Contributing Writer

Canadian researchers believe they have found an alternative to bone marrow stimulation and total knee replacement for patients suffering from severe knee cartilage loss or osteoarthritis.

Developed by Biosyntech Inc., of Laval, Quebec, BST-CarGel is a liquid polysaccharide that is mixed with the patient's own blood to form a gel that stimulates regeneration of cartilage. Matthew Shive, Biosyntech's vice president of product development, said the product has been made available to three patients under Health Canada's Special Access Program.

The program provides a mechanism "for using devices that are not approved in Canada but given to patients on compassionate grounds," Shive said. "It's for those patients who don't have alternatives other than total knee replacement, [and] where the quality of life following total knee replacement is poor."

Under Health Canada regulations, BST-CarGel is classified as a medical device because it serves a "scaffolding" function for the blood-gel mixture.

"If it was an injectable plastic that actually solidified in the cartilage, I think people would understand it to be a device," Shive said. "Here we have something like that, but it just happens to be replaced by new cartilage."

During the placement procedure, CarGel is administered using an arthroscopic technique called microfracture, in which holes are drilled into the bone underlying the cartilage lesion. That allows stem cell-rich bone marrow to seep out and mix with the CarGel to provide what Shive calls a "voluminous repair environment."

"So, we actually have two things that are occurring here," he said. "One is we have supplied a blood clot, and we have allowed bone marrow stem cells to come from below. Those cells will then come into this voluminous repair environment, where you have additional blood factors, platelet growth factors, etc., which facilitate growth of the new tissue."

The CarGel scaffold eventually disintegrates, once new cartilage has been generated.

Shive said BST-CarGel is similar to bone marrow stimulation in that it encourages the migration of blood cells to the affected area of the knee. The difference is that CarGel also is mixed with autologous blood and is administered directly to the bone surface of the knee to form a blood clot. CarGel prevents the blood clots from contracting, which in turn generates new cartilage.

"We've taken that good idea of getting into the bone marrow with something that's easy for surgeons to use," Shive said. "It's still arthroscopic, it doesn't tack on another surgery, the recovery time for the patients is still fast, and the results thus far have been great."

CarGel has been injected into rabbits, horses and sheep at 700 times to 800 times the human dose, with no toxicity reported, Shive said. But the real excitement occurred on Aug. 19, when the product was administered to its first human.

Former Montreal Canadiens hockey star Serge Savard had been so impressed by CarGel in its early stages of development that he invested in Biosyntech. In fact, he became chairman of the board in 2002.

During examination of Savard's knee, orthopedic surgeon Nicolas Duval discovered that a large area of the weight-bearing portion of the knee was gone, and he told the 57-year-old former athlete that his options were limited.

"If I were to show Mr. Savard's X-ray to one of my colleagues," Duval said, "he would immediately tell me it's impossible to do anything else but a total knee replacement.

"But Mr. Savard is a big guy, at 6' 4" and 250 pounds, and we know that for a young patient like him total knee replacement would be very likely to fail after 10 years. So the challenge was to grow enough cartilage - maybe not enough to make him pain-free but give him a painless knee for daily activities, such as walking, golfing and cycling."

Two more patients have undergone the procedure since then, and while it is still too early to judge the ultimate effectiveness in those cases, Duval said he's encouraged.

"From what I see of the first three patients that I have done, I am very impressed with the result," he said.

Shive stressed that CarGel helps to produce genuine cartilage, not fibrocartilage, which is chemically different from real cartilage, lacks the mechanical properties of real cartilage and degrades over time. Both bone marrow stimulation and the product Carticel, from Genzyme Biosurgery, a division of Genzyme Corp., of Cambridge, Mass., produce fibrocartilage, he said, and while initial reports from patients who have undergone those therapies might be positive, the results may not be long-lasting.

"In the beginning they had pain; after the surgery, maybe they didn't have pain, but the question remains, did they repair the cartilage?" he said. "Well, not really. They put something that's inferior cartilage in there."

Shive said a lack of controlled trials also has made it difficult to judge the success of past treatments and products for damaged cartilage and osteoarthritis. In their work, however, researchers at Biosyntech use pain surveys given to patients to determine their progress at various stages after CarGel injection.

While CarGel was developed principally for cartilage defects in young athletes, Duval believes patients as old as 70 and suffering from osteoarthritis might eventually become good candidates for the procedure. Nor will the use of CarGel be limited to damaged knees, he added.

"Currently, this is only for the knee joint, but if it proves successful for the knee joint then the same thing could be done for ankle joints, [and] could be done for hip joints," he said.

Biosyntech expects European approval of CarGel to be granted early next year. North American clinical trials also will begin shortly, with approval from Health Canada and the FDA expected to follow over the next year.