Anterior cruciate ligament reconstruction was brought to the public eye in
January of 2013 when Robert Griffin III, a Rookie quarterback for the Washington
Redskins, was injured during the NFL wild card game against the Seattle
Seahawks. While he originally went in during surgery to reconstruct Griffin’s
lateral collateral ligament, or LCL, the surgeon, Dr. James Andrews, also redid a
previous reconstruction of the anterior cruciate ligament, or ACL, as well. Injury
to the ACL is one of the most common problems seen by orthopedic doctors and
surgeons in America; therefore, a lot of money and time is spent on researching
the ACL more in depth. However, even with all this research done on the topic,
which ACL reconstruction technique that is best for recovery of its patients is still
greatly debated in the medical world. Reconstruction of the ACL can occur with
an arthroscopic surgery, either with an allograft or autograft, as well as using
mesenchymal stem cells.
The ACL is a ligament in the human body that is located in the knee.
Ligaments are fibrous connective tissues that connect two or more bones in the
body. They are essential for joint stability and provide resistance of extensive
motion of the joints. To understand the reconstruction of an ACL, one must first
understand the anatomy of a knee. The knee is the largest joint in the human
body and its forward motion is limited by the ACL. “Cruciate means “crossing”;
therefore, the anterior and posterior cruciate ligaments “cross” each other to
provide support and stability inside the knee joint. The ACL connects the femur
bone to the tibia bone in the leg. Most ACL injuries are linked to stiff-leg standing,
as well as quick twisting and turning movements of the knee. When an ACL is
injured, a knee has more instability, is swollen, and could possibly have cartilage
damage.
The first noted mention of injury to the knee was Hippocrates of Cos, a
ancient Greek physician, when he took notice of a subluxation of the knee.
Although, he did not know of the ligaments in the knee, he was able to relate his
observations to ligamentous-like injury. Aelius Galenus, a Roman surgeon and
philosopher, later contributed to the Hippocratic understanding of pathology and
medicine. Galenus was unable to dissect human cadavers due to Roman Law,
but rather dissected animals to complete his studies. He was the first to describe
the anatomy of the knee, as well as the first to name the ligaments, ‘ligamenta
genu cruciate’ (Galen).
The modern history of the diagnosis of an ACL tear dates back to 1845
when Amédée Bonnet wrote a formal dissertation on bloody effusions caused by
joint issues. Bonnet was Professor of Surgery at Lyon University and was one of
the first people to discuss the pivot-shift phenomenon of the knee, which
eventually was used to test the instability of a knee. Later, he tested the use of a
hinged knee brace as rehabilitation technique for knee instability. He analyzed an
acute ACL rupture to have occurred by the consequential events. In his “Traite ́
des maladies des articulations”, Bonnet states that three signs that indicate an
ACL rupture were “patients who have no suffered a fracture, a snapping noise,
hemarthrosis, and loss of function are characteristic of ligamentous injury in the
knee” (Bonnet, A.). The first surgeon known to reconstruct an ACL was MayoRobson of Leeds in 1895. Then, in 1917, Hey Groves of Bristol described an
ACL reconstruction much like one of the techniques used today. His description
was of an ACL reconstruction with autologous tissue graft, like the present day
technique of autograft (Schindler OS.).
According to the American Orthopedic Society of Sports Medicine, there
are over 150,000 ACL injuries in the United States yearly. The society also stated
that ACL injuries account for over half a billion dollars in healthcare costs
(Hewitt), (Boden). There are currently two main types of reconstruction that use a
human tendon to replace the patients’ ACL. A human cadaver’s tendon can be
used, allograft, or the patient’s own tendon can be used, autograft, to replace the
torn ligament. Stem cells can also be used to replace a ligament, despite the fact
there is far less research and development of this technique than allografts and
autografts. Although stability, strengthening, and plyometrics exercises are the
best ways to prevent an ACL injury, it is still undetermined with type of
reconstruction is best for a patient recovery, both short and long term.
Autograft describes the surgical process that a tendon or ligament graft of
oneself is used to replace their torn ACL. For an autograft ACL reconstruction,
surgeons most commonly use the patient’s own patellar or hamstring tendon.
The patellar tendon connects the patella (knee cap) to the tibia bone, or
shinbone. An adult patellar tendon can range anywhere from 25 to 30 millimeters
in width. To take the patellar tendon for the graft, the surgeon must take about
one-third of the tendon (roughly 9-10 millimeters) from the center of the tendon to
replace the ACL. Surgeons sometimes prefer using a patellar graft because it
closely resembles the ACL in length. A patellar graft is “bone to bone” healing;
therefore, it is heals quicker than a hamstring graft that must heal into place.
When surgeons take part of the patellar tendon for the graft, they also
must take part of the kneecap bone. This removal of bone has the possibility of
causing anterior knee pain, as well as a fracture or rupture of the patellar tendon.
The hamstring muscles are the group of muscles in the back of the thigh
that are made up by the bicep femoris, semitendinosus and semimembranosus.
The hamstring muscles’ main purposes are knee flexion and hip extension.
During ACL surgery, the surgeon removes two tendons of these muscles and
“bundle” them together to form a replacement ACL. Since the anterior portion of
the knee is not disturbed with this type of graft, anterior knee pain is not usually
an issue. The incisions are usually smaller for this type of graft. Pain from a
hamstring graft usually occurs right after surgery and lessens as strength is
regained in the leg.
However a hamstring graft is not “bone to bone”, so patients with this type
of graft must have a delayed start of rehabilitation with the graft heals into place.
When surgeons go to take a hamstring graft, there is a chance of damaging the
saphenous nerve branches during the process. It is possible that the patient
could face problems with deep knee flexion, due to the weakened hamstring
(Barrett).
Allograft describes the process of using a human cadaver to harvest a
graft to replace a patient’s torn ACL. For an allograft ACL reconstruction,
surgeons most commonly use patellar tendon, hamstring tendon, and Achilles
tendon from a cadaver. An advantage to using an allograft for a reconstruction is
that there is harvest site morbidity from the donor site. There is also no pain or
scars, as well, from the donor site for a graft in an allograft surgery because the
graft is from a cadaver donor.
Allografts, in general, have disadvantages caused by external factors. The
cost of using a graft from a human cadaver is higher than harvesting an
autograft. The availability of human cadavers also limits the use of harvesting
grafts. Allografts also have a higher failure rate than autografts due to bacterial
infection risk and delayed graft incorporation that both lead to an allograft failing
to replace an ACL.
Recent studies have tried to determine whether an autograft or allograft
has a predominately better recovery than the other. However, a common result
has emerged that neither type of graft show better results years after the surgery.
Another downfall of conventional ACL reconstruction, whether it is
allograft or autograft, is the requirement that patients’ must be skeletally mature
before going in for the surgical reconstruction. Conventional adult ACL
reconstruction could potentially cause a growth disturbance in the area of bone
where cartilage grows, between the metaphysis and the epiphysis. This area, the
growth plate, provides humans with longitudinal growth of bones. Conventional
ACL reconstruction usually involves a surgeon drilling a tunnel in the bone
through the area of the growth plates. If the tunnel is drilled in the bone before
the growth plates naturally close themselves, the tunnel could cause the growth
plates to close prematurely. These growth plates are responsible for the length of
the femur and tibia bone. Therefore, trauma or iatrogenic damage to the physeal
can lead a child to not grow properly due to unequal lengths of legs and angular
deformity.
Young children who are not skeletally mature are usually given the option
to postpone their ACL reconstruction until the growth plates are closed. Patients
with complete or partial ACL tears that must seek out nonreconstructive
treatment are more likely to have issues with stability in the knee, as well as
possible future damage to meniscal and articular cartilage (Kosher, MS., 2003).
Although, patients will partial tears have a chance of the ligament naturally
healing. Recent studies have shown that the instability of a knee due to a torn
ACL in children that are not physiologically mature have worse consequences
than stunting the growth in the leg by disturbance of the physeal (Kosher, MS.,
2004).
Mesenchamyl stem cells are adult, non-embryonic multipotent stem cells
that are able to be differientated into different types of cells. Stem cells have
made large advancements in ligament tissue engineering in the last decade.
When an ACL of a knee ruptures, it limits the regenerative ability of the knee.
Stem cells found in a human ACL are able to differentiate into chondrocytes,
osteoblats, and adipocytes. Mesenchamyl stem cells can be used in surgery
through in vitro or coating to try to regenerate the ligament.
To use mesenchamyl stem cells for reconstructive ACL surgery, a harvest
site in either a donor’s ACL or from the damaged ACL of the patient is set up to
reproduce more stem cells. The mesenchamyl stem cells are then injected into
the injury site of the ACL or used for coating of the allograft or autograft of the
ACL reconstruction. Usually human growth factors are injected or coated with the
stem cells for a ligament repair to help with the healing process. These growth
factors include insulin like growth factor I (IGF-I), transforming growth factor
(TGF), platelet derived growth factor (PDGF), growth vascular endothelial growth
factor (VEGF), and epidermal growth factor (EGF). These growth factors help
regulate cellular activities during the healing process of the graft, as well as
ligament cell proliferation (Fan, H.). Human growth factors are major factors in
the influence of the differentiation of mesenchymal stem cells into fibroblasts
(CIR Campus Bio-Medico University).
The Journal of Arthroscopic and Related Surgery published an article that
used rabbits that underwent bilateral ACL constructions to test whether or not the
coating of stem cells around a hamstring autograft would improve the quality and
healing of the graft. The results from this study showed that the grafts coated
with mesenchamyl stem cells formed an intervening zone of cartilage during the
healing of the graft. This zone was in the area that usually produces collagen
fibers and scar tissue, which hinder the recovery of an ACL reconstructive
surgery. Instead of collagen fibers and scar tissues, the zone is made of cartilage
that resembles the chondral enthesis of normal ACL insertions. These
reconstructive ACLs performed better than the controls during the experiments
when it came to testing of biomechanical aspects of the ligament (Arthroscopy).
Because mesenchamyl stem cells are a more recent discovery as surgical
treatment there are very little studies done to support or discourage the use of
them. A study done by the Children’s Hospital of Pittsburgh showed that ACL –
derived CD34(+) cells that were used during reconstruction surgery through in
vitro were beneficial to the tendon-bone healing. The stem cells were able to
increase the processes of angiogenesis and osteogeneis; which resulted in an
increase in biomechanical strength. These cells were also proven to be better
than other groups of cells in their cell proliferation and VEGF secretion capacities
(Mifune, Y.).
Although autograft and allograft ACL reconstructions are the more popular
choice of grafts at this current time, stem cells could develop as a major
treatment for ACL ruptures once more research can be conducted. While
allografts and autografts show the same results years post operation, it is clear
that a new treatment needs to be discovered that cuts down on the pain, as well
as graft healing time, after a surgery. Once mesenchamyl stem cells have been
more thoroughly developed, it is very possible that they could become the new
solution to ACL tears and other ligament replacements that are more
biochemically sufficient.
Arthroscopy: The Journal of Arthroscopic and Related Surgery - November 2004
(Vol. 20, Issue 9, Pages 899-910, DOI: 10.1016/j.arthro.2004.06.035)
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