Knee cartilage replacement therapy
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 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 apoptosis. There are several different repair options available for cartilage damage or failure.
Osteoarthritis 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 bracesand 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.
This type of repair, short of total joint replacement, can be divided into three groups.
Treatments that remove the diseased and undermined cartilage with an aim to stop inflammation and pain include shaving (chondrectomy) and debridement.
Another group of treatments consists of a range of abrasive procedures aimed at triggering cartilage production, such as drilling, microfracture surgery, 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 thesubchondral bone.
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, which is also known as AMIC, is a biological treatment option for articular cartilage damage 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.
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).
One ACI treatment, called Carticel, is designated for young, healthy patients with medium to large sized damage to cartilage and is not applicable to osteoarthritis patients. The patient’s 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. 10,000 cells are harvested and grown in vitro for approximately six weeks until the population reaches 10-12 million cells. Then these cells are injected into the patient. These cells are held in place by a small piece of soft tissue from the tibia, called a periosteal flap, which is sutured over the area to serve as a watertight lid. The implanted chondrocytes then divide and integrate with surrounding tissue and potentially generate hyaline-like cartilage.
A variation on the Carticel technique, called matrix-associated autologous chondrocyte transplantation (MACT), grows the patient's cells in a 3D matrix of resorbable tissue which is implanted via an open or arthroscopic procedure. It appears to be a simpler technique and resolves some of the issues of using Carticel under a periosteal patch.
Another ACI technique, using "chrondospheres", uses only chrondrocytes and no matrix material. The cells grow in self-organized spheroid matrices which are implanted via injected fluid or inserted tissue matrix.
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.
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, known as mosaicplasty, is described in the next paragraph.
There are three methods of grafting cartilage defects:
Total knee replacement 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 outcome from surgery indicating 85% of patients are happy with the procedure, approximately 10% do not see a significant improvement and 5% report worsening of symptoms. 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. Women undergo the procedure more often than men, making up 60% of the patient population.
