CARTILAGE REPAIR
Topics
Overview - Arthritis
Cartilage Transplants
Microfracture
Osteochondral Transplants
Synthetic Plugs
Rehabilitation After Cartilage Repair
Gallery
Transplant Outcomes
The concept of using live cartilage cells from a patient to repair defects in that patient's cartilage was developed in the 1980s, in Sweden. Because cartilage does not naturally repair itself, it was thought, perhaps tissue culture of the cells—in a laboratory setting—could expand them to a sufficient volume to fill what is a essentially a defect, or a hole, in the cartilage layer. There are several problems with this idea, however, including safety and sterility of the cells, the need for two operations, and the requirement that the cells be somehow held in place—lest they fall out of the defect before any healing at all can occur.
To address the last problem, a “patch” was needed that could be affixed to the defect. This was originally developed to be a piece of “periosteum” or bone cover, that can be peeled off the bone like a postage stamp and carefully sutured to the cartilage edges. The surgical technique is extremely difficult, requiring very small sutures, magnification, and the ability to work deep inside the body—and sometimes around curves! Although effective, one disadvantage of periosteum is that sometimes it has growth properties of its own—and can overgrow the area. Newer techniques are being worked out that use more inert patches, or even avoid the idea of a patch altogether.
The correct term for cartilage transplantation is “ACI”: autologous cartilage transplantation. The first step in this procedure is to obtain a small biopsy, about the size of a “tic-tac”, for the inner aspect of the knee (the intercondylar notch) where there is no weight bearing. This is thought to be an innocuous place to remove a small amount of cartilage, and usually is in good repair even in damaged knees. The obvious risk in doing this is that even though the cartilage may look normal, there is no guarantee that biochemically it really is normal. More on this later.
The biopsy specimen is sent in a special container to the Genzyme lab in Cambridge, Mass. There, they remove the hard matrix in which the cartilage cells (chondrocytes) are normally embedded. They then take the cells, which comprise only a small part of the volume of normal cartilage, and place them in tissue culture. With appropriate nutrients, and under the right conditions (including maximal sterility), the cells grow for about ten days. Then they are frozen in liquid nitrogen. The cells are kept normally for about a year while a decision is made to perform ACI.
Prior to the actual transplant the cells are defrosted and grown for a period of about two to three weeks, depending upon the sample, the growth characteristics, and the volume needed. Normally they are expanded to about 12 million cells.
Prior to FDA approval of this procedure (1997), basic assays for Type II collagen, which is found in normal cartilage, were indicative of promising results for these cultured cells. In other words, there was some basis to believe that in spite of all the manipulation discussed above, the grown cells were showing evidence that at least in some respects they were behaving like normal cartilage. This is assumed to be good news for the patients! It would be of interest to apply more modern methods of genomics and proteomics to further validate that the engineered tissue is approximating normal tissue.
A recent study sponsored by Tigenix has demonstrated that the use of cartilage specific biomarkers can improve results in some ACI patients; those cells with poor characteristics are not accepted for transplantation.
These photos demonstrate a large lesion of the inside of the knee (medial femoral condyle) that almost takes up the entire weight bearing surface.
This defect is over 6 square centimeters. There is evidence that ACI is just as effective for large lesions as it is for small ones; the technique is more limited by technical considerations (what you can get to through a certain incision) than it is by size of the lesion.
Here we see that periosteal patch affixed to the lesion using both sutures and small absorbable tissue anchors. This is a tedious procedure as it involves suturing around a curved surface through a small incision. After the procedure, which is performed at an outpatient surgicenter, the patient is placed comfortably on a machine that moves the knee slowly through a cycle of motion. The machine is used 6-8 hours/day for about 10 days. Also, the patient is kept on crutches for 4 weeks so as to not disturb the “patch” while the new cartilage cells are growing.
Microfracture
The most common procedure currently in use for cartilage repair is microfracture, which really means making a series of tiny holes (with a special awl) in order to stimulate the stem cells of the bone marrow. We all have stem cells in the bone marrow throughout life, but the prevalence of these cells is about 1 in 10,000, and decreases with age. The idea is to release these cells into the hole created by the loss of cartilage. If the cells form a clot, there is a good chance that some may start to grow into a new tissue that in some sense resembles cartilage, even if not perfectly; it is certainly better than no fill of the hole at all.
Microfracture requires the same rehabilitation protocol as ACI, but it has the advantage of being performed arthroscopically. It is therefore considerably less expensive, and on that score alone has been promoted by many as being a “first line” approach. By this it is meant that if microfracture fails, the option for ACI or other techniques is still open. Insurance companies sometimes react positively when confronted with the information that microfracture has already been tried to heal a cartilage lesion.
Microfracture works especially well for small cartilage holes, and is considerably more successful in young people. Nevertheless, the success rates are variously quoted as between 60-75% even in the best hands and with the most motivated patients. This large a failure rate is not typical for other orthopaedic procedures (ACI will succeed apprx. 90% of the time), so of course the patient should know just what the odds are before embarking on the microfracture protocol, which really means an investment of about one year. Patient compliance and willingness to take directions is totally essential for microfracture! It may be for this reason, amongst others, that the well motivated young athlete has a higher success rate than the typical patient.
Patients are instructed that the rehab must go according to protocol, and especially as regards return to impact sports, that decision cannot be made by the patient alone or on the basis of how the patient feels. In other words, stay with the recipe, no embellishments. This problem has been reported in the popular press when professional athletes sometimes are allowed to return too early—this may result in repeat surgery.
My approach is to match the best procedure to a particular patient. The size of the cartilage lesion, the location, the age of the patient, the work situation—which sometimes means: is the patient willing to undergo the rehab twice (if the microfracture fails); all of these factors contribute to the decision to proceed with microfracture, to perform ACI or—in some cases—to not perform cartilage repair. This latter decision is particularly difficult to make, but it does appear to be logical as patients age and the possibility of a total knee replacement appears less daunting.
Stay tuned for procedures in the works that increase the efficacy of microfracture without requiring the growth of cells.
Reference: "The Microfracture Technique for the Treatment of Articular Cartilage Lesions in the Knee" in The Journal of Bone & Joint Surgery
Osteochondral Transplants
One convenient way to repair cartilage defects is to obtain a combination of cartilage with its underlying bone—usually in the shape of a cylinder—and make a corresponding empty hole in which to insert the new “plug”. In this way the cartilage layer is already attached to bone and the blood supply may eventually integrate the new graft into the surrounding tissues. This can be performed either with bone from the patient (autograft) or from a cadaver donor (allograft). Of course there are advantages and problems associated with either source of tissue. A common theme of this idea is that a cartilage replacement plug can be inserted arthroscopically and sized precisely to match the size of the cartilage defect.
Autografts are safe because they come from the patient, and there is no issue of disease transmission. The donor sites for autograft are the peripheral areas of knee cartilage, and the surgeon has to use careful judgment in deciding just how much of this tissue is expendable- The procedure is essentially robbing Peter to pay Paul. So a reasonable autograft, sometimes called a mosaicplasty, is usually a very small cylinder of cartilage and bone, or perhaps several.
Allografts are from a cadaveric donor. Although any good tissue bank performs routine screening for HIV, hepatitis, bacteria, etc., and there are now standards for tissue banks to observe, disease transmission is not an unknown complication of tissue banking. The popular press has exposed several instances of multiple patients receiving diseased tissue in a variety of organ systems. Nevertheless, the concept of pre-packaged osteochondral grafts in a variety of sizes, and without size limitation, is quite attractive. Unlike other tissues, there is not thought to be a significant immune problem when allografts are placed into a joint (immunoprotected).
Fresh allograft material, which has live cartilage cells, is thought to be far more favorable that conventional frozen allografts, although the latter are safer. Very recent developments may allow us to have the best of both worlds—a safe, frozen allograft with live cartilage cells in it. Stay tuned for this possibility in the very near future.
Rehabilitation After Cartilage Repair
Rehabilitation, always an important—some would say crucial—aspect of orthopaedic care, has some common elements for all cases and then some specific elements that depend upon the location of the cartilage lesion. I like to say that physical therapy for cartilage reconstruction is site specific.
One common element is that post operative motion is, in general, thought to be beneficial for the repairing cartilage cells. This was originally shown by Dr. Robert Salter, and it seems to hold true no matter what the repair technique is. One way of encouraging rapid post operative motion is to use a "continuous passive motion," or CPM device, which is essentially a slow moving sled that sits on the bed. It is quite comfortable for most patients, and is often used 6-8 hours/day (which can be while sleeping). In a typical case, the motion is gradually increased day by day by having the patient move a dial. Some cartilage procedures may be combined with other procedures (like tibial tuberosity osteotomy) that force us to restrict the motion for a while. Eventually, the goal is to get back full motion. These machines are usually used for two to three weeks.
During the motion phase, patients use two crutches and do not walk upon the leg. Squatting or stair climbing is forbidden. However, it is okay to balance slightly on the foot, or to rest the foot upon the ground. Some patients with cartilage defects underneath the kneecap are allowed to place even more weight on the leg at about ten days.
Isometrics, good leg control, and return of motion are the initial goals. The therapist can be very helpful during this time—but even if the patient meets these goals early, advancement of therapy must await the appropriate time! We do not want to put too much stress upon the graft when it is very early in the growth phase.
Sometimes these are called “open chain” exercises. In a few weeks, we convert to “closed chain” exercise, which means: increasing the load, putting the foot upon the floor. One effective way of doing this is to use a stationary bike at no load (like a flywheel) and then gradually increase the load. Swimming—especially treading water—is also a good method. At about six weeks progressive resistance exercises are valuable as we smoothen out the gait. Usually the patients are feeling very good at this time, and we have to hold them back from overdoing it—for months! There are many activities allowed, such as biking, elliptical training, swimming, but other activities such as running and contact sports, are usually not permitted for one year. In the professional athlete population, there is ample evidence that a return to sport too soon—even with a small cartilage defect—does not result in good play.
Patient back to running marathons 2 years after transplantation.
Many of our patients are extremely active. They may never have truly normal joint function; however, every reasonable effort will be made to get people back into those activities which they enjoy.
Patient working at rehab after transplant.