Biomedicine

Regenerating Torn Cartilage

A new biomaterial could improve knee-cartilage repair surgery.

A new biomaterial developed by Cartilix, a biotech startup based in Foster City, CA, could dramatically improve the success rate of knee-cartilage repair surgery, making the procedure more accessible to patients with bad knees. The new material, called ChonDux, consists of a polymer hydrogel that, when injected into the knee during surgery, guides the regeneration of cartilage by stimulating repair cells in the body.

Knee filler: A biomaterial developed by Cartilix, called ChonDux, could improve current microfracture surgery aimed at repairing damaged knee cartilage. During the procedure, the surgeon applies a bioadhesive (shown in blue) to the cavity where the cartilage is missing. Tiny holes (red) are then drilled in the bone next to the cavity and filled in with hydrogel (wavy lines). UVA light is shined on the material, which causes the polymer to harden from a viscous liquid into a gel (crosshatched lines).

The minimally invasive knee surgery known as microfracture, in which a surgeon drills holes in the knee to stimulate the regeneration of cartilage lost from wear and tear, has become increasingly popular among athletes in recent years. A number of professional basketball players, including Greg Oden of the Portland Trail Blazers and Amare Stoudemire of the Phoenix Suns, have undergone the procedure, contributing to its rise in popularity. However, the procedure’s success rate varies dramatically, says Norman Marcus, an orthopedic surgeon at the Virginia Cartilage Institute, in Springfield, VA. Among young athletes who have small defects in their knee cartilage, microfracture works up to 75 percent of the time. However, that number drops to 50 percent in older patients, Marcus says.

Marcus, who is chief medical officer at Cartilix, and his colleagues hope to improve the procedure and make it more accessible to the larger population of baby boomers. As people age, many are forced to curtail their physical activities due to painful, swollen joints caused by the deterioration of cartilage in the knee that comes with age or results from repetitive stress or injury. Marcus hopes to be able to treat these patients before they develop full-blown osteoarthritis. “The goal is to identify that big population that wants to be active throughout their entire lives,” he says.

During microfracture, a surgeon uses a special awl to drill a series of tiny holes into the bone underneath the area of missing cartilage. Bone marrow containing stem cells seeps into the damaged area and forms a clot. The clot releases stem cells, which differentiate into cartilage cells and gradually form new tissue. However, because the new tissue is scar cartilage, not true cartilage, it may not have the same durability and strength as the original tissue–a likely contributor to the high failure rate of microfracture.

ChonDux consists of a hydrogel made of polyethylene glycol–a polymer commonly used in a variety of medical products–and a bioadhesive to keep the hydrogel in place after injection. First, the surgeon coats the inside of the cavity where the cartilage is missing with the bioadhesive and then, as in microfracture, drills tiny holes into the bone next to the cavity. Then the surgeon fills the empty space with the hydrogel and shines UVA light on the material, which causes the polymer to harden from a viscous liquid into a gel.The blood clot that forms from the microfracture then gets trapped in the hydrogel.

One of the biggest problems with transplanting biomaterials is getting the mostly aqueous material to stick in a very slippery space, says Jennifer Elisseeff, a biomedical engineer at Johns Hopkins University, who developed ChonDux and cofounded Cartilix. The adhesive in this case consists of chondroitin sulfate–a natural component of cartilage that is chemically modified to bind to the healthy cartilage surrounding the defect, as well as to the hydrogel. “It acts like a primer that helps paint stick to the wall,” Elisseeff said at a panel at the recent EmTech conference in Cambridge, MA. The adhesive prevents scar formation between the new and old cartilage.

Elisseeff, who was a member of Technology Review’s TR35 in 2002, and her team have tested the material in rabbits and goats and have found that more cells from the bone marrow get trapped in the blood clot when the hydrogel is present, compared with microfracture conducted without the gel. The researchers also noted that the defects fill faster with the biomaterial than without, and that the newly formed tissue more closely resembles true cartilage.

Results from a small clinical trial in Europe also look promising. According to findings presented at EmTech, magnetic resonance scans of the knee six months after the procedure showed that patients who received the hydrogel had grown more tissue than those undergoing traditional microfracture, and they reported less pain. Cartilix hopes to submit the data from its European study to the U.S. Food and Drug Administration (FDA) and begin a larger human trial in the United States.

While there are a number of studies on different carriers, such as hydrogels and other biomaterials, that can hold the cells in place and grow cartilage, “what’s exciting about this work is that this bioadhesive can hold the hydrogel in place fairly strongly, giving it time to regrow cartilage,” says Farshid Guilak, a biomedical engineer at Duke University School of Medicine. And because the biomaterial doesn’t need to be seeded with cells prior to injection–a strategy that many research groups are investigating–it might be easier for Cartilix to obtain FDA approval for the material.

Elisseeff is adapting her biomaterials for other applications as well. For instance, she recently licensed some of her technology to Kythera Biopharmaceuticals, a company based in Calabasas, CA, that specializes in cosmetic medicine. The company is using Elisseeff’s materials to develop light-activated cosmetic fillers that last much longer than those currently on the market. These fillers, which are typically injected into the skin along the sides of the mouth to minimize wrinkles caused by aging, tend to have a short life span. Patients often have the procedure repeated several times a year.

“With our materials, we shine light over [the area of the skin] that was injected and cross-link the materials so that they don’t degrade as quickly,” says Elisseeff. She says that Kythera plans to test the cosmetic fillers in patients in a couple of months. The first pilot study will take place in Beverly Hills.

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