Frenkel Lab: Projects

Project: Extending Implant Longevity

Joint replacement surgery, in which an artificial hip or knee (for example) is implanted in place of a severely diseased or damaged joint, relieves pain and restores mobility, granting a pain-free existence to millions. Unfortunately, even the best joint replacement devices eventually loosen; when this happens, a second operation is required to replace the compromised device. This becomes an even greater problem as life spans continue to increase. Furthermore, a variety of new drugs for related conditions (e.g., osteoporosis) are being administered to joint replacement patients—drugs that may interfere with prosthesis performance.

Evidence of implant loosening. This x-ray reveals that the acetabular component ("socket") of this hip replacement prosthesis has loosened over a period of years. (The arrow indicates the area of significant bone loss.) Currently such a condition requires a second, more complex operation to restore bone stock and replace the implant.

A variety of approaches to this problem have been taken in the past, including the use of new types of implant cement and treating implant surfaces with special coatings and textures. Dr. Frenkel’s research in this area has concentrated on stimulating early integration of implant and surrounding bone so as to achieve optimal device longevity. We are currently focusing on developing materials that mimic natural bone and encourage long-term bone-implant interlock. The use of hydroxyapatites (bone mineral) and experimental implant surface texturing are among the approaches being investigated. We are also performing animal studies in which drugs often used by joint replacement patients are being administered, and the subsequent success and longevity of the prosthesis is being examined.

Several candidate implant coatings and texturings are under investigation. Data from studies performed short-term (up to six months) are encouraging, and long-term studies are now under way that will serve to confirm our first findings and suggest new directions in treating this problem. We have demonstrated that these improvements result in rapid bone attachment to the implant and increased mechanical strength over time.

Schematic of implantable chamber. Simulated implant surfaces employing different materials and or surface treatments can be tested in vivo in a polyethylene implant chamber developed in our laboratories.

Project: Using Growth Factors to Enhance Cartilage Repair

Joint pain is a major cause of disability not just in middle-aged and older people, but also among those who suffer sports injuries and other forms of trauma. The pain is usually caused by the injury itself and subsequent degeneration of the cartilage at the joint surface.

The effectiveness of widely advertised over-the-counter pharmaceuticals (most notably glucosamine and chondroitin sulfate) are unproven in scientific studies. One common surgical treatment involves scraping away damaged areas of cartilage; this is a stopgap measure to relieve pain, not a cure, and it may lead to further deterioration. Another approach involves transplanted chondrocytes (cartilage cells); this is still an experimental procedure that requires two operations. As a last resort, joint replacement is recommended.

A long-time goal of Dr. Frenkel’s research has been to find new ways of repairing lesions in cartilage so as to prevent the future onset of arthritis and obviate joint replacement. For the last 15 years, she has focused on designing a device to stimulate cartilage to heal itself, something it is not normally capable of doing.

How growth factors can help repair cartilage. Microphotographs of the cartilage surface of rabbit knee implanted with carrier device containing cartilage cells, or growth factor, or untreated device: (top) Device alone results in uneven surface, and little normal cartilage matrix (the tissues are stained red); (center) device with cells induces formation of a smooth, regular surface, but little matrix stain is seen; (bottom) device containing growth factor results in smooth surface with healthy matrix staining.

A variety of implant systems have been developed by orthopaedic researchers. The majority involve materials designed to deliver replacement cells to the damaged area in order stimulate new cartilage growth as replacement for cells lost to injury or normal wear and tear over time. While these materials are compatible with cell survival and are eventually incorporated into the joint surface, this approach requires that healthy cells be surgically collected from the patient, then grown to large numbers in the laboratory, followed by a second surgery for implantation.

Ideally, if a device could be designed to stimulate the cells already present in the joint to repair the injury, surgery to collect the cells could be bypassed, reducing both patient pain and costs. An initiative recently instituted in our laboratories employs natural substances called growth factors in implants in lieu of cells. We anticipate that these factors will attract cells to the site of injury and stimulate them to produce a repair cartilage that will regenerate the damaged joint surface and permanently relieve pain. A regenerated surface would also prevent further deterioration of the joint to arthritic conditions. Early results of our short-term studies indicate that growth-factor-treated-implants induce a repair as good as those using cell-seeded devices. Long-term studies in large animals, now in the planning stage, will gauge the success of this approach in producing a permanent solution to this currently debilitating problem.