I wrote this paper for EPD 397 (Technical Communications) in the Fall 2000 semester. The paper has recently been chosen for publication in the Undergraduate Engineering Review, an online journal that publishes the best papers submitted by instructors of EPD 397. If you'd like to read a quick summary of my paper, see my Executive Summary.
J. Bern Jordan
Biomedical Engineering Department
University of Wisconsin at Madison
June 17, 2001
The healthy human knee joint is lined with articular cartilage: a layer of tissue that provides low-friction and shock-absorbing properties. Arthritis and injury can damage this protective layer of cartilage, causing extreme pain for a patient performing even simple activities. This report compares four available treatments for these patients: total knee replacement, unicompartmental knee replacement, viscosupplementation, and autologous chondrocyte implantation. The cost, service life, and complications associated with each procedure are evaluated. A physician must carefully consider these procedural differences and the patient's specific situation when deciding on a particular course of treatment.
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In a healthy human knee, the joint surfaces are lined with articular cartilage that provides low-friction and shock-absorbing properties. Through arthritis and injury, the cartilage may become damaged--either worn away or torn. In severe cases, the loss of this cartilage cushion causes debilitating pain and prevents patients from performing simple, everyday activities.
This report describes and compares four treatment options for patients with damaged knee cartilage: total knee replacement, unicompartmental knee replacement, viscosupplementation, and autologous chondrocyte implantation (ACI). A total knee replacement is implanted by an orthopedic surgeon to replace the articular surfaces of the knee bones. For patients with damage isolated on one side of their knees, a unicompartmental knee replacement, also known as a partial knee replacement, may be performed. Viscosupplementation is an injection for the knee that helps to lubricate the joint, thus lessening friction and pain. Granted accelerated approval by the FDA in 1997, ACI is an unproven yet promising procedure. For ACI, the knee surface is repaired with cartilage grown from a patient's own healthy tissue. Each of the reviewed procedures has strengths and weaknesses that make it appropriate for some patients and not others.
Viscosupplementation is the least expensive procedure reviewed because it does not require surgery. Unfortunately, a treatment with a viscosupplement lasts for a year at most compared to the 10 to 15 year service life of a total knee replacement. The surgeries involved with ACI and both total and unicompartmental knee replacements increase the risk of complications. ACI has great potential, but only for patients with localized defects in the femoral cartilage. Of the two knee replacement procedures, the unicompartmental knee replacement is safer and less invasive. However, because a partial knee replacement mends only one side of the knee, it is not as versatile as a total knee replacement.
There is not a single, standout treatment for patients with damaged knee cartilage. When deciding on the proper treatment, one must consider the patient's activity level, age, and history. Depending on the situation, one of the treatments may be an obvious choice, or the physician and patient may have to decide which one is best. In the future after more research, the physician will have more options from which to choose.
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Throughout a day, the knee joint undergoes a wide range of motion and stress. In a healthy knee, the articulation* between the bones of the knee is lined with cartilage. This cartilage serves to keep the knee stable, reduce joint friction, and absorb shock. Serious problems result when this cartilage deteriorates--in some cases, a patient may be in so much pain that he or she cannot walk.
There are many causes of the loss of this cartilage cushion. Traumatic injury and high impact activities can damage the cartilage directly (e.g. a piece of cartilage breaking off) or indirectly through arthritis. Osteoarthritis, currently affecting an estimated 20.7 million Americans ["Osteoarthritis," 2000], is characterized by joint cartilage breakdown, especially in the hands and weight-bearing joints. Rheumatoid arthritis is an autoimmune disease where the body's defense mechanism attacks the healthy joint tissue. Genetic defects can also predispose a person to having knee problems.
Depending upon the amount of joint damage, there are different treatment options available. For mild cartilage damage, it is sufficient for a patient to adjust his or her lifestyle by wearing a brace or performing therapeutic exercises. With more extensive cartilage damage, it is necessary to perform surgery to resurface the cartilage and remove broken pieces in the knee. For the most severe cases such as bone grinding against bone, it may be necessary to replace the joint surfaces.
The National Center for Health Statistics reports that over 250,000 people nationwide annually undergo total knee replacement [Popovic & Kozak, 2000]. Generally, total knee replacements are successful, but problems such as infection and prosthetic loosening can arise with this procedure. Even after a successful knee replacement, the patient should be careful with his or her knee and should not run or play vigorous sports. Total knee replacements are not recommended for younger patients because the prostheses last for only about 10 to 15 years with low activity levels.
The purpose of this report is to compare four available treatment options for patients with severely damaged articular knee cartilage. Two of the reviewed treatments, total knee replacement and unicompartmental knee replacement, are replacements or prostheses for the knee joint. The two other reviewed treatments, viscosupplementation and autologous chondrocyte implantation, have been approved by the Food and Drug Administration (FDA) within the past four years.
The first section of the report provides the medical and anatomical background necessary for this report. In the following section, each of the four treatments is described including the required surgical procedures and the graft and devices themselves. This section also lists some of the indications (the circumstances when a treatment may be performed) and contraindications (specific situations when a treatment may not be used) associated with each treatment. Finally, the costs, service lives, and complications involved with the four treatment options are compared. This report concludes with general recommendations and a quick overview of the future of knee treatments.
*All emphasized and hyperlinked terms may be found in the Glossary.
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The knee is not a simple hinge or pivot joint; when one walks, the surfaces of the knee roll and slide against each other. With every step, the knee experiences compressive forces several times that of the body weight.
The knee joint is comprised of several bones, which can be seen in Figure 1. Two bones, the femur and tibia, bear the weight of the body while the patella and fibula provide support and allow for greater mobility. The thighbone, or femur, is the longest and strongest bone in the human body. Articulating with the femur is the tibia, or shinbone, which is located at the front of the leg and serves as the weight-bearing bone of the lower leg. For protection, the articulation between these two long bones is covered in a shock-absorbing, low-friction layer of articular cartilage. The patella, commonly known as the kneecap, is a small, triangular, disc-like bone that sits at the front of the knee. This bone protects the knee joint and provides leverage for the muscles of the leg. The fibula is a long slender bone located laterally and posteriorly to the tibia. It is not a part of the knee joint itself; instead, it articulates with the tibia and helps to stabilize the ankle and acts as an anchor for muscle attachment.
A fibrous tissue capsule surrounds the knee joint. Depending on a person's activity level, the knee capsule contains 0.3 to 1 mL of synovial fluid [Baumgarten, et al., 1985]. The viscous synovial fluid serves multiple purposes. It acts as a lubricant to reduce friction between the knee joint surfaces much like motor oil lubricates engine components. It also behaves like a shock absorber by distributing stresses in the joint due to impact and motion. Finally, synovial fluid serves as a transport medium by removing waste and carrying nutrients to the articular cartilage.
Articular cartilage is a specialized form of cartilage that reduces joint friction, resists wear, and distributes forces to the underlying bone. The cartilage has a specialized structure with a relatively hard outer surface of collagen fibers on an underlying porous collagen structure. This structure allows the cartilage to have a wear-resistant surface on a flexible, shock-absorbing substrate. The cartilage of the knee is living tissue but is avascular and thus does not have its own blood supply. It receives all of its nutrients from the surrounding synovial fluid. Once damaged through arthritis or injury, articular cartilage has limited regenerative capability.
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This section provides a brief overview of each procedure; however, treatment details may vary depending upon the surgeon and specific case. In all cases, physical therapy is recommended to help the patient maintain muscle for knee strength and stability. Three of the four treatments require surgical procedures for implantation and some physicians recommend the use of a brace or cane after surgery.
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A total knee replacement is a resurfacing of a patient's knee joint. Older types of knee replacements were modeled after hinges, but today's total knee replacement prostheses duplicate the anatomy of the knee joint to allow for more natural motion. The orthopedic surgeon can choose from a variety of total knee replacement models depending upon the patient. For example, some knee replacement prostheses are large to replace a significant amount of lost bone while others are made to save the ligaments of the knee.
A typical total knee replacement prosthesis consists of three components: a femoral component, a tibial component, and a replacement for the posterior patellar surface. The femoral component is generally made of non-corrosive metal (most frequently a cobalt-chrome alloy), although some are made of ceramic. The tibial component is a metal tray topped by a spacer of a special plastic known as ultrahigh molecular weight polyethylene (UHMWPE). UHMWPE exhibits relatively low friction in a metal-plastic joint and resists wear better than many older alternative materials [Unsworth, 1991]. The last component is a replacement for the posterior surface of the patella for articulation with the other components. Figure 2 shows the femoral and tibial components of a representative knee prosthesis.
Before the surgical procedure, one should make several preoperative visits with an orthopedist and physical therapist. These doctors help to prepare the patient for the surgery and postoperative changes. Also during these preoperative visits, many patients donate their own blood because transfusions are frequently required.
The orthopedic surgeon makes a seven- to ten-inch long incision to access the damaged knee joint. Specialized jigs, or resection guides, are used to guide the surgeon when removing the bone of the knee. The knee joint ends of the femur and tibia are sawn off to make a level surface for the attachment of the prosthesis. The prosthesis may be affixed to the bone with a cement such as poly(methyl methacrylate), or an uncemented prosthesis may be used. An uncemented prosthesis has a porous surface into which the bone grows, thus holding it in place. Figure 3 shows x-rays of a knee replaced with a total knee prosthesis.
The total knee replacement can be used for many patients. People with osteoarthritis, rheumatoid arthritis, or other degenerative joint diseases and defects can all be successfully treated.
Two-thirds of those who undergo a total knee replacement are over 65 years of age [Popovic & Kozak, 2000]. Many orthopedists are hesitant to recommend the procedure for young individuals because the components last for only 10 to 15 years. Total knee replacements are not recommended for patients that are morbidly obese because the weight can cause the prosthesis to wear faster.
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A unicompartmental knee replacement, also known as a partial knee replacement, involves a procedure similar to that used to implant a total knee replacement. Instead of replacing the entire knee, the unicompartmental prosthesis replaces one condyle, or side, of the knee joint. Figure 4 shows a diagram of a unicompartmental prosthesis in place.
Because a unicompartmental prosthesis replaces one side of the knee, the surgeon does not have to make as large an incision as for a total knee replacement. To access the side of the knee, the surgeon makes a three-inch incision. This smaller incision decreases the risk of complications and the loss of blood. Because of this, most patients do not need a blood transfusion during the surgery.
After opening the knee, the surgeon removes the damaged side of the knee with a bone saw and resection guides. The prosthesis is then cemented into place and the wound is closed. By implanting a unicompartmental knee replacement, the surgeon can save more ligaments and bone compared to a total knee replacement.
This procedure is only recommended for patients with cartilage damage limited to one condyle. The other side of a candidate's knee should be relatively healthy; otherwise it would be more sensible to perform a total knee replacement.
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Viscosupplementation is the injection of a fluid to supplement or replace the natural synovial fluid in the knee joint capsule. In many osteoarthritic knees, the synovial fluid is less viscous and less elastic than that found in healthy knees [LaPrade & Swiontkowski, 1999]. The injection affords more lubrication and cushioning for the articular cartilage in arthritic patients.
Most viscosupplements contain hyaluronan (a high-molecular weight molecule comprised of repeating monosaccharide units) or hyaluronan derivatives. Synovial fluid naturally contains hyaluronan, but the synovial fluid of arthritic knees is thinner because of changes in the hyaluronan [Baumgarten, et al., 1985]. Molecules of hyaluronan are large and become entangled in the synovial fluid of the knee. The entanglement of these large molecules is what provides the synovial fluid's viscous and shock-absorbing properties ["Classroom," 2000]. There are several viscosupplement injections on the market in the United States including Hyalgan® produced by Sanofi-Synthelabo U.S., Supartz® by Smith & Nephew, Orthovisc® by Anika Therapeutics, and Synvisc® by Genzyme Biosurgery.
Synvisc® (Hylan G-F 20) is a prescription viscosupplement manufactured by Genzyme Biosurgery and distributed in the United States by Wyeth-Ayerst Pharmaceuticals. Synvisc is manufactured using the hyaluronan extracted from chicken combs ["Synvisc," 2000]. Because Synvisc works by physical action (elastoviscosity) and not by chemical action, it is classified by the FDA as a device rather than a drug.
Synvisc is sold in the United States in syringes that contain 2 mL of the viscosupplement. It is not necessary to visit an orthopedist to get injections of Synvisc; many physicians are qualified for the procedure. Three injections, on Day 1, Day 8, and Day 15, constitute a Synvisc treatment cycle.
The procedure for injecting Synvisc is simple. The physician first cleans the skin near the injection site and aspirates or removes the synovial fluid in the knee joint using an 18- to 25-gauge needle. Using the same needle, the physician then injects the Synvisc viscosupplement. The procedure can be performed on both knees during the same visit. Most patients show the best response 8 to 12 weeks after the three-injection treatment cycle.
Synvisc is recommended for patients with mild to moderate osteoarthritis who have not seen much success with conservative treatments. Viscosupplementation does not provide as much benefit for patients with advanced osteoarthritis [LaPrade & Swiontkowski, 1999]. Wyeth-Ayerst reports that 58% of patients with severe cartilage damage exhibited some improvement with Synvisc. For patients with mild to moderate osteoarthritis, 91% reported improvement [Wyeth-Ayerst, 2000].
According to the manufacturer, Synvisc should not be used for patients with allergies to hyaluronan preparations or infections of the knee joint ["Synvisc," 2000]. Synvisc has only been approved for treating patients with osteoarthritis. Also, the manufacturer has not determined the effectiveness and safety of multiple treatment cycles.
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Autologous tissue is tissue that has been donated for one's own future procedure. In this case, chondrocyte cells (cells that make cartilage) are harvested from a healthy portion of the knee and are grown in vitro. The cultured cells are then used to repair defects in the articular cartilage of the knee.
Genzyme Biosurgery, a division of the Genzyme Corporation, produces a product in the United States called Carticel®. The FDA granted accelerated approval for Carticel in 1997 ["FDA," 1997]. Between 1995 (when Carticel was first marketed in the United States) and early 2000, nearly 4,000 Americans were treated with Carticel autologous chondrocytes ["Carticel," 2001].
To obtain chondrocyte cells for the procedure, the surgeon first performs an arthroscopic biopsy and removes some of the patient's healthy cartilage from a non-weight bearing portion of the femur. These harvested cells are sent to Genzyme Biosurgery's processing facility in Cambridge, Massachusetts. The cells are then cultured for three to four weeks, and the autologous cells are shipped in a vial that contains approximately 12 million chondrocytes ["Carticel Package," 2000].
The second surgery, the implantation of the chondrocytes, is performed after the cultured cells are received from Genzyme Biosurgery. First, the surgeon makes a six- to eight-inch incision in the knee and flexes it to expose the defect. The edges of the defective cartilage are cut away, or debrided, to leave vertical margins around the area of the defect. See Figure 5 for a drawing of the femoral cartilage before and after debridement.
The surgeon measures the size of the debrided defect and creates a slightly oversized template. A second incision is then made just below the knee. Using the template as a guide, the surgeon removes a graft of periosteal tissue from the medial side of the tibia. This periosteal graft is trimmed and then sutured to the articular cartilage. A small portion at the top of the graft is not sutured to allow for the injection of the autologous cells. As can be seen in Figure 6, the periosteal graft acts as a cover over the defect.
Using a saline solution and a syringe, the surgeon tests the periosteal graft to ensure that it is watertight. If the graft leaks, stitches are added to close the gaps. Once graft integrity is ensured, a sealant is applied around the borders of the graft (the opening at the top of the periosteal graft is left unsealed). The Carticel preparation is prepared by mixing the cells and the cell medium and is then injected underneath the periosteal graft through the opening left by the surgeon. Finally, the periosteal graft suture is completed and sealed.
After the surgical procedure, the patient must use crutches to avoid bearing weight on the knee. A physical therapist helps the patient regain muscle strength and range of motion in the joint. It may take up to a year before a patient may resume all activities.
Carticel has only been approved for repairing defects of the femoral articular cartilage ["Carticel Package," 2000]. These defects must be focal or localized defects in the articular cartilage; the procedure is not useful for widespread cartilage damage or for the treatment of osteoarthritis [Illgen, 2000].
Genzyme recommends against using Carticel for patients sensitive to bovine serum or gentimicin ["Carticel Package," 2000]. These substances are used when the autologous chondrocytes are cultured.
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When deciding on a particular treatment, a physician must understand a patient's needs and the differences between treatments. The four reviewed treatments differ widely in cost, service life, and associated complications.
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The costs associated with each procedure vary widely. The physician, the area in which one lives, and the type of prosthesis or device chosen all have an effect on a treatment's cost. As an example of this, Genzyme reports that the price of the Carticel graft and procedure is between $17,000 and $38,000 ["Carticel Autologous," 2000]. Each of the four treatments involves several visits with a physician and sometimes follow-up visits with a physical therapist. Table 1 lists the average cost and range of costs for the required procedures.
|Range of costs for entire procedure||Average cost for entire procedure||Cost for device or graft|
|Total knee replacement||$8,000-$30,000||$16,000||$1,000-$4,000|
|Unicompartmental knee replacement||$6,000-$22,000||$11,000||$700-$2,000|
|$750-$1,000||$800||$700 for three vials|
|Carticel® autologous chondrocyte implantation
["Carticel Autologous," 2000]
Viscosupplementation is the least expensive treatment option for two major reasons: the device itself is relatively inexpensive and the procedure is simple with no required hospital stay. The other three treatments involve surgery and are expensive because of the complexity of the procedure and hospital stay. A unicompartmental knee replacement is a less expensive procedure than a total knee replacement because it is quicker and less invasive. Finally, autologous chondrocyte implantation is the most expensive treatment because it requires two procedures and special culturing techniques for the chondrocytes.
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Total knee replacements are expected to last 10 to 15 years in older patients. Unicompartmental knee replacements tend to loosen earlier, after 7 to 12 years, because they are smaller and cannot be cemented as well as total knee replacement prostheses [Vanderby, 2001]. Once a knee replacement fails, a revision surgery is performed. A knee replacement revision is a more involved procedure than the initial joint replacement, because it requires a new incision and the removal of more bone.
The service life of a knee replacement depends greatly on the activity level of the patient. A knee replacement would likely need an earlier revision with younger or more active patients. An early revision is cause for more concern because a patient must then spend a longer time with the revision prosthesis [Illgen, 2000].
The metal used for knee replacements is durable, but the ultrahigh molecular weight polyethylene (UHMWPE) spacer of the tibial component wears with use. The UHMWPE spacer can be replaced, a procedure known as a retread, if the rest of the knee replacement is still sound. However, the main method of knee replacement failure is the loosening of the components. With use, all knee replacement components will gradually loosen and become detached from the bone.
Viscosupplementation is a temporary solution for osteoarthritis because a treatment lasts for 6 to 12 months depending on a patient's lifestyle [Wyeth-Ayerst, 2000]. The hyaluronan and other molecular components of the viscosupplement are eventually absorbed by the lymphatic system. The use of Synvisc for more than one treatment cycle of three injections has not been approved in the United States ["Synvisc," 2000]. However, some physicians perform multiple treatment cycles based on information from European trials [Wyeth-Ayerst, 2000].
Autologous chondrocyte implantation is a new procedure, so the long-term results are unclear. Clinical follow-ups performed for a Swedish study show promising results up to ten years after the chondrocyte implantation [Peterson, 1999]. However, the long-term studies of chondrocyte implantation have been small with relatively few patients. Because of this uncertainty, the American Academy of Orthopaedic Surgeons suggests that orthopedists use caution when recommending this procedure for patients [Buckwalter, 1996]. The ability of a chondrocyte transplant procedure to provide long-term articular cartilage has not been established [Bobic & Noble, 2000], but generally autologous chondrocyte implantation is viewed as a better option than a total knee replacement for young patients that meet the clinical indications. The implant acts as a more natural cartilage replacement and will not loosen like a knee replacement.
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Both knee replacement and chondrocyte implantation require a surgeon to make an incision and open up the knee. There are many complications associated with such surgeries. Anesthesiologists are careful to screen patients before using an anesthetic, but occasionally a patient may have a severe reaction. For any surgery, there is a risk of vascular or nervous tissue damage. There is also a chance of infection even though surgery is performed under aseptic conditions. Deep venous thrombosis, the formation of blood clots in large veins, can occur after a knee surgery. If a clot breaks apart, it may travel to and become lodged in lung capillaries, a condition known as pulmonary embolism. To minimize the risks of a pulmonary embolism, many patients are prescribed blood thinners and pressure stockings to keep blood moving. Surgical complications occur less frequently during less invasive procedures.
In the long term, both metal and UHMWPE wear debris from the artificial joint accumulates in a patient's joint tissue, lymph nodes, liver, and spleen [Urban, et al., 2000]. This debris has not been proven hazardous to a patient's health, but the wear debris can cause the knee capsule to become inflamed. The inflammation can then lead to osteolysis and prosthetic loosening.
Post-surgical infection of the knee can be a problem for patients with knee replacements. The prosthesis is inert, so it has no disease fighting capabilities. The surface of the implant also serves as the ideal site for colonization by pathogens [Gristina & Naylor, 1996]. A patient with a knee replacement should take antibiotics before any dental work or invasive procedure to minimize the chances of infection.
Autologous chondrocyte implantation is a relatively new procedure, so the complications associated with the procedure are unclear. The most common complication reported is tissue hypertrophy ["Carticel Package," 2000]. With tissue hypertrophy, the cartilage continues to grow outside the original graft and can form a ridge of excess tissue. This condition can generally be corrected through arthroscopic surgery.
There are few complications associated with viscosupplementation because of the simple, non-invasive procedure. The most frequently occurring adverse effects after treatment are knee pain and stiffness ["Synvisc," 2000]. Some adverse effects may be attributed to incorrectly placed injections [Jones, et al., 1993].
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For many patients, the pain of worn knee cartilage and arthritis is debilitating and prevents them from performing basic activities. The four reviewed treatments promise to increase the patient's quality of life--allowing him or her to walk with less pain.
The choice of treatments is complex and is best made with a physician's advice. A physician will be able to provide information for a patient's specific condition and help the patient weigh his or her options. As an example, a physician may recommend a unicompartmental knee replacement for a middle-aged patient with a severe varus deformity (also commonly known as "bowed legs"). The cartilage of the medial portion of such a patient's knee could be worn so that bone would painfully grind against bone. The unicompartmental replacement procedure would remove less bone and would be less invasive than a total replacement. However, if the lateral portion of the knee was also damaged through osteoarthritis or if the patient were elderly, the physician may instead choose to implant a total knee replacement.
Viscosupplementation is an inexpensive treatment for osteoarthritis. Unfortunately, it is a temporary solution and has not been approved for multiple treatment cycles once the symptoms of osteoarthritis reoccur. This treatment seems to be useful in delaying a more invasive procedure for up to a year.
Autologous chondrocyte implantation is a promising treatment, but the long-term effectiveness is unknown. Regrowing one's own cartilage seems to be the ideal solution, but it can only be used for small defects in specific areas of the femoral cartilage. The expense and length of time required for cartilage regrowth make this option less attractive, especially for elderly patients. While unproven in the long term, this procedure seems best for young patients that meet the clinical indications. It does not require the removal of bone and can be revised easily if it fails.
A total knee replacement is irreversible yet versatile. Patients with many different knee problems can be helped with a knee replacement. For older patients, the components may last a lifetime; however, once a patient has a total knee replacement, a full revision is the only option in case of failure. If the other three treatments fail, then there are still other available treatments (including a total knee replacement if necessary). For middle-aged and younger people, a total knee replacement should be one of the last procedures to consider. Even though most knee replacements last over a decade, they are still an inferior substitute for one's natural joint.
Researchers are working in many directions to design new knee treatments and improve old treatments. Improving the materials used in a knee replacement could make it more wear-resistant and cause less debris buildup in tissues. Research is currently being performed to understand chemical signaling and the host response to implants. As a result of the research, gene therapy or chemical signal drugs could be used to prevent an immune reaction to an implant or could signal chondrocyte cells to multiply [Vanderby, 2001]. Tissue engineers are taking an approach similar to autologous chondrocyte implantation by letting the body repair itself. In the future, a physician could implant in a defect a functional replacement scaffold with chondrocyte cells. This scaffolding could be absorbed by the body as the chondrocytes grow to replace the lost cartilage.
It is important for an individual to do all one can to take care of his or her knees because the currently available options are inferior to the natural healthy knee joint. For those individuals that have injuries, wear, and arthritis of the knee, the treatments promise to restore some of the normal knee function. With the proper treatment, a patient can walk with less pain and discomfort.
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