Thursday, March 19, 1998
The 1998 Kappa Delta Awards will be presented for orthopaedic research during Opening Ceremonies of the 65th Annual Meeting of the American Academy of Orthopaedic Surgeons which begins at 3:45 p.m. today in the La Louisianne Ballroom of the Morial Convention Center.
The researchers will present the results of their award-winning studies during the joint program of the Academy at the Orthopaedic Research Society at 10:30 a.m. today in the La Louisianne Ballroom. Their research focuses on new techniques to reduce wear in hip replacements, basic research on the biomechanical environment of the chondrocyte in articular cartilage and in monoclonal antibody technology.
Harry A. McKellop, PhD, and four colleagues will receive the Ann Doner Vaughn Award for developing a modified polyethylene with improved wear resistance that could help to prevent loosening failure of total hip replacements. Wear of the ultra-high molecular weight (UHMW) polyethylene cup used in hip replacement components produces billions of submicron wear particles each year that, over time, can cause osteolysis and component loosening. "Substantially improving the wear resistance of the polyethylene could be the single most effective way to extend the clinical lifespan of total hip prostheses," reported McKellop, associate professor of orthopaedics and biomedical engineering at the University of Southern California, and director of the J. Vernon Luck Orthopaedic Research Center at Orthopaedic Hospital in Los Angeles.
The team's research showed that the long-term wear properties of the UHMW cups are markedly affected by the method of sterilization used by the manufacturer. One method, gamma irradiation, causes oxidative degradation which can reduce the cup's resistance to wear, but irradiation also induces a chemical reaction called crosslinking, which improves the resistance of UHMW polyethylene to the type of wear that occurs in a hip prosthesis. While nonradiation sterilization techniques such as ethylene oxide or gas plasma do not cause oxidation, they also do not induce cross-linking.
In a series of studies comparing the two basic methods, the researchers had cups prepared from a single original batch of polyethylene by five different manufacturers, and compared their wear resistance in a hip joint simulator, both prior to and after the cups were artificially aged by heating them to 80 degrees centigrade to accelerate the oxidative degradation. "Without artificial aging, the two types of cups that were gamma-irradiated while in low oxygen packaging exhibited about 50 percent lower wear rates than cups that were not sterilized or were sterilized without irradiation, and this advantage persisted after 14 days of artificial aging," McKellop reported. "Only after extensive oxidation, caused by heating for 30 days, did the wear rate of the cups that were irradiated in low-oxygen exceed that of the nonirradiated cups."
In retrieval studies by this and other groups, this severe level of oxidation has occurred only rarely, and probably included the effects of long-term shelf storage. Consequently, most manufacturers now recommend against extended shelf storage prior to implantation, and radiation-sterilized cups should be stored while sealed in the low-oxygen packages.
Although McKellop emphasized that the choice of a particular method of sterilization should be based on a careful review of all of the recent literature, he reported that "the results of our laboratory simulations indicated that the long-term wear resistance of UHMW polyethylene cups that have been sterilized by irradiation in a suitable low oxygen package should be substantially lower than that of non-irradiated cups at least during the first decade of use, and probably longer."
In a third phase of the research, McKellop's team developed two methods for producing polyethylene cups with crosslinking greater than that which occurs simply as a byproduct of routine gamma sterilization. They found that with sufficient crosslinking the wear in the hip simulator was reduced to an immeasurably small level. "However, since crosslinking of polyethylene also can reduce its yield strength, fatigue strength and elongation to failure, an optimum balance must be obtained between these important physical properties and the wear resistance," he said. McKellop also emphasized that these results might apply only to the type of wear occurring in hip prostheses, and very different tradeoffs might hold for knee prostheses, in which the cyclic stresses on the polyethylene can be much greater.
Other members of the research team from the Orthopaedic Hospital included Fu-Wen Shen, PhD, a research fellow; Bin Lu, MS, manager of the Tribology Laboratory; Patricia Campbell, PhD, director of the Implant Retrieval Laboratory; and Ronald Salovey, PhD, professor of Chemical Engineering, University of Southern California.
Farshid Guilak, PhD, assistant professor in the Duke University Orthopaedic Research Laboratories, will receive the Young Investigator Award for basic research on factors that lead to the breakdown of cartilage in osteoarthritis, a painful and debilitating disease which affects millions of people.
The cartilage cells utilize chemical and mechanical signals from the surrounding environment in conjunction with their genetic programming to control their activity. For instance, cartilage in an immobilized joint will waste away, while cartilage that is overstressed with mechanical loading will break down. "The overall goal of our studies has been to quantify the mechanical signals that the chondrocytes are exposed to under normal circumstances" and to determine what levels of mechanical loading are required to maintain a healthy joint, Guilak said. Currently, the team is trying to define the characteristics of the signals and the chemical pathways "that the cells use to translate mechanical signals into biological ones," Guilak said.
To do this, the team grew living cartilage in a tissue culture system so they could "investigate the influence of mechanical stress on cell metabolism," he said. The team discovered that mechanical stress can induce some of the characteristics of osteoarthritis in cartilage. "Using a mathematical technique known as finite element modeling, we have been able to predict the stresses that are placed on single cells within cartilage," reported Guilak. With the three-dimensional confocal microscopy system, he said the team "can identify the biological events which occur inside a single cell within milliseconds after a mechanical stress is applied to the cell."
A major focus has been to determine the differences between normal and osteoarthritic cartilage, said Guilak, noting that the disease diminishes the ability of cartilage tissue to carry loads. "Cells in osteoarthritic cartilage are exposed to significantly different mechanical signals than normal cells." He attributed the differences to a change in the structure and stiffness of the pericellular matrix, a thin region of tissue which surrounds each cell in cartilage and to its ability to regulate cell volume in response to the mechanical stress.
"Our findings may have important implications to the field of tissue engineering, where researchers are attempting to produce living tissue substitutes to replace damaged or diseased cartilage," suggested Guilak.
Research on monoclonal antibody technology "has made several significant novel contributions that have now changed our knowledge of proteoglycan structure, function, and metabolism in musculoskeletal tissues," reported Bruce Caterson, PhD, professor of biochemistry from the University of Wales, Cardiff. Caterson will receive the Elizabeth Winston-Lanier Award for his historical review of l7 years of pioneering research on monoclonal antibody technology at the University of Wales Connective Tissue Biology Laboratories at the School of Molecular and Medical Biosciences.
"Our original intent was aimed at producing monoclonal antibodies directed against protein epitopes in proteoglycans," reported Caterson. "However, we were the first laboratory to produce antibodies against epitopes in keratan sulfate glycosaminoglycans, structures that were previously thought to be nonimmunogenic because of their highly conserved presence in nature and throughout evolution." His lab recorded a number of other firsts, including the "development of antibody technology that specifically recognizes the occurrence of catabolic neoepitopes on proteoglycan degradation products produced during normal turnover and in pathological destruction of cartilage by aggrecanase. "These technologies are being used to study mechanisms of cartilage degradation in arthritis, the development of specific means of monitoring proteoglycan catabolites in body fluids, and also for novel drug discovery programs aimed at slowing the progression of cartilage destruction in arthritis," Caterson reported.
This lab has focused on the development and use of immunological procedures to study subtle changes that occur in the biochemistry of cartilage proteoglycans during the pathogenesis of osteoarthritis. Changes in chondrocyte metabolism in osteoarthritis produce compositional changes in the newly synthesized proteoglycans. Caterson reported that "these biochemical changes occur in an attempt to remodel or repair the tissue as a response to its altered mechanical environment where subtle changes in cartilage biochemistry are reflected by the synthesis of new structures within the complex macromolecules that comprise the cartilage extracellular matrix."
The lab's special antibodies have been used by researchers
throughout the world to identify subtle changes in cartilage cell
metabolism that can lead to degenerative joint disease, reported
|1998 Academy News Mar.19 Index C|