THIS PATIENT INFORMATION BROCHURE IS PROVIDED TO US FROM GENZYME BIOSURGERY MAKERS OF THE CARTICEL SYSTEM

For the Repair of Articular Cartilage Injuries of the Knee

Carticel® (autologous cultured chondrocytes), marketed in the United States and Europe by Genzyme Biosurgery, employs a commercial process to culture a patient's own (autologous) cartilage cells, known as chondrocytes, for use in the repair of symptomatic cartilage defects of the femoral condyle (medial, lateral, or trochlear) caused by acute or repetitive trauma in patients who have had an inadequate response to a prior arthroscopic or other surgical repair procedure. It is not indicated as a treatment for people suffering from osteoarthritis. It is not recommended for use in patients with a known history of allergy to the antibiotic gentamicin, in patients with sensitivities to materials of bovine origin, who have an unstable knee, or who have an abnormal weight distribution within the joint. Patients who have previously had cancer in the bones, cartilage, fat or muscle of the treated limb should also not be treated with Carticel. Any instability of the knee or malalignment of the joint should be corrected before or concurrent with Carticel implantation. Use in children, or in joints other than the knee has not yet been assessed. Data regarding outcomes beyond 3 years are limited. The most frequently reported adverse events are: hypertrophic tissue at the repair site, intra-articular adhesions, superficial wound infection, hypertrophic synovitis, and post-operative hematoma. See accompanying package insert for additional information on warnings, precautions and adverse events.

Once damaged, joint cartilage does not normally regenerate in the body. In addition to causing pain and restricted mobility, chronic injuries to joint cartilage over time may lead to further deterioration of the joint surface. These manifestations can severely hinder a person's normal activities and occupation.

Some people undergo arthroscopic surgery to smooth the surface of the damaged cartilage area. Other surgical procedures, such as microfracture, drilling, and abrasion, may provide symptomatic relief, but the benefit usually is temporary, especially if the person's pre-injury activity level is maintained. These procedures are performed with the intent of allowing bone marrow cells to infiltrate the defect, resulting in the formation of a fibrous cartilage tissue, which is less durable and resilient than normal articular cartilage.

More severe and chronic forms of knee cartilage damage can lead to greater deterioration of the joint cartilage and may eventually lead to some of the many total knee joint replacements performed each year. Approximately 200,000 total knee replacement operations are performed annually. The artificial joint generally lasts only 10 to 15 years and is therefore not recommended for people under the age of 50 (consult your doctor about this option).

An Option for Patients

The technique of autologous cultured chondrocytes implantation was initially researched at the Hospital for Joint Diseases in New York and further developed at the University of Gothenburg and Sahlgrënska University Hospital, Gothenburg, Sweden, in an effort to provide a treatment option for people with joint cartilage damage. Carticel is used in people who are experienceing knee pain as a result of an inadequate response to a prior arthroscopic or other cartilage repair procedure. Patients with this type of cartilage damage also display symptoms that include locking, catching, localized pain and swelling.

Carticel Procedure

The procedure starts when a trained orthopedic surgeon provides Genzyme Biosurgery with a biopsy of healthy knee cartilage, about the size of a raisin, from the patient during an arthroscopic procedure. Technicians at the company's FDA licensed cell processing facility in Cambridge, Mass., use proprietary methods to grow millions of new cells for that patient. The cells are then delivered in a vial to the surgeon who implants them into the defect in a surgical repair procedure. During surgery, the physician carefully removes damaged tissue and prepares the defect for the introduction of the cultured cells. A small piece of the periosteum, the tissue covering a bone, is taken from the patient's lower leg and sutured over the defect like a patch to hold the cells in place. The cultured cells are then implanted under the periosteum in the defect where they can fill the defect with a durable cartilage. Most patients are back to full weight bearing within 6-8 weeks and resume physical activity within one year.As of March 31, 2000, 3,952 patients had been treated since Genzyme began marketing the product in 1995. There are 136 million people covered by insurance plans that pay for Carticel® (autologous cultured chondrocytes) as a matter of policy in the United States.Today Carticel® is considered a viable treatment option and most healthcare plans now reimburse fully for appropriate patients - check with your health care administrator where you work for more details or contact us at Genzyme Biosurgery.

The Surgery

Carticel® (autologous cultured chondrocytes) is one of the exciting treatment options that has demonstrated important benefits to patients with specific types of cartilage defects on the end of the thigh bone or femur. Carticel provides surgeons with a "biologic option" to treat patients who have failed to receive or obtain symptomatic pain relief from a previous surgical repair procedure.

Step 1: Biopsy Your surgeon takes a tiny piece of healthy cartilage during an arthroscopic procedure.
Step 2: Biopsy Processing and Cell Culturing The biopsy is sent to Genzyme Biosurgery in Cambridge, Massachusetts, for processing and culturing. Processing releases the chondrocytes which are then cultured or grown for about 5 weeks. The chondrocytes multiply significantly, yielding about 12 million cells. These cells, Carticel, are returned to your surgeon for implantation.
Step 3: Incision An incision is made to expose the injury and damaged cartilage is removed.
Step 4: Periosteum Harvest and Suture Periosteum, a tissue that covers the bone, is harvested from the shin bone and sutured over the injury site to create a water tight compartment ("patch").
Step 5: Implantation After ensuring that the injury site is water tight, Carticel is implanted beneath the periosteum. Here the cells may continue to multiply, forming the building blocks of healthy cartilage and integrating with surrounding cartilage. With time, the cells will mature and fill in the injury site with a firm, durable tissue.

Frequently asked Questions about Carticel

Will I need physical therapy following this surgery?

Yes. All patients undergoing Carticel® (autologous cultured chondrocytes) implantation will need to follow a strict rehabilitation program. Although specific exercises and length of the rehabilitation period may differ from patient to patient, your surgeon and physical therapist will recommend a program for you based on the size, location, and severity of your cartilage injury.

When will I be able to walk after surgery?

Walking without the assistance of a crutch or cane can generally begin between 3-5 months. Consult your surgeon or physical therapist for specific recommendations.

When can I start playing sports again?

That depends upon the length of your rehab and the specific sport you are playing. Generally, low-level activity such as swimming, biking, walking, or skating, may be resumed as early as 6 months following treatment. More strenuous activity involving pivoting or twisting, like basketball, soccer, or tennis, should generally not occur until 12 months post-treatment. Individual results may vary. Not all patients return to full activity.

What if I've been treated with another procedure?

If you've been treated with another procedure, and are still experiencing pain and swelling, you may be a candidate for Carticel. Questions regarding additional medical treatment for articular cartilage damage should be directed to your orthopedic surgeon.

Can any surgeon treat me with Carticel?

No. Only surgeons specially trained in the implantation technique may perform the procedure. To locate a surgeon who can perform the procedure in your area, call Physician and Patient Services at 1-800-453-6948.Will my insurance company pay for this surgery? Generally, most insurance plans will cover the procedure. You should contact your plan administrator for details.

When can I drive a car?

This depends on the size, location, and severity of your defect. However, your surgeon may allow you to begin to drive as early as four months following your surgery.

How long will I have to stay in the hospital following surgery?

This depends on the complexity and severity of your cartilage injury and if a concurrent procedure is performed at the time of implantation. Less complex injuries, you can expect to be hospitalized for one day; more complex injuries, a multi-day hospital stay is not uncommon.

Can I take aspirin or ibuprofen before and after surgery?

Aspirin should be discontinued 7-10 days prior to surgery. You may consider switching to Acetaminophen. Following surgery, ice therapy works well. You should consult your surgeon before taking specific medications before and after surgery.

If I smoke cigarettes, do I need to stop before having surgery?

As with most surgeries, you should refrain from smoking the day you have your procedure performed.

Can I shower with the stitches or staples?

This is dependent upon the recommendation of the surgeon; however, usually a shower can be taken following surgery, but the knee needs to be covered with plastic.

When will I start continuous passive motion (CPM) exercises?

Six to twenty-four hours following surgery; 6-8 hours/day for 2 weeks.

How long will I be on crutches?

For the first 7-8 weeks, crutches are used with minimal weight applied to the injured leg. After 2-3 months, you may switch to a cane. Please consult your surgeon or physical therapist for specific recommendations regarding the use of crutches or a cane.

When does physical therapy start?

Physical therapy usually starts one week following surgery. Therapy runs approximately 2-3 days per week for 6-8 weeks. During weeks 8-16 gradually increase to full weight bearing/walking. By week sixteen, home exercises are started. Specific therapy programs may vary from patient to patient. Please consult with your surgeon for your specific program.

Can I go in a hot tup or Jacuzzi?

Yes, at weeks 3-4 when the incision has healed, however consult with your surgeon for specifics.

Will there be a scar?

Yes, there will be a scar, but with time it will fade. One scar is over the knee and the other is over the shin.

Is it painful?

Yes, since it is a surgical procedure you may experience pain, however, the pain is controllable.

What else do I need to know about the Carticel (autologous cultured chondrocytes) procedure?

Carticel is indicated for the repair of symptomatic, cartilaginous defects of the femoral condyle (medial, lateral, trochlear), caused by acute or repetitive trauma, in patients who have had an inadequate response to a prior arthroscopic or other surgical repair procedure. The product is not recommended for use in patients with a known history of allergy to the antibiotic gentamicin, in patients with sensitivities to materials of bovine origin, who have an unstable knee, or who have abnormal weight distribution within the joint. Patients who have previously had cancer in the bones, cartilage, fat, or muscle of the treated limb should also not be treated with Carticel. Any instability of the knee or malalignment of the joint should be corrected before or concurrent with Carticel implantation. Use in children, or in joints other than the knee has not yet been assessed. Data regarding outcomes beyond 3 years are limited. In patient data included in the biologics license application, the following were the most frequently reported adverse events: "overgrown" tissue at the site of the cartilage repair, adhesions, superficial wound infection, inflammation of membranes within the joint, and post-operative bruising.