New York—July 13, 2013
“The results at this time are encouraging,” said lead author of the study Scott Rodeo, M.D., orthopedic surgeon and co-chief of the Sports Medicine Service at Hospital for Special Surgery, in New York City. “De Novo NT compares favorably to our existing techniques, given that it is easy to do and involves a one step procedure. We are cautiously optimistic. It clearly regenerates tissue, but we need further long-term followup.”
The smooth, white tissue covering the ends of bones where they come together to form joints is called articular cartilage. In the knee, this cartilage can be damaged by a traumatic sports accident, a bad fall, or normal wear and tear in active individuals. Articular cartilage lesions can cause pain and lead to osteoarthritis. “Articular cartilage injuries to the knee are fairly common, and they are hard to treat,” said Dr. Rodeo. “Cartilage has no capacity to heal spontaneously, and cartilage lesions over time can get progressively larger.”
There are no perfect options for treating articular cartilage lesions, but current therapeutic approaches include surgeries such as microfracture, a procedure that involves drilling small holes in bones to induce bleeding and spark healing. Surgeons can also use donor tissue that can be sized and fitted to the defect, but donor tissue is in limited supply and reestablishing congruity of the cartilage surface using this method can be difficult.
De Novo NT is an FDA approved cartilage repair technique. The product is made out of minced cartilage from organ donors under the age of 13. Unlike cartilage in adults, this young tissue has a high proliferative capacity. Cells from the transplanted cartilage escape or migrate into surrounding area tissues, multiply, and form a new cartilage tissue matrix that integrates with the surrounding host tissue. This technique eliminates the need for harvesting and requires less suturing because the product uses a fibrin sealant to secure the particulated tissue pieces into the lesion. Fibrin is an insoluble “sticky” protein involved in the clotting of blood.
“The small pieces of juvenile cartilage are less than a millimeter in size, and what happens is the cells can migrate out of these small pieces of cartilage,” said Dr. Rodeo. “We are trying to take advantage of the high proliferative capacity of the tissue.”
Until now, only a few case-reports of this product have been published. The tissue graft falls into a category of products that does not have to undergo the rigorous clinical trial process through which drugs, for example, are approved.
In the study presented at the AOSSM meeting, clinicians used De Novo NT to treat 17 patients who had cartilage damage on the kneecap (specifically focal patellofemoral cartilage lesions). The average lesion size was 203 millimeters. Clinicians compared symptom assessment survey data and MRI images at baseline and at two years of followup and identified improvements in all patients.
At two years of followup, patients had roughly a 30% improvement in scores from the international knee documentation committee (IKDC) health evaluation form, a 20% improvement in the IKDC subjective form, and a 25% Knee Outcome Survey form (53.5 vs. 75.5). These surveys gauge the degree of symptoms, such as knee swelling and pain, that a patient is experiencing and how much knee impairment impacts overall well-being, activities of daily living, work, and athletic and social activities. “The improvements are clinically significant, as well as statistically significant,” said Dr. Rodeo.
The patients also showed improvements on MRI scans, with traditional MRI technology as well as quantitative T2 mapping MRI. T2 mapping, which evaluates biochemical changes in the cartilage, was developed by HSS investigators including Hollis Potter, M.D., chief of the division of magnetic resonance imaging, director of research in the Department of Radiology and Imaging at HSS. T2 mapping in 6 patients showed prolongation of quantitative T2 values in both the superficial (58.6 vs. 37.4; P=0.02) and deep components of the repair tissue (47.18 vs. 28.3; P=0.005), demonstrating that the tissue still differs from normal cartilage.
“Quantitative MRI, when combined with morphologic assessment, allows us to understand the natural history of repair techniques,” said Dr. Potter, who was also involved with the study presented at AOSSM. “We gain knowledge about the biology of integration with the host tissue, as well as the repair tissue biochemistry (collagen orientation), all by a noninvasive imaging technique.”
Adverse events seen in patients, such as swelling and inflammation, were typical postoperative complications seen after other cartilage repair strategies.
“Using symptom outcome scales, we have demonstrated symptomatic improvement, and we have used MRI to carefully evaluate the regenerative tissue,” said Dr. Rodeo, who pointed out longer followup is needed. “We need to perform MRIs on a yearly basis to follow the maturation of the tissue.”
De Novo NT Natural Tissue Graft is manufactured by Zimmer Incorporated.
Other researchers from Hospital for Special Surgery involved in the study are Cecilia Pascual-Garrido, M.D., Stephanie L. Gold, M.S., Jaclyn Snikeris B.S., Alissa Burge, M.D., Joseph Nguyen, MPH, Russell F. Warren, M.D., and Riley J. Williams, M.D.
About HSS | Hospital for Special Surgery
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the ninth consecutive year) and No. 3 in rheumatology by U.S.News & World Report (2018-2019). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In 2017 HSS provided care to 135,000 patients and performed more than 32,000 surgical procedures. People from all 50 U.S. states and 80 countries travelled to receive care at HSS. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The culture of innovation is accelerating at HSS as 130 new idea submissions were made to the Global Innovation Institute in 2017 (almost 3x the submissions in 2015). The HSS Education Institute is the world’s leading provider of education on the topic on musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.