Restoring Fluid Motion to the Knee:
Dr. Jack Farr's Cartilage Approach
By Tom Keppeler, Knee1 Staff
Cartilage, the tissue responsible both for cushioning the knee and keeping it moving fluidly, receives little attention until something goes wrong with it. If it does become damaged, however, it can become an obsession for a patient: creaky, painful knees can make for long days, painful walks, and sleepless nights. Until about 10 years ago, little was known—and as a result, little was done—about repairing this unique and somewhat mysterious tissue. Luckily, however, cartilage restoration has become a major interest in modern science—and the focus of Dr. Jack Farr's career.
After graduating from Rose Hulman Institute of Technology in 1975, Dr. Farr received his M.D. from Indiana University. He is a member of the American Academy of Orthopedic Surgeons (AAOS), the American Orthopedic Society of Sports Medicine (AOSSM) and the Arthroscopy Association of North America (AANA). One of the more web-savvy physicians Knee1 has encountered; he has a major role in MyKnee.MD, as well as the site for his orthopedic practice, Orthopaedics Indianapolis. Dr. Farr also serves as a medical advisor and answering doctor for Knee1.com. Dr. Farr was one of the first doctors in the Midwest to perform the Carticel procedure, explained below.
|Carticel is a revolutionary procedure that may save your aching knees. Hear a clip of Dr. Farr describing how Carticel works here:
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Knee1: What trends have you noticed in knee surgery since you began practicing medicine?
Dr. Farr: When I was in my residency, we focused on pathology and treated knee problems in somewhat of an isolated manner. Today, we look at not only the whole knee, but also the whole person presenting with the knee problem. We can now appreciate the interdependence of, for example, the articular cartilage and how it has an influence on the meniscal cartilage. Taken further, we know how the stability of the knee influences both of these cartilages. Furthermore, this interdependency extends to the alignment of the knee and how it effects joint forces which, in turn, affects the viability of the articular and meniscal cartilages. In summary, we are no longer treating isolated knee problems; we are looking at each problem and trying to see how it relates to and affects the rest of the joint. We are using a more holistic approach to the knee. As a result, we are thinking more in terms of a restorative processes, rather than only treating the symptoms of the presentation. The goal is to look for the optimal potential of the joint in the patient’s future and see if there are ways we can maintain the health of the joint.
Knee1: You do a great deal of work with high schools in the Indianapolis area. From talking to other orthopedic surgeons, it seems the level of intensity in high school sports has increased and injuries seem to have become more severe and more common. Has this been the case in your experience?
Dr. Farr: Our experience has been similar in terms of the numbers of injuries, but there are other factors involved. There has been a learning phase that the schools go through. Ten or fifteen years ago, when I started, many of the schools were not as comprehensive in regards to the sports program. They weren't devoted to a year-round program to optimize their athletes. Not all schools had strength coaches and certified athletic trainers. Since there has been a stronger focus on excellence, there is a new commitment to a year-round conditioning and injury prevention programs. With improvements in prevention, strength training and agility, the percentage of injuries appears to have finally begun to diminish–yet with increased participation, I agree the total number of injuries has increased. This coincides with an increase in girls' athletics. Prevention is, fortunately, now the focus.
Knee1: As a consultant to a number of high schools, how do you recommend that students go about their strength training to avoid injury?
Dr. Farr: Strength training is an essential part of every sport. Sport-specific strengthening is a highly developed science. It needs to be performed with a qualified instructor. In the past, the strength-training coach was a secondary position, or someone would just say, "I am going to be the strength coach." Now, schools take this position very seriously and they have individuals who are properly trained in the science of strength training. Schools realize that: first, it needs to be done year-round; secondly, it needs to be done by a professional; and, third, training should be sport-specific. There are whole educational programs, journals and organizations devoted to sports-specific conditioning and pre-season training. These efforts have made great inroads in improving the conditioning of the athlete before they step on the field. This not only improves performance but also appears to decrease injury.
Knee1: You have also done a lot of work with cartilage restoration and transplantation. Could you explain to our readers how you became interested in that field?
Dr. Farr: I became interested in knees when my grandfather needed to have knee replacement surgery but was too old to have it. My father has had knee replacement surgery, and I myself have had knee problems since college football. As you can see, I have had an interest in knees from an early age. When I was starting my practice in 1986, I traveled to Toronto to visit with Alan Gross who is one of the world leaders in cartilage science and surgery. At the time, he and his staff were just beginning some of his now landmark studies on cartilage transplantation. He was doing both basic science work in rabbits and clinical studies with patients. That inspiration drew me back to my background, which was in biological engineering and included some basic lab work in medical school. I have continued to be interested in the basic cartilage science and have kept abreast of developments in the field. When it became clinically relevant, I tried to find ways to take this basic science and apply it to my clinical practice. In 1995, Lars Petersen began training doctors through Genzyme in the Carticel procedure. In Indiana, we tend to be a little more conservative in adopting new trends. Therefore, we are not always at the forefront of new medical developments, so I waited until the FDA approved Carticel in 1997. Once I started Carticel implantation, however, it opened up a whole new way of thinking about the joint. That is, not just trimming and repairing, but preserving and restoring it. Eventually, I was presented with patients that met all the criteria for Carticel implants but did not have a meniscus. Then I needed to learn how to transplant a meniscus. I also had to have precise alignment and with that came osteotomies. These precise osteotomies required led me to the hemi-callotasis technique; as a result, a whole new aspect of my practice developed as it evolved from the desire to begin restoring the articular and meniscal cartilage of the joint.
Knee1: It would be easy for our readers to overlook how far cartilage restoration has come in such a short period of time. Imagine a patient had a lesion in his articular cartilage 10 years ago. Could you explain what their possible treatment options would have been then, and what they are now?
Dr. Farr: In the 1980s, we performed a lot of what was known as abraisionplasty and "drilling." The main thought behind that procedure was that if you stimulated fibrocartilage to grow by drilling into the bone underlying the articular cartilage, you could protect the joint and, hopefully, stop joint degeneration. Unfortunately, fibrocartilage, which is less smooth than native hyaline cartilage, is also not durable. The techniques that we had in the 1980s were gradually refined, but they were still variations on the theme of what we now call "marrow stimulation techniques." These procedures include abraisionplasty, where you scuff up the surface of the bone after the cartilage is removed, drilling, and microfracture, where a small pick is used to make very small fractures. Each of these procedures sought to allow ingrowth of new healing cells from the blood supply and bone marrow. All of these techniques form fibrocartilage. That continued as the state of the art into the 1990s. At that time, research institutions that were pioneering work with autologous cultured chondrocyte implantation and fresh allograft (donor tissue) osteochondral shells (implants including both bone and cartilage). However, at that time, those techniques were not available to the general orthopedic community. A patient in the local community would have been limited to standard clean up (shaving, for example), or marrow stimulation techniques. These limitations are no longer present.
Knee1: Now, the same patient may undergo the autologous chondrocyte implantation procedure, otherwise known as ACI or Carticel. Can you explain how this procedure works?
Dr. Farr: At the present time, we are still doing what we will termed in the future "Carticel One," which is an outgrowth of the research that Lars Petersen performed more than 10 years ago in Sweden. This involves a knee surgeon taking a small sample of articular cartilage from an area that has minimum weight-bearing responsibilities in the joint. The sample, about the size of two Tic-Tacs, is transferred to a laboratory where the biopsy is removed and then cultured. Articular cartilage, which covers the ends of the bones, doesn't appear to be alive; it appears to be a rubber- or plastic-like structure. It is, however, 5 percent living cells—the chondrocytes. The cells are grown in a culturing process, in which the sample, again, about the size of two Tic-Tacs, or about 200,000 to 300,000 cells, in multiplied through cell culturing to about 11 to 12 million cells. The culture chondrocytes are then sent back to the implanting surgeon. The surgeon then implants the cells into the defect under a covering of periostuem, which not only keeps them in place but also supplies growth factors and allows nourishment to pass to the cells from the joint fluid. (Periosteum is the thin fibrous tissue that covers long bones).
Knee1: You mentioned that this procedure is "Carticel One." What is on the horizon for ACI in Carticel Two?
Dr. Farr: The goals of patients and surgeons alike are similar: that is, to make any procedure less painful, involve less rehabilitation and to have the procedure performed with potentially a smaller incision. We are looking for a minimally invasive way to implant Carticel. One of the options is to have a substrate on which the cells are already implanted. The substrate may then be cut or formed to fit the defect, rather than using periosteum. This procedure will allow a less-invasive approach, and potentially involve one less incision from the periosteum-harvesting site. It will also make the operation potentially quicker, and, thus, possibly more comfortable for the patient during recovery.
Knee1: Who is at the greatest risk for articular cartilage injury?
Dr. Farr: Anyone who walks around on two feet (laughs). The more stress to the joint, the higher the risk. Stress can occur with sports, work or activities of daily living. One of the problems in recognizing articular cartilage injury is that the symptoms mimic the symptoms of other injuries. As a result, the clinical impression is often that the patient has only torn their meniscus, and yet arthroscopy may show that it is an articular cartilage lesion. The classic symptoms of pain: swelling, and mechanical sensations like locking or catching, can result from injury to both the articular cartilage or meniscal cartilage. These symptoms are somewhat nonspecific. It is very difficult clinically to separate the two. Any type of trauma to the joint that can injure the meniscus or a ligament can certainly injure the articular cartilage. For example, it is becoming more appreciated that patients who have patellar dislocations will have an injury to the articular cartilage, and patients who have an anterior cruciate ligament tear are prone to articular cartilage injuries as well as meniscal tears. With each of these major injuries, the surgeon needs to look for and define the extent of articular cartilage injury.
Knee1: In a foreword for the upcoming journal article you wrote with Dr. Brian Cole, you mentioned that, just as all total knee replacement recipients do not always need the highest state-of-the art (and therefore most expensive) artificial knee, patients who undergo cartilage restoration may benefit differently from different surgeries. Do you think the procedure will someday be adaptable to the patient's specific needs?
Dr. Farr: The concept that we have borrowed from the total joint surgeons is one of demand matching. We would like to match each cartilage restoration surgery to each patient's needs. It is obvious that there are only finite resources for knee health care in the world. To suggest the most expensive surgery is the best option in each case is not reasonable. What we would like to do is be able to match the appropriate type of articular cartilage surgery to the individual patient's requirements. For example, a small lesion in an older, less-active patient will potentially do well with a marrow-stimulation technique. That procedure will obviously form fibrocartilage, but fibrocartilage may be appropriate for this type of lesion. On the other hand, a younger, higher-demand patient with a large lesion probably needs the closest thing we can offer to native hyaline cartilage. Said in another way, we are trying to match the treatment to the problem.
Knee1: You are also working on an alternative meniscus-transplant system with Regeneration Technologies [link]. Can you tell us more about that work?
Dr. Farr: We are now working with the meniscus transplantation instrument prototypes. They should be available for surgeons within the next few months. There are basically three ways to insert and fix a meniscus transplant: the first way is to do a soft tissue repair, the second way is to attach bone plugs at the horns, and the third way is to have a bone bridge.
Knee1: Could you explain the difference between the three?
Dr. Farr: Think of the meniscus as a half-moon shaped piece of tissue that looks a bit like a bucket handle. With a soft tissue repair, the surgeon stitches the meniscal transplant sutures to the soft tissues and bone. With a bone-plug technique, you attach plugs of bone to the pivot points of the bucket handle, anchoring the plugs into holes in the bone. That procedure makes for nice, firm, bony anchoring of the meniscus, which is attached by its own fibers to the plugs. The advantage of bone plugs is the firm, rigid fixation. The disadvantage, however, is that the surgeon has to place the bone plugs in the recipient's tibia at the proper distance from one another. If the surgeon is off one millimeter or two at the front or the back, the error could potentially effect the reduplication of the function of the meniscus. The bone bridge is a portion of bone (from the transplant) that connects the anterior (front) horn to the posterior (rear) horn. The connection assures that the relation, or distance, between the two horns is maintained. When the surgeon places this entire bridge into the proper position there is thus one less measurement that has to be taken into account, that is, there is potential for a more anatomic fit.
Knee1: What studies have been done on the three approaches?
Dr. Farr: A couple of recent studies in the past year or two have shown that a soft tissue repair alone does not duplicate the function of a normal meniscus, as far as transferring the load and improving contact surface area. There is an improvement of about 50 percent with bone plugs. Those studies did not investigate the bone bridge technique. Empirically, it would appear that the bone bridge, by maintaining the true dimensions between the anterior and posterior horn, should maintain at least the characteristics of the plugs and possibly be more accurate. It would appear, then (and we are making a leap of faith without much clinical data yet), that a bone bridge would possibly more closely mimic the function of a natural meniscus if implanted correctly. Research will shed needed light on this subject.
Knee1: You are also looking into custom-shaped allografts, or grafts from donors. Tell me about your work with that.
Dr. Farr: The technique involves implanting custom-fit, live articular cartilage (with a thin underlying bony shell) into a severely damaged knee. This is based upon the pioneering work of Gross, Meyers and Garrett. The attachment of the osteochondral shell allograft to the host is known as "creeping substitution," because the body's own bone grows into the implant and gradually “makes it as its own”. It is a very slow process; it may take as long as several months for some specimens; for others, it may take as long as two years. During that period, the site has to be protected to allow the graft bone to mature as it is “substituted”; otherwise the implant may collapse.
Custom-shaped allografts are a technique for transplantation of articular cartilage, which was performed at the above surgeon’s institutions where they had access to fresh tissues that were rapidly implanted to maintain the viability of the articular cartilage. Tissue labs now have a technique that nourishes cartilage. This is possible without a blood supply using a special fluid, because the native articular cartilage receives its nutrition from the joint (synovial) fluid, not from blood. Studies have shown that up to 80 percent of the articular cells may remain viable up to six weeks after removal. Thus, we now have a longer window for both transport to a surgeon and evaluation of the donor tissue. This evaluation period allows the opportunity to perform an autopsy and develop a medical history of the donor (to make sure that they were not at risk for certain types of infection). Time is also available to run extensive blood tests for both antibodies and antigens of infectious agents. With those important factors, the probability of disease transmission to the recipient is markedly diminished. We must keep in mind that the donor's articular cells have to remain viable. If they aren't viable, then the long-term viability of the implant is compromised. As a result, when I have implanted these types of allografts, I have tried whenever possible to determine the viability of the implant. This is a technique in which we are methodically slowly progressing, so that we can follow patient outcomes closely.
Knee1: We have come a long way in the past 10 years with cartilage restoration. What direction do you see it taking in the next 10 years?
Dr. Farr: I think that tissue engineering will expand rapidly. Microenvironment (growth and genetic) engineering will be important, as well. The end goal is to restore a pain-free, fully functional joint with the least invasive means possible. In the next few years this may be through manipulation of plural-potential stem cells. These cells may be transformed into articular cartilage and then stop their transformation and remain as viable chondrocytes, generating healthy normal hyaline cartilage. That transformation will probably require a specifically timed cocktail of genetic and local environmental factors. One of the potential uses of this technology may actually come about by modifying the marrow-stimulation techniques developed 10 to 15 years ago by using newly developed ways to manipulate these cells. Orthopedics, in general, constantly builds upon past techniques and cartilage may be another example. I look forward to these exciting times in cartilage restoration.
Photo courtesy of Dr. Jack Farr.
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