Building a cartilage bridge

Regentis's tissue regeneration technology helps sports injuries heal themselves.

The cash shortage that Israeli biomed companies face usually forces them to opt for a strategy of "starting off small," meaning to start by developing an application that can be commercialized within a short time and at the lowest possible investment, even if it is not the most profitable.

But although Regentis Materials Ltd. began as an incubator company without much in the way of capital, it decided, so says its founder and CEO Yehiel Tal, to do exactly the opposite, and choose the toughest challenge of all. "No one had ever managed to generate knee cartilage with properties similar to original cartilage. When we entered the Technion incubator, we presented our technology to a visiting delegation from Johnson & Johnson, who told us it could be suitable for this application, and that despite the risk being higher than any of the other applications the technology was suited to, it would deliver the highest return as well. So we decided to go for it," he recalls. The challenge that Tal and the Regentis team were set by the incubator in September 2004 was clear. "They told us, 'you have to develop knee cartilage in lambs within 14 months.' I'm not sure whether I would take on a task like this today." But to Tal's delight, although the work was grueling, the task was accomplished.

Growing replacement tissue for human tissue is a field that has evolved in its present form over the last ten years. Replacement tissue is usually produced from live cells taken from a biopsy of tissue from the patient himself. Prochon Biotech Ltd., where Tal worked previously, specializes in this field, and has developed a unique artificial matrix that encourages cells to grow in a predetermined shape.

The idea that Regentis has conceived to differentiate itself from its competitors is a surprising one - its replacement cartilage does not include live cells. In fact, it has expunged the tissue itself from the underlying concept behind its alternative tissue. Instead, it has formed a form of interim synthetic bridge which when applied to the injured limb, allows natural tissue to grow and regenerate. The company regulates the rate of the synthetic product's disintegration, in tandem with the growth of natural tissue.

"When body tissue has been damaged, a blood clot is usually formed which also acts a bridge for the building of new tissue and sends a signal that promotes tissue building. The problem occurs when the damage is too extensive and the blood clot can't create the bridge. Once that happens it disintegrates fairly quickly," says Tal.

Regentis's product combines a protein called fibrinogen, a substance produced by the body and connected to the clotting process, and a synthetic polymer. "We bind the polymer's fibers to those of the fibrinogen. The body has enzymes that break down this bond, and our control over the level of breakdown is essentially the control over the complex polymer structure around the fibrinogen. The more complex the structure is, the more difficult it is for the enzyme to penetrate it, and the implant can last for up to a year without breaking down. It is very much like the process of coating drugs with synthetic materials to enable a slow release," says Tal. Biological implants with cells are known to encourage natural healing in the cartilage, but according to Regentis, they do not last long enough to complete the process, which in a knee can take between six months and a year.

Globes: A number of companies with biological products told me that they can control the rate of disintegration for up to a year.

Tal: We've never heard of anything like this.

A patent instead of an article

Tal began his career at the Faculty of Mechanical Engineering at the Technion Israel Institute of Technology where he graduated with a bachelor's and master's degree. He served as director of business development and business unit manager at Kulicke and Soffa Industries Inc. following which he joined OrthoScan Technologies Ltd. as VP marketing and business development, where he was first exposed to medical device technologies. He then served as VP business development at Prochon, where he met Dror Seliktar, now a professor at the Technion's Biomedical Engineering Department, who joined Prochon to carry out related research. Seliktar asked Tal if the product could be commercialized, and after studying the issue Tal stopped Seliktar from publishing an article about it, and instead the two men patented the idea. Prochon preferred not to commercialize the product and Tal decided to leave and set up Regentis together with Seliktar.

Since he was a graduate of the Technion, Tal consulted the Technion Entrepreneurial Incubator Co. Ltd. (TEIC), but says that because he was prejudiced, incubating with TEIC was not his first choice. "I learned later on, that a company like ours is not mature enough to raise funding and would be better off maturing in an incubator with all the support, including laboratories, experts, and even public relations. TEIC recently completed its privatization and that was a great help to us when we came to decide. It is managed by four leading funds - Vitalife Vertex, Venture ProSeed, and the US fund Battery Ventures, so obtaining follow-on funding will be fairly easy. We've already received $600,000 in investment - more than the minimum set under the incubation program."

Regentis is now focusing on the replacement of cartilage that has been damaged through sports injuries and accidents, for example, rather than cartilage that has been gradually worn away. The current method of treating knee cartilage damage is through an arthroscopy - the insertion of a tube through which tissue parts and loose shreds are removed, but the cartilage continues to get worn down, and will eventually need cleaning again. At some point, the entire joint has to be replaced by a knee made from substitute materials in a highly complex surgical procedure. 700,000 arthroscopies and 300,000 knee replacements are carried in the US every year.

"There's a process called 'micro fracture' where tiny fractures are made to allow the blood to flow to the cartilage and speed up healing," says Tal. "This creates a blood clot that helps healing but, as I mentioned, it breaks down too quickly. This process does help grow new tissue but it is not of the same quality as the original tissue. In our treatment, the tissue grows on the base of the bridge we built throughout the process and it is of a superior quality. So you need less of the hospital treatment and physiotherapy the insurance companies are so fond of."

Another advantage of the product is its unique form of delivery. Were it necessary to build a three dimensional tissue and implant it as such inside the body, major surgery would be necessary. Regentis has found a method of introducing the substance into the body in fluid form, by simple injection. Ultraviolet light is then projected up the opening the fluid has been injected through. The fluid crystallizes into a gel-like substance and fills up the area where tissue is missing. The polymer gradually breaks down in the body and is excreted in the urine. "These are commonly-known substances that are now used in products that pass through the body," says Tal.

After three years in the incubator Regentis conducted a feasibility trial on animals, following which it raised $7.5 million, which will enable it to carry on for the next two and half to three years. The next stage will be trials on humans, under the medical device category, and these are due to begin in a year's time.

Why can't the product be used to treat age-related natural cartilage degeneration, which is a massive market?

"We may focus on this indication later as well, but the trials are longer and more complicated. The product may also have to undergo some changes to be suited for use in this indication. The field we're targeting is a niche - but a major niche in its own right."

Published by Globes [online], Israel business news - www.globes.co.il - on January 2, 2008

© Copyright of Globes Publisher Itonut (1983) Ltd. 2008

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