Knee Cartilage Replacement Therapy
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Articular cartilage Hyaline cartilage is the glass-like (hyaline) and translucent cartilage found on many joint surfaces. It is also most commonly found in the ribs, nose, larynx, and trachea. Hyaline cartilage is pearl-gray in color, with a firm consistency and has ...
, most notably that which is found in the knee joint, is generally characterized by very low friction, high wear resistance, and poor regenerative qualities. It is responsible for much of the compressive resistance and load bearing qualities of the knee joint and, without it, walking is painful to impossible.
Osteoarthritis Osteoarthritis is a type of degenerative joint disease that results from breakdown of articular cartilage, joint cartilage and underlying bone. A form of arthritis, it is believed to be the fourth leading cause of disability in the world, affect ...
is a common condition of cartilage failure that can lead to limited range of motion, bone damage and invariably, pain. Due to a combination of acute stress and chronic fatigue, osteoarthritis directly manifests itself in a wearing away of the articular surface and, in extreme cases, bone can be exposed in the joint. Some additional examples of cartilage failure mechanisms include cellular matrix linkage rupture, chondrocyte protein synthesis inhibition, and
chondrocyte Chondrocytes (, ) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. Although the word '' chondroblast'' is commonly used to describe an immatu ...
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
. There are several different repair options available for cartilage damage or failure. "Maci" or autologous cultured
chondrocytes Chondrocytes (, ) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. Although the word '' chondroblast'' is commonly used to describe an immatu ...
on
porcine The pig (''Sus domesticus''), also called swine (: swine) or hog, is an omnivorous, domesticated, even-toed, hoofed mammal. It is named the domestic pig when distinguishing it from other members of the genus '' Sus''. Some authorities consid ...
collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
membrane, is a treatment to correct
cartilage Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...
defects in the knee. This treatment has been approved by the
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
in 2016 for adult treatment only.


Autologous matrix-induced chondrogenesis

Autologous matrix-induced chondrogenesis, which is also known as AMIC, is a biological treatment option for
articular cartilage damage The articular bone is part of the lower jaw of most vertebrates, including most jawed fish, amphibians, birds and various kinds of reptiles, as well as ancestral mammals. Anatomy In most vertebrates, the articular bone is connected to two othe ...
bone marrow stimulating technique in combination with a collagen membrane. It is based on the microfracture surgery with the application of a bi-layer collagen I/III membrane. The AMIC technique was developed to improve some of the shortfalls of microfracture surgery such as variable repair cartilage volume and functional deterioration over time. The collagen membrane protects and stabilizes the MSCs released through microfracture and enhances their chondrogenic differentiation. The AMIC surgery is a single-step procedure. Once cartilage damage is assessed there are two methods to access the joint to proceed with the AMIC surgery. First is to perform a mini arthrotomy. Second is an all-arthroscopic procedure.


Autologous chondrocyte implantation

The human body's own cartilage is still the best material for lining knee joints. This drives efforts to develop ways of using a person's own cells to grow, or re-grow cartilage tissue to replace missing or damaged cartilage. One cell-based replacement technique is called autologous chondrocyte implantation (ACI) or autologous chondrocyte transplantation (ACT). A review evaluating autologous chondrocyte implantation was published in 2010. The conclusions are that it is an effective treatment for full thickness chondral defects. The evidence does not suggest ACI is superior to other treatments. One ACI treatment, called MACI (autologous cultured chondrocytes on a porcine collagen matrix), is indicated for healthy patients 18–55 with medium to large sized damage to their cartilage. It is not applicable to osteoarthritis patients. The patient's
chondrocytes Chondrocytes (, ) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. Although the word '' chondroblast'' is commonly used to describe an immatu ...
are removed arthroscopically from a non load-bearing area from either the intercondylar notch or the superior ridge of the medial or lateral femoral condyles. 10,000 cells are harvested and grown
in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
for approximately six weeks until the population reaches 10-12 million cells. Then these cells are seeded onto a film that is implanted into the area of cartilage damage and absorbed back into the tissue into the patient. The implanted chondrocytes then divide and integrate with surrounding tissue and potentially generate
hyaline A hyaline substance is one with a glassy appearance. The word is derived from , and . Histopathology Hyaline cartilage is named after its glassy appearance on fresh gross pathology. On light microscopy of H&E stained slides, the extracellula ...
-like cartilage. Another ACI technique, using "chondospheres", uses only chondrocytes and no matrix material. The cells grow in self-organized spheroid matrices which are implanted via injected fluid or inserted tissue matrix. Techniques such as the EELS-TALC to enhance ACI and MACI with enabling chondrocytes to be tissue engineered with long term native knee cartilage phenotype maintenance in vitro and in vivo, with the engineered tissue construct containing stem cell progenitors along with those expressing pluripotency markers and with added advantage of enriched hyaluronic acid (HA) expression by the cells have been reported which will contribute to improvised regenerative therapies for cartilage damage.


Autologous mesenchymal stem cell transplantation

Because
mesenchymal stem cells Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage ...
may regenerate cartilage, cartilage growth in human knees using autologous cultured mesenchymal stem cells is under research and preliminary clinical use, and appears to be safe as of 2016. An advantage to this approach is that a person's own stem cells are used, avoiding tissue rejection by the
immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
. Stem cells enable surgeons to grow replacement cartilage, which gives the new tissue greater growth potential. While there are few long-term studies as of 2018, a history of knee problems and body weight are factors for how well the procedure will work.


Microdrilling augmented with peripheral blood stem cells

A 2011 study reported histologically confirmed hyaline cartilage regrowth in the knee. The successful protocol involved arthroscopic microdrilling/ microfracture surgery followed by postoperative injections of autologous peripheral blood progenitor cells (PBPCs) and
hyaluronic acid Hyaluronic acid (; abbreviated HA; conjugate base hyaluronate), also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminog ...
. The procedure creates a
blood clot A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulatio ...
scaffold on which injected PBPCs can be recruited and enhance chondrogenesis at the site of the contained lesion.


See also

* Meniscal cartilage replacement therapy *
Meniscus transplant A meniscus transplant or meniscal transplant is a transplant of the meniscus of the knee, which separates the thigh bone (femur) from the lower leg bone (tibia). The worn or damaged meniscus is removed and is replaced with a new one from a donor ...
* Spheroids of human autologous matrix-associated chondrocytes


References


External links


Minimally Invasive Total Knee Replacement.
American Academy of Orthopaedic Surgeons. February 2005. * {{Bone, cartilage, and joint procedures Implants (medicine) Orthopedic surgical procedures Cartilage replacement therapy