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.
Dr. Marcus has been working intensively with Zimmer, Inc. on two new cartilage repair products: DeNovo NT and Chondrofix. These promise to be exciting new allograft technologies that will transform the future of cartilage repair.