The document describes a new artificial knee joint replacement called the Orthogenua Joint Replacement. It is designed to integrate permanently with the patient's bone using their own stem cells and biodegradable materials. This would allow for increased mobility and flexibility compared to current replacements, which often need to be replaced after 10-15 years as they wear down. The joint replacement will be tested in goats to evaluate bone integration and durability over time compared to a healthy joint. If successful, this permanent replacement could improve the lives of athletes and others by eliminating the need for multiple revision surgeries over a lifetime.

1. Introduction:
Our “scientists” are currently in the process of developing an artificial knee joint
which can be used instantly after surgery and will last a lifetime. We have approached
this challenge by combining the pros of both the cemented and uncemented knee joint
replacement techniques. We hope that our intensive research will bring forth a new era
to orthopedic surgery, improving the lives of many young and old athletes. By using
autologous stem cells and microsphere scaffolding we have developed the Orthogenua
Joint Replacement. The design of our product is to insure the permanency of the
artificial joint, for most artificial joints wear down with use over the years. The
Orthogenua Joint Replacement will allow for increased mobility, flexibility, and longer
lasting product.
Background Information:
The joints are considered part of the skeletal system. The skeleton is made up of
over two hundred bones; The twomain bones this study will focus on are the tibia and
the femur. Bones have several functions including: creation of new blood cells, mineral
storage, protection of vital organs, assisting with movement, and maintaining the
structure of the body (Class Powerpoints 2014). The joints play a major part in assisting
with movement. The muscles contract and pull on the bones, causing them to move. The
knee joint supports your entire body weight and is subject to constant and immense
stress.
Pathologies:

2. There are many reasons why someone may want or need an artificial knee joint
replacement. Some might be athletes who have suffered sports accidents or people
suffering from cartilage pathologies. Some examples of cartilage pathologies are
arthritis, which is the chronic inflammation of articular cartilage, and osteoarthritis,
which is when cartilage around the bone wears down over time. A total joint
replacement is the best treatment for both osteoarthritis and arthritis. Unfortunately
there are some cartilage pathologies that are incredibly hard to treat such as rheumatoid
arthritis. Rheumatoid arthritis is the chronic inflammation of all the connective tissue;
every joint. This disease affects the knees most. After time the joints become to get
distorted which can be very painful.
Current Technology:
In the world of an orthopedic surgeon there are many decisions that must be
made before, during and even after the surgery to ensure their patient recovers and
heals properly. One of the big decisions before surgery is whether to use a cemented
joint, an uncemented joint, or microfractures which are all current methods in treating
both osteoarthritis and arthritis. Cemented and uncemented joints have the same
function but are attached differently to the knee, resulting in differing recovery rates
and longevity.
Joints that are attached using bone cement are ready to use very soon after
surgery since the cement adheres quickly and efficiently; however, cemented joints wear
down in a span of 10-15 years and may need to be replaced at some point. Cemented
joints are usually put in more elderly patients because they do not want to take the time
to recover and since the joint is only going to be used for about 10-15 years. Even though
the recovery time for a cemented joint is rapid, the range of motion is limited because

3. the bone cement is rigid limiting the motion of the knee. This side effect is counter
productive because most who choose to have a cemented knee replacement are athletes
who want to recover quickly to get back into training.
In the non-cemented joints use a precisely textured rod that fits into a carved out
portion of the bone marrow in the themer and tibia. This texturing allows cells to grow
into the rods and secure it permanently. Although these joint replacements take a longer
period of time to heal they are permanent and erode with time. Due to the endurance of
this joint replacement, it is put in younger people such as teens or early adults. This
joint is used for younger patients since they can recover faster and so that they do not
have to return for future surgery.
The third method available to surgeons for treating cartilage pathologies is
microfractures. The process or creating microfractures creates tiny fractures in the
cartilage and bone of the knee. These fractures tap into the bone marrow which yields
stem cells which are released into the bone and cartilage. The stem cells form new bone
and new cartilage; however, the cartilage formed is weaker than the original and will
wear away faster than normal cartilage. The side effect may lead to multiple surgeries in
the future which costs time and money for the patient.

4. "Cemented and Uncemented Prosthetics." WebMD. WebMD, n.d. Web. 10 July 2014.
The Status Quo:
Diseases, like arthritis, or injuries can
damage knee joints. Knee joints are replaced with
a prosthetic joint that is held in place by bone
cement. Modern knee joint replacements are
perfect in most categories: They relieve pain and
most people don’t need any extra help after the
surgery. However, the modern method doesn’t
account for the fact that an artificial knee joint
can’t replace the full functionality and
biocompatibility of a knee joint made out of a patient’s own cells. They also don’t last a
lifetime. “An increasing number of younger people are also replacing their knees
because of injury from high-impact sports and activities that wear out their knees early”
(drugwatch.com 2014). The average knee joint replacement lasts about 10-15 years
(nih.gov 2011). If a teen receives a joint replacement they will have to have at least four
more surgeries during their lifetime, if they live to the U.S. average life expectancy. If a
professional sports player receives a joint replacement at any point in their career then
they would at least three more surgeries during their lifetime if the live to the U.S.
average life expectancy. Full recovery can take an additional three months and rehab is

5. Figure 1: X-ray (lateral
View) of Knee Joint
Replacement
Manhattan Orthopedic &
Sports Medicine Group
2012
Figure 2: X-ray (lateral View) of Knee
Joint Showing Posterior Dislocation
Villanueva – Indian Journal of
Orthopaedics 2010
sometimes necessary. In some cases, recovery can take a full year. Having to waste years
of one’s life recovering after multiple joint surgeries can be a grueling process.
In addition to time spent, the efficiency of the new joint may not always match
that of the replaced joint. Joint dislocation is possible. When joint dislocation occurs a
new surgery is necessary. This again aggregates to the fact that the current method of
joint repair can be a long and arduous process.
Anoth
er key
issue
with the current method of knee joint
repair is the cost. The average cost for one surgery is about $50,000
(huffingtonpost.com 2014). If you include the cost of recovery, rehabilitation, and
check-ups the numbers start piling up. Then you have to multiply that cost by the
numerous surgeries that are necessary because the joint repair only lasts 10-15 years.
Athletes, who may want joint repair faster so they don’t have to wait until the joint
wears out, will have to pay even more. What is even more startling about the cost of joint
replacements is that they cost more
than the average annual income in 18
U.S. states (huffingtonpost.com 2014).

6. In addition to cost, join replacements are becoming increasingly common. “More
than 1 million Americans have a hip or knee replaced each year” (niams.nih.gov 2012).
If a teen has a joint replacement surgery and has replacements across their lifetime, the
cost could spiral into the hundreds of thousands of dollars. Multiply that by the million
Americans who are getting replacements each year and you have a multi-hundred-
billion-dollar problem.
Materials and Methods:
Our product is an improvement on joint replacements, mainly in the knee. The
joint replacement will be made from Trabecular Metal and adhered to that metal using a
biodegradable and biocompatible gecko-inspired tissue adhesive is a highly porous layer
of microsphere scaffolding that is engineered to release the necessary growth factors.
Both the Trabecular Metal and microsphere scaffold will be seeded with mesenchymal
stem cells from the patient’s removed bone marrow. The joint replacement will be held
in place by biodegradable calcium sulfate bone cement. Eventually that bone cement will
disappear completely and the joint replacement will be held in place by the newly grown
osteocytes.
Trabecular Metal is made of tantalum, a highly biocompatible and corrosion
resistant material that causes little to no adverse biological response (Harling 2002)
(Zimmer 2013). “Many studies demonstrate [tantalum’s] excellent biocompatibility in a
variety of situations including, those applications involving bone surgery” (Robert J
Harling 2002). Trabecular Metal was developed and patented by Zimmer Dental. It has
many properties that mimic those of cancellous bone, including interconnected pores, a
maximum of 80% porosity, and a low modulus of elasticity similar to cancellous bone

7. Image From:
http://www.zimmerde
ntal.com/tm/osseoinc
orporation/osseoincor
poration.aspx:
(Zimmer 2013). It has also exhibited high ductility without mechanical failure in
compression testing (Zimmer 2013). Because of its interconnected porosity, Trabecular
Metal allows for cell ingrowth of osteocytes and fibroblasts that will eventually hold the
joint replacement in place. The Trabecular Metal can be shaped into any desirable
shape, including ball and socket joints, hinge joints, and more. Trabecular Metal is
manufactured by “utilizing a thermal deposition process, elemental tantalum is
deposited onto a substrate, creating a textured surface topography to build Trabecular
Metal Material, one atom at a time” (Zimmer 2013).
To affix the Trabecular Metal to the microsphere scaffold, a
biodegradable and biocompatible gecko-inspired tissue adhesive is
used. This adhesive is created using nano-patterned polymers and
was inspired by the adhering abilities of the feet of geckos (Kumar 2009). This adhesive
meets the requirements of biocompatibility and biodegradability, so as the osteocytes
and fibroblasts grow
into the joint
replacement the
adhesive will degrade
along with the
polymeric scaffold
with hydrogel porogens and eventually the newly formed bone will be all that is left. This
adhesive is made of polymeric, conical pillars developed using a silicon template. The

8. surfaces of the pillars are then nano-patterned to increase the adhesion to flat surfaces
almost two times more (Kumar 2009).
Using the adhesive described above, a layer of a biodegradable microsphere
scaffold is attached to the Trabecular Metal joint replacement. Microsphere scaffolds
can be engineered and adjusted to release drug or growth factors at any desired rate. In
this case the microsphere scaffold would be developed using polymers with a high
molecular weight, due to the polymer’s high density the growth factors would be
released at a slower rate (Dhandayuthapani et al 2011). Microsphere scaffolds have
interconnecting pores which will allow for the ingrowth of cells. The microsphere
scaffold is also biodegradable so they will disappear as the osteocytes and fibroblasts
grow into the region. These microsphere scaffolds are manufactured using a process
called solvent/non-solvent sintering (Laurencin et al 2011). Sintering is joining
polymeric microspheres, placing them in a mold of the desired shape and size of the
scaffold (Laurencin et al 2011). Then the solvent/non solvent liquid is poured into the
mold and that liquid is allowed to evaporate (Laurencin et al 2011). The proportion of
liquids and the diameters of the microspheres can then be adjusted (Laurencin et al
2011).
Mesenchymal stem cells are found in bone marrow and are multipotent; they
have the ability to differentiate into several different cell types, including bone and fat
cells (Nombela-Arrieta et al 2011). To insert the joint replacement the bone must be cut
and the bone marrow inside must be removed to make room for the replacement. Using
stem cells that are isolated from this leftover bone marrow has several benefits. The
stem cells don’t need to be taken from another part of the patient; the bone marrow is

9. "GEN | Insight &
Intelligence": Osiris'
Race to Market an
FDA-Approved
Stem Cell Product."
GEN. N.p., n.d.
Web. 10 July 2014.
just being ‘recycled’. The cells taken from the bone marrow
will easily form more bone cells, so there is very little
uncertainty on how the stem cells will differentiate. The
cells are autologous so they will not trigger any immune
responses. These stem cells will be seeded into the
microsphere scaffold and the Trabecular Metal just before
insertion into the bone, and then those stem cells will
differentiate and proliferate after implantation. Mesenchymal
stem cells are isolated using a centrifuge, placed in vitro, then
seeded into the joint replacement to grow after implantation.
While the osteocytes and fibroblasts are growing into the joint replacement,
biodegradable calcium sulfate bone cement will hold it in place. Tests have shown that
calcium sulfate bone cement was completely reabsorbed and replaced by a large amount
of new bone in around two months (Rechenberg et al. 2013). One example of calcium
sulfate based bone cement is BoneSource®, a biocompatible, durable, osteoconductive,
and easily sculptable material (Stryker 2004). The bone cement is manufactured as
calcium phosphate powders that would then be mixed with a liquid solution to form a
paste or cement.
The growth factors that are to be inserted into the dense microsphere scaffold
and slowly released over time are: IGF-1, BMP-2, and TGF beta. IGF-1 (insulin like
growth factor) stimulates an increase in hypertrophy and hyperplasia of many tissues,
including bone tissue (Utiger). The addition of this growth factor would encourage cell
proliferation and the increased cell size of cells in the joint replacement. BMP-2 has a
“pivotal role in the regulation of bone induction, maintenance and repair” (Sykaras

10. 2003). TGF beta is a “stimulator of osteoblastic bone formation, causing chemotaxis,
proliferation and differentiation in committed osteoblasts” (Mundy 1991). IGF, BMP,
and TGF beta are all naturally present in bones and affect the proliferation and
differentiation of osteoblasts (Linkhart 1996). The combination of these three main
growth factors demonstrate high applicability to increasing bone formation, promoting
healing of bone fractures, and inducing bone growth around implants (Linkhart 1996);
For these reasons IGF, BMP, and TGF beta especially applicable to joint replacements.
This unique combination of cells, scaffolds, and growth factors should result in a
flexible, biocompatible, and well integrated joint replacement. After the hydrogel
scaffold and tissue adhesive have fully degraded, all that will remain is the Trabecular
Metal scaffold that is being held in place by mature osteocytes and fibroblasts. This
design creates the perfect balance of natural and artificial materials for the optimal
performance of the new joint.
Device Testing:

11. Image From:
http://madsculp
tor.blogspot.co
m/2011/01/saty
r-legs-day-
60.html
When testing this device our primary concern is
bone ingrowth and the effects that stem cells seeded in
an artificial joint have on it. We are also concerned with
the strength of short-term bone cement as we do not
want it to fail while the bone is still growing into the
metal implant. The joint replacement should be able to
withstand the rigors and stresses of movement, have
sufficient mobility, and integrate into the natural tissues
of the organism.
To test this, we are going to implant this device in several goats, which can be
used for testing orthopedic prosthesis due to similarities in joint structure. The joint will
be X-rayed to check for any loosening and bone ingrowth two weeks after implantation.
It will be checked again every month after implantation for a year, and then once a year
after that. The joint will be tested for range of movement, flexibility, and ability to
withstand the stresses of movement once each week. The goats will be observed and any
handicaps of movement will be recorded and its progress will be closely monitored. All
of this data will be compared to a healthy goat as a control to see how well it mimics a
natural, healthy joint.
Because the basic structure of the joint mechanism is not changing, we are not
looking for anything involving the joint itself, instead only looking at how well the
prosthesis integrates with the bone and how durable that integration is. The results will
then be analyzed and the applicability of the Orthogenua Joint Replacement in humans.
How We Change the Status Quo:

12. In modern times, joints last a minimal period of time, and specifically in the
knee, last between 10-15 years. This time span is further shortened by the fact that
athletes often require knee joint replacements, and they apply added stress to these
joints. While we don’t change the type of replacement, we change the cement to offer a
longer lasting joint, because the better material offers more resilience and naturally
blends with the tissue over time because of our use of the autologous cells. Therefore our
project does improve the “Status Quo”, and we have achieved something that can truly
change joint replacement.
Conclusion:
Overall, with our use of the joint replacement made from Trabecular Metal and adhered
to that metal using a biodegradable and biocompatible gecko-inspired tissue adhesive is
a highly porous layer of microsphere scaffolding that is engineered to release the growth
factors. Also,
Future Developments:
While our method for implanting artificial joints is an improvement upon already
existing techniques, it still has the disadvantages associated with the use of non-
biological components such as metals and plastics, which will wear down over time and
will not be repaired by the body. To completely negate these effects we would need to
design a joint that is completely made of the patient’s tissue, potentially allowing it to be
repaired by the body in the event of damage or wear. However, we do not currently have
the techniques to reliably and completely remake hard tissue suitable for use in the
body, and joints are further complicated as they require tendons, ligaments, and

13. cartilage to function and these cannot be reliably produced with the correct mechanical
properties. Despite these difficulties, our developments regarding bone regrowth into
artificial joints should help further research into orthopaedic scaffolds and ingrowth,
potentially allowing someone to completely recreate bones.
While many of potential uses of this device are academic in nature, it does
present immediate solutions to many problems. The most obvious of these is that it can
be adapted for use in other joints besides the knee, but there are other uses as well. One
example is traumatic injuries, which, in more severe cases, can leave people missing
sections of bone. In the event of such an injury the trabecular metal and microsphere
scaffold, once properly shaped and seeded with mesenchymal stem cells, could be used
to replace the missing section of bone. If adhered with calcium sulfate bone cement the
bone would grow into the trabecular metal relatively quickly, leaving a naturally
attached section of bone and metal to replace what had to be removed.
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