Knee cartilage replacement therapy
Encyclopedia
Articular cartilage, 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
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 articulating 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
apoptosis
. There are several different repair options available for cartilage damage or failure.
is the second leading cause of disability in the elderly population in the United States. It is a degenerative disorder that generally starts off relatively mild and escalates with time and wear. For those patients experiencing mild to moderate symptoms, the disorder can be dealt with by several non-surgical treatments. The use of braces and drug therapies, such as anti-inflammatories (ex. diclofenac
, ibuprofen
, and naproxen
), COX-2 selective inhibitors, hydrocortisone,have been shown to alleviate the pain caused by cartilage deficiency and some claim they may slow the degenerative process.
, can be divided into three groups.
.
It is interesting to note that debridement
, introduced by Magnuson
in 1941, does not have any scientific basis for existence; in fact, it is deleterious in terms of knee biomechanics. It is used palliatively as it temporarily relieves pain associated with arthritic inflammation. Many insurance companies (ex. Aetna
) consider the procedure experimental because there is no evidence proving its effectiveness.
, chondroplasty
, and spongialization.
Abrasion, drilling, and microfracture originated 20 years ago. They rely on the phenomenon of spontaneous repair of the cartilage tissue following vascular injury to the subchondral bone.
Laser abrasion provides gentle cutting of the cartilage. It uses heat to induce alterations in the physical matrix, which results in shape change and stress reduction. Improving this therapy to make it more spatially selective would avoid excessive tissue damage such as air bubble formation, tissue necrosis, reactive synovitis, chondrolysis, and an acceleration of articular cartilage degeneration.
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
.
A systematic review was published in 2010 evaluating the evidence for autologous chondrocyte implantation. 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.
In the United States, Genzyme Corporation provides the only FDA approved ACI treatment, Carticel. The Carticel treatment is designated for young, healthy patients with medium to large sized damage to cartilage. The procedure is not applicable to osteoarthritis patients.
During an initial procedure, the patient’s own chondrocytes 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. The 10,000 cells that are originally harvested are grown in vitro at Genzyme biosurgery for approximately six weeks until the population reaches 10-12 million cells. After this cell proliferation period, the patient undergoes a second surgery in which the millions of chondrocytes are surgically injected into the patient. These cells are held in place by a periosteal flap, a small piece of soft tissue from the tibia, which is sutured over the damaged area to serve as a watertight lid. The implanted chondrocytes can then divide and integrate with surrounding tissue under the flap and potentially generate hyaline
-like cartilage.
Though Carticel has not been studied as an effective procedure through a wide range of patient backgrounds, results suggest that some patients can return to pre-injury function. Over 10,000 procedures have been performed since Carticel was introduced in 1995, and approximately 1,500-3,000 are performed per year. The cost of the treatment ranges from $20,000-$35,000. CARTICEL II is the second generation of the CARTICEL procedure. It is uses a "Fleece matrix" into which the grown harvested chondrocyte cells are planted. This fleece is then re-introduced back into the body usually via arthroscopy to begin the healing process. This CARTICEL II procedure is about to undergo clinical trials under the supervision of the FDA in the United States. This newer technique is known as matrix autologous chondrocyte implantation or (MACI). It is also available in Germany, UK, and Australia.
BioTissue Technologies GmbH http://www.biotissue.de/ (Freiburg, Germany) has since moved the CARTICEL technology forward. A patient's hyaline biopsy is taken, sent to their lab and grown into a 3D matrix of resorbable tissue. This matrix is then supplied back to the surgeon who then implants it back into the patient either via an open or arthroscopic procedure. It appears to be a lot simpler technique and resolves some of the issues of using Carticel under a periosteal patch. Other companies offering similar products include FAB (Fidia Advanced Biopolymers), Geistlich Biomaterials and Arthro Kinetics.
Another German company, co.don AG (URL http://www.codon.de/) has recently launched a treatment called CHONDROSPHERE, which represents an evolutionary third generation compared to Genzyme's first generation liquid product or BioTissue Technologies' second generation 3D matrix. CHONDROSPHERE technology is 100% autologous as no synthetic/animal/human donor material is used in its production. The cells are building spheroids with an average diameter of 1mm by producing their own matrix which is then implanted through a syringe.
surgery followed by postoperative injections of autologous peripheral blood progenitor cells(PBPC's) and hyaluronic acid
(HA). PBPC’s are a blood product containing mesenchymal stem cells and is obtained by mobilizing the stem cells into the peripheral blood. Dr. Khay Yong Saw and his team propose that the microdrilling surgery creates a blood clot scaffold on which injected PBPC’s can be recruited and enhance chondrogenesis at the site of the contained lesion. They explain that the significance of this cartilage regeneration protocol is that it is successful in patients with historically difficult-to-treat grade IV bipolar or bone-on-bone osteochondral lesions.
Dr. Saw and his team are currently conducting a larger randomized trial and working towards beginning a multicenter study. The work of the Malaysian research team is gaining international attention.
is reserved for the most severe and recalcitrant forms of osteoarthritis. When other forms of treatment fail or when patients are unlikely to succeed with lesser therapies, the last option to treat defective cartilage is to replace all or part of the joint. In knee joint replacement, the worn out surfaces of the knee are resurfaced with metal and plastic, replacing the poorly functioning natural joint with new surfaces that slide together smoothly. The dysfunctional joint is removed and pain is relieved. Total knee replacement is considered a relatively routine surgery with a 95% success rate at 20 years. There are more than 300,000 total knee replacements in the United States each year. The average patient age is between 65 and 75. Of these surgeries, approximately 80% are unilateral (only one knee replaced) and 20% are bilateral. Interestingly, women undergo the procedure more often than men, making up 60% of the patient population.
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
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 articulating 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
Chondrocyte
Chondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. There are several different repair options available for cartilage damage or failure.
Non-surgical treatments
OsteoarthritisOsteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
is the second leading cause of disability in the elderly population in the United States. It is a degenerative disorder that generally starts off relatively mild and escalates with time and wear. For those patients experiencing mild to moderate symptoms, the disorder can be dealt with by several non-surgical treatments. The use of braces and drug therapies, such as anti-inflammatories (ex. diclofenac
Diclofenac
Diclofenac is a non-steroidal anti-inflammatory drug taken to reduce inflammation and as an analgesic reducing pain in certain conditions....
, ibuprofen
Ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug used for relief of symptoms of arthritis, fever, as an analgesic , especially where there is an inflammatory component, and dysmenorrhea....
, and naproxen
Naproxen
Naproxen sodium is a nonsteroidal anti-inflammatory drug commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as:...
), COX-2 selective inhibitors, hydrocortisone,have been shown to alleviate the pain caused by cartilage deficiency and some claim they may slow the degenerative process.
Non-biological treatments
This type of repair, short of total joint replacementJoint replacement
Replacement arthroplasty [from Greek arthron, joint, limb, articulate, + -plassein, to form, mould, forge, feign, make an image of], or joint replacement surgery, is a procedure of orthopedic surgery in which the arthritic or dysfunctional joint surface is replaced with an orthopaedic prosthesis...
, can be divided into three groups.
Chondrectomy and debridement
Treatments that remove the diseased and undermined cartilage with an aim to stop inflammation and pain include shaving (chondrectomy) and debridementDebridement
Debridement is the medical removal of a patient's dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue...
.
It is interesting to note that debridement
Debridement
Debridement is the medical removal of a patient's dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue...
, introduced by Magnuson
Magnuson
-Surnames:*Algot Magnuson of Revsnes , medieval Swedish magnate, and castellan of Styresholm*Ann Magnuson , American actress*Christine Magnuson, American swimmer*Princess Christina, Mrs. Magnuson , sister of the King of Sweden...
in 1941, does not have any scientific basis for existence; in fact, it is deleterious in terms of knee biomechanics. It is used palliatively as it temporarily relieves pain associated with arthritic inflammation. Many insurance companies (ex. Aetna
Aetna
Aetna, Inc. is an American health insurance company, providing a range of traditional and consumer directed health care insurance products and related services, including medical, pharmaceutical, dental, behavioral health, group life, long-term care, and disability plans, and medical management...
) consider the procedure experimental because there is no evidence proving its effectiveness.
Abrasion and microfracture surgery
Another group of treatments consists of a range of abrasive procedures aimed at triggering cartilage production, such as drilling, microfracture surgeryMicrofracture surgery
Microfracture surgery is one of the articular cartilage repair surgical techniques that works by creating tiny fractures in the underlying bone. This causes new cartilage to develop from a so-called super-clot...
, chondroplasty
Chondroplasty
Chondroplasty refers to surgery of the cartilage, the most common being corrective surgery of the cartilage of the knee.Surgery known as thyroid chondroplasty is used to reduce the visibility of the Adam's Apple in transsexual women....
, and spongialization.
Abrasion, drilling, and microfracture originated 20 years ago. They rely on the phenomenon of spontaneous repair of the cartilage tissue following vascular injury to the subchondral bone.
Laser-assisted treatments
Laser assisted treatments, currently experimental, compose a third category; they combine the removal of diseased cartilage with cartilage reshaping and also induce cartilage proliferation.Laser abrasion provides gentle cutting of the cartilage. It uses heat to induce alterations in the physical matrix, which results in shape change and stress reduction. Improving this therapy to make it more spatially selective would avoid excessive tissue damage such as air bubble formation, tissue necrosis, reactive synovitis, chondrolysis, and an acceleration of articular cartilage degeneration.
Autologous matrix-induced chondrogenesis
Autologous matrix-induced chondrogenesis, which is also known as AMIC, is a biological treatment option for articular cartilage damageArticular cartilage damage
Cartilage structures and functions can be damaged. Such damage can result from a variety of causes, such as a bad fall or traumatic sport-accident, previous knee injuries or wear and tear over time...
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
Mesenchymal stem cell
Mesenchymal stem cells, or MSCs, are multipotent stem cells that can differentiate into a variety of cell types, including: osteoblasts , chondrocytes and adipocytes...
released through microfracture and enhances their chondrogenic differentiation
Chondrogenesis
-Cartilage in fetal development:In embryogenesis, the skeletal system is derived from the mesoderm germ layer. Chondrification is the process by which cartilage is formed from condensed mesenchyme tissue, which differentiates into chondrocytes and begins secreting the molecules that form the...
.
Autologous chondrocyte implantation
Despite advances in materials science and innovations in knee repair, no current therapy can mimic the extraordinary biomechanical properties of cartilage. This notion drives initiatives in cell-based replacement technologies, such as autologous chondrocyte implantation (ACI).A systematic review was published in 2010 evaluating the evidence for autologous chondrocyte implantation. 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.
In the United States, Genzyme Corporation provides the only FDA approved ACI treatment, Carticel. The Carticel treatment is designated for young, healthy patients with medium to large sized damage to cartilage. The procedure is not applicable to osteoarthritis patients.
During an initial procedure, the patient’s own chondrocytes 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. The 10,000 cells that are originally harvested are grown in vitro at Genzyme biosurgery for approximately six weeks until the population reaches 10-12 million cells. After this cell proliferation period, the patient undergoes a second surgery in which the millions of chondrocytes are surgically injected into the patient. These cells are held in place by a periosteal flap, a small piece of soft tissue from the tibia, which is sutured over the damaged area to serve as a watertight lid. The implanted chondrocytes can then divide and integrate with surrounding tissue under the flap and potentially generate hyaline
Hyaline cartilage
Hyaline cartilage consists of a slimy mass, pearly bluish in colour with firm consistency and considerable collagen. It contains no nerves or blood vessels, and its structure is relatively simple....
-like cartilage.
Though Carticel has not been studied as an effective procedure through a wide range of patient backgrounds, results suggest that some patients can return to pre-injury function. Over 10,000 procedures have been performed since Carticel was introduced in 1995, and approximately 1,500-3,000 are performed per year. The cost of the treatment ranges from $20,000-$35,000. CARTICEL II is the second generation of the CARTICEL procedure. It is uses a "Fleece matrix" into which the grown harvested chondrocyte cells are planted. This fleece is then re-introduced back into the body usually via arthroscopy to begin the healing process. This CARTICEL II procedure is about to undergo clinical trials under the supervision of the FDA in the United States. This newer technique is known as matrix autologous chondrocyte implantation or (MACI). It is also available in Germany, UK, and Australia.
BioTissue Technologies GmbH http://www.biotissue.de/ (Freiburg, Germany) has since moved the CARTICEL technology forward. A patient's hyaline biopsy is taken, sent to their lab and grown into a 3D matrix of resorbable tissue. This matrix is then supplied back to the surgeon who then implants it back into the patient either via an open or arthroscopic procedure. It appears to be a lot simpler technique and resolves some of the issues of using Carticel under a periosteal patch. Other companies offering similar products include FAB (Fidia Advanced Biopolymers), Geistlich Biomaterials and Arthro Kinetics.
Another German company, co.don AG (URL http://www.codon.de/) has recently launched a treatment called CHONDROSPHERE, which represents an evolutionary third generation compared to Genzyme's first generation liquid product or BioTissue Technologies' second generation 3D matrix. CHONDROSPHERE technology is 100% autologous as no synthetic/animal/human donor material is used in its production. The cells are building spheroids with an average diameter of 1mm by producing their own matrix which is then implanted through a syringe.
Autologous mesenchymal stem cell transplantation
For years, the concept of harvesting stem cells and re-implanting them into one's own body to regenerate organs and tissues has been embraced and researched in animal models. In particular, mesenchymal stem cells have been shown in animal models to regenerate cartilage. Recently, there have been several published case reports of successful cartilage growth in human knees using autologous cultured mesenchymal stem cells. In addition, an n=229 safety study has also been published showing safety better than surgical alternatives for this cultured cell injection procedure at a 3 year follow-up. An advantage to this approach is that a person's own stem cells are used, avoiding transmission of genetic diseases.Microdrilling augmented with peripheral blood stem cells
A 2011 study reports histologically confirmed hyaline cartilage regrowth in a 5 patient case-series, 2 with grade IV bipolar or kissing lesions in the knee. The successful protocol involves arthroscopic microdrilling/ microfractureMicrofracture surgery
Microfracture surgery is one of the articular cartilage repair surgical techniques that works by creating tiny fractures in the underlying bone. This causes new cartilage to develop from a so-called super-clot...
surgery followed by postoperative injections of autologous peripheral blood progenitor cells(PBPC's) and hyaluronic acid
Sodium hyaluronate
Sodium hyaluronate is the sodium salt of hyaluronan. The name hyaluronic acid is derived from the Greek word ύαλος meaning vitreous, and uronic acid as it was first isolated from the vitreous humour in the eye and possesses a high uronic acid content. The term hyaluronate also refers to the...
(HA). PBPC’s are a blood product containing mesenchymal stem cells and is obtained by mobilizing the stem cells into the peripheral blood. Dr. Khay Yong Saw and his team propose that the microdrilling surgery creates a blood clot scaffold on which injected PBPC’s can be recruited and enhance chondrogenesis at the site of the contained lesion. They explain that the significance of this cartilage regeneration protocol is that it is successful in patients with historically difficult-to-treat grade IV bipolar or bone-on-bone osteochondral lesions.
Dr. Saw and his team are currently conducting a larger randomized trial and working towards beginning a multicenter study. The work of the Malaysian research team is gaining international attention.
Osteochondral autograft
Osteochondral autograft (OATS) is a technique that requires that the surgeon transplant sections of bone and cartilage. First, the damaged section of bone and cartilage is removed from the joint. Then a new healthy dowel of bone with its cartilage covering is removed from the same joint and transplanted or grafted into the hole left from removing the old damaged bone and cartilage. The healthy bone and cartilage are taken from areas of low stress in the joint so as to prevent weakening the joint. Depending on the severity and overall size of the damage multiple plugs or dowels may be required to adequately repair the joint. A similar treatment is known as mosaicplasty, and is talked about in the next paragraph.Grafting
There are three methods of grafting cartilage defects, including periosteal grafting, osteochondral grafting (mosaicplasty), and articular cartilage paste grafting. Periosteal grafts are harvested from the perichondrial tissue and grafted to the articular cartilage defect. Given low long-term success rates, perichondrial grafting alone has not been clinically accepted as a particularly excellent therapy. Mosaicplasty, a form of chondral grafting, is a therapy designed to replace cartilage on the surface of the knee joint that has been damaged by trauma or arthritis by implanting osteochondral plugs. The implants can be autogenic (autologous) or allogenic. Paste grafting involves replacing damaged cartilage with autologous cartilage and cancellous bone from the intercondylar notch in the center of the knee that is first morselized into a paste (typically with hydroxyapatite) to better fill the defect and more successfully promote chondrocyte activity and cartilage formation. These procedures are often performed arthroscopically.Joint replacement
Total joint replacementJoint replacement
Replacement arthroplasty [from Greek arthron, joint, limb, articulate, + -plassein, to form, mould, forge, feign, make an image of], or joint replacement surgery, is a procedure of orthopedic surgery in which the arthritic or dysfunctional joint surface is replaced with an orthopaedic prosthesis...
is reserved for the most severe and recalcitrant forms of osteoarthritis. When other forms of treatment fail or when patients are unlikely to succeed with lesser therapies, the last option to treat defective cartilage is to replace all or part of the joint. In knee joint replacement, the worn out surfaces of the knee are resurfaced with metal and plastic, replacing the poorly functioning natural joint with new surfaces that slide together smoothly. The dysfunctional joint is removed and pain is relieved. Total knee replacement is considered a relatively routine surgery with a 95% success rate at 20 years. There are more than 300,000 total knee replacements in the United States each year. The average patient age is between 65 and 75. Of these surgeries, approximately 80% are unilateral (only one knee replaced) and 20% are bilateral. Interestingly, women undergo the procedure more often than men, making up 60% of the patient population.
See also
- Knee replacementKnee replacementKnee replacement, or knee arthroplasty, is a surgical procedure to replace the weight-bearing surfaces of the knee joint to relieve the pain and disability of osteoarthritis. It may be performed for other knee diseases such as rheumatoid arthritis and psoriatic arthritis...
- Hip replacementHip replacementHip replacement is a surgical procedure in which the hip joint is replaced by a prosthetic implant. Hip replacement surgery can be performed as a total replacement or a hemi replacement. Such joint replacement orthopaedic surgery generally is conducted to relieve arthritis pain or fix severe...
- Replacement jointReplacement jointReplacement arthroplasty [from Greek arthron, joint, limb, articulate, + -plassein, to form, mould, forge, feign, make an image of], or joint replacement surgery, is a procedure of orthopedic surgery in which the arthritic or dysfunctional joint surface is replaced with an orthopaedic prosthesis...
- CartilageCartilageCartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
- Meniscal cartilage replacement therapyMeniscal Cartilage Replacement TherapyThe meniscus is a C-shaped piece of fibrocartilage located at the peripheral aspect of the knee joint that offers lubrication and nutrition to the joint. Each knee has two menisci, medial and lateral, whose purpose is to provide space between the tibia and the femur, preventing friction and...