructed of the same
collagen, fibronectin, nucleic acid protein codes and other
crucial components as the human ECM [5]. Although they
come from different sources, the implanted mammalian
extracellular matrices are essentially the same as the ECM
found within the body of the patient.
EXTRACELLULAR MATRICES – THE FUTURE OF
REGENERATIVE MEDICINE
Extracellular matrices (ECM) are more than supportive,
connective tissue in mammalian bodies; they represent a
future of new, directed research and saved lives, especially
to engineers in regenerative medicine. The unique
composition of ECM, mainly including collagen,
fiberonectin and elastin, allow them to play the role of
provider, supporter and director of their neighboring cells’
function throughout the body. ECM healing function is truly
their most crucial purpose, specifically to trauma victims; for
they are used to directly heal wounds by regrowing cells the
body’s damaged ECM would not be able to create. Through
a complex, yet refined process, the ECM is engineered to be
directly applied to patients’ wounds, where the body
recognizes the protein codes of the new ECM and
incorporates its structure as part of the body.
6
Jaclyn LaRosa
Christian Ranallo
[10] Timothy R. Dillingham, Liliana E. Pezzin, Ellen J. MacKenzie,
Andrew R. Burgess. (2001, August). “Use and Satisfaction with Prosthetic
Devices Among Persons with Trauma-Related Amputations: A Long-Term
Outcome Study.” American Journal of Physical Medicine & Rehabilitation.
[Online]. Available: http://ovidsp.tx.ovid.com/?QS2=434f4e1a73d37e8ce55
[11] Brian Gardner. (2012) “Regenerative Medicine Makes Advances In
Pittsburgh.”
Target
Health
Global.
[Online].
Available:
http://blog.targethealth.com/?m=20100616
[12] Gerhard Feil, Lisa Daum, Bastian Amend, Sabine Maurer, Markus
Renninger, Martin Vaegler, Jörg Seibold, Arnulf Stenzl, Karl-Dietrich
Sievert. (2010, December 15). “From tissue engineering to regenerative
medicine in urology — The potential and the pitfalls.” Advanced Drug
Delivery Reviews Journal, Volume: 63, Issue 4–5. [Online]. Available:
http://www.sciencedirect.com/science/article/pii/S0169409X10002905
[13] (2011, May 19). “Prosthetic Legs.” SciPolicy: Online Science Journal.
[Online]. Available: http://www.scipolicy.net/prosthetic-legs/
[14] (2012). “NSPE Code of Ethics for Engineers.” National Society of
Professional
Engineers.
[Online].
Available:
http://www.nspe.org/Ethics/CodeofEthics/index.html
[15] Drew Kuraitis, Céline Giordano, Marc Ruel, Antonio Musarò, Erik J.
Suuronen. (2011, October 19). “Exploiting extracellular matrix-stem cell
interactions: A review of natural materials for therapeutic muscle
regeneration.” Elsevier Biomaterials Journal, Volume 33, Issue 2. [Online].
Available:
http://www.sciencedirect.com/science/article/pii/S0142961211011707
[16] (2012). “The Issues.” People for the Ethical Treatment of Animals.
[Online]. Available: http://www.peta.org/
[17] Richard L. Crawford. (2012, February). “Animal Welfare Act Quick
Reference Guides.” United States Department of Agriculture. [Online].
Available: http://www.nal.usda.gov/awic/pubs/Legislat/awabrief.shtml
[18] (2012, February). “Public Law 89-544 Act of August 24, 1966.”
United States Department of Agriculture. [Online]. Available:
http://awic.nal.usda.gov/public-law-89-544-act-august-24-1966
Benefits of this treatment option outweigh the benefits of
older procedures, such as amputation and prosthetic use, for
the use of ECM scaffolding is less painful, cheaper, quicker,
and more socially inclined when healing trauma wounds.
Many ethical issues are also present when working in
regenerative medicine, especially with ECM. Bioengineers
must be conscious to sensitive subject matter, such as
surpassing the boundaries of human ability, placing
unnatural material in the body, and treating animals
humanely, when designing this sophisticated medical
procedure.
The future of regenerative medicine, the field of
bioengineering, the healthcare world, society, and the lives
of many trauma victims are all directly affected by the
research surrounding the use of ECM as skeletal muscles
scaffolding. The research and knowledge of ECM provides
other branches of bioengineering with a new, cellular basis
for their research. This foundation will increase the rate of
creation of other medical procedures and the healthcare
world’s plans concerning promising fields of developments.
Extracellular matrices scaffolding is truly emerging as the
most beneficial way to heal trauma wounds; and this process
deserves a significant amount of attention as momentous
benefits for all part of society derive from its outstanding
results.
REFERENCES
[1] H. Lodish, A. Berk, S. Zipursky. (2000). “Noncollagen Components of
the Extracellular Matrix.” U.S. National Library of Medicine. [Online].
Available: http://www.ncbi.nlm.nih.gov/books/NBK21706/
[2] G. Davin Haraway. (2006). “The Extracellular Matrix in
Wound Healing.” HealthPoint. [Online]. Available: http://www.owm.com/files/docs/Healthpoint_July.pdf
[3] (2004). ”Extracellular Matrix.” eNotes Science. [Online]. Available:
http://www.enotes.com/topic/Extracellular_matrix.
[4] Edward K. Merritt, M.S., David W. Hammers, M.S., Matthew Tierney,
B.S., Laura J. Suggs, Ph.D., Thomas J. Walters, Ph.D., and Roger P. Farrar,
Ph.D. (2009, November 19). “Functional Assessment of Skeletal Muscle
Regeneration Utilizing Homologous Extracellular Matrix as Scaffolding.”
Mary Ann Liebert Publishers, Volume: 16 Issue 4. [Online]. Available:
http://online.liebertpub.com/doi/full/10.1089/ten.tea.2009.0226
[5] Stephen F. Badylak, Donald O. Freytes, Thomas W. Gilbert. (2008, June
23). “Extracellular matrix as a biological scaffold material: Structure and
function.” Acta Biomaterialia, Volume: 5, Issue 1. [Online]. Available:
http://www.sciencedirect.com/science/article/pii/S1742706108002821
[6] Adam Piore. (2011, September 26). “How Pig Guts Became the Next
Bright Hope for Regenerating Human Limbs.” Discover Magazine: Health
&
Medicine
/
Biotechnology.
[Online].
Available:
http://discovermagazine.com/2011/jul-aug/13-how-pig-guts-became-hoperegenerating-human-limbs/article_view?b_start:int=1&-C
[7] Aaron Saenz. (2012, September 12). Singularity Hub. “Miraculous
Fingertip Regrowing Powder Strikes Again!” [Online]. Available:
http://singularityhub.com/2010/09/12/miraculous-fingertip-regrowingpowder-strikes-again-video/
[8] (2004). “Wound Healing and the Foreign Body Reaction.” University of
Washington: Engineered Biomaterials Tutorial. [Online]. Available:
http://www.uweb.engr.washington.edu/research/tutorials/woundhealing.htm
l
[9] Jonathon Moore. (2011, December 18). “The Healing Touch.”
Australian Trade Commission: Science Reaserch. [Online]. Available:
http://www.australiaunlimited.com/science/healing-touch
ADDITIONAL RESOURCES
D. Lucaciu, A. Todor, G. Baciut, M. Baciut, R. Campeanu, O. Lucaciu. 10
December 2010. “Regenerative Medicine versus Conventional
Auto/Allografts in Bone Reconstruction as an Option for Enhanced Quality
of
Life.”
IEEE
X-plore
Digital
Journal.
http://ieeexplore.ieee.org/?arnumber=5663602; Accessed: 27 January 2012.
Edward K. Merritt, Megan V. Cannon, David W. Hammers, Long N. Le,
Rohit Gokhale, Apurva Sarathy, Tae J. Song, Matthew T. Tierney, Laura J.
Suggs, Thomas J. Walters, and Roger P. Farrar. “Repair of Traumatic
Skeletal Muscle Injury with Bone-Marrow-Derived Mesenchymal Stem
Cells Seeded on Extracellular Matrix.” Mary Ann Liebert Publishers,
Volume:
16
Issue
9.
Available:
http://online.liebertpub.com/doi/abs/10.1089/ten.tea.2009.0826; Accessed:
26 January 2012.
Jolene E. Valentine, Neill J. Turner, Thomas W. Gilbert, Stephen F.
Badylak. 24 January 2012. ”Functional skeletal muscle formation with a
biologic scaffold.” Elsevier Biomaterials Journal, Volume 31, Issue 29.
http://www.sciencedirect.com/science/article/pii/S0142961210008021;
Accessed: 24 January 2012.
M. H. Derksen, K. Horstman. “Engineering flesh: towards an ethics of lived
integrity.” US National Library of Medicine.
Available:
http://www.ncbi.nlm.nih.gov/pubmed/18247157; Accessed: 26 January
2012.
ACKNOWLEDGMENTS
First, we would like to thank Piaget Francois, our section cochair, for meeting with us and constructively critiquing our
paper and future ideas. She helped us focus our research on
the right aspects and important concepts to engineers. Also,
we would like to thank Keely Bowers for her her time and
7
Jaclyn LaRosa
Christian Ranallo
advice concerning grammer as she graded our papers.
Finally, we would like to thank the Benedum Hall
Engineering Computer Lab for providing a quiet and
consistent place for us to meet and write our paper.
8