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 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.

Non-surgical treatments
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 braces and drug therapies, such as anti-inflammatories (ex. diclofenac, ibuprofen, and naproxen), COX-2 selective inhibitors, hydrocortisone, glucosamine, and chondroitin sulfate, 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 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. Laser assisted treatments, currently experimental, compose a third category; they combine the removal of diseased cartilage with cartilage reshaping and also induce cartilage proliferation.

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.

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 plate of the 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.

Autologous chondrocyte implantation (ACI) and Carticel®
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). In the United States, Genzyme Corporation provides the only FDA approved ACI treatment, Carticel.

The Carticel treatment is designated for young, healthy patients with small to medium 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 chondyles. 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 on the cartilage defect by a periosteal flap, a small piece of bone tissue sutured over the damaged area. 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 (Freiburg, Germany) has since moved the CARTICEL® technology forward. A patients 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 seeded on collagenic sferoids and then implanted through a syringe.

Osteochondral Autograft (OATS)
This technique/repair 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, chondral 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. However, ACI is a common practice today that involves the use of perichondrial grafts, of which Carticel is the only FDA approved procedure. Mosaicplasty, a form of chondral grafting, is a therapy designed to stimulate growth of articular 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 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 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.