Efficacy Evaluation of a New Hyaluronan Derivative HYADD(®) 4-G to Maintain Cartilage Integrity in a Rabbit Model of Osteoarthritis

OBJECTIVE: To test the efficacy of a hyaluronan derivative (HYADD(®)4-G) in a model of osteoarthritis (anterior cruciate ligament [ACLT]) and to compare its efficacy with the injection of growth factors. DESIGN: In a first experimental set-up, specially selected for treatment scheme with published studies on hyaluronan or growth factor efficacy in osteoarthritis, saline, HYADD(®)4-G, rh-BMP-7, and the treatments of rh-BMP-7 or rh-BMP-2 with HYADD(®)4-G were injected after ACLT, for five times starting 3 weeks after ACLT. Euthanasia was at day 70. The knees were evaluated by gross morphological observation, x-ray, and histology (Study A). In a second experimental set-up selected to evaluate the efficacy of three viscosupplement injections, starting 4 weeks after ACTL, HYADD(®)4-G was compared to saline (Study B). RESULTS: (A) X-ray analysis showed more damage in the saline group than all other treatment groups (2.67 ± 0.61 for saline, 0.83 ± 0.26 for HYADD(®)4-G, 1.67 ± 0.82 for HYADD(®)4-G with rh-BMP-2, 0.75 ± 0.76 for HYADD(®)4-G with rh-BMP-7, and 1.58 ± 0.49 for rh-BMP-7), P < 0.05. In the femoral condyle, the Mankin’s score for HYADD(®)4-G with rh-BMP-2, HYADD(®)4-G with rh-BMP-7, and rh-BMP7 alone was statistically lower compared to saline in the medial part; in the lateral part a significant lower value was observed in the HYADD(®)4-G with the rh-BMP-2 group. (B) The Kellgren and Lawrence score and Mankin’s score was lower in the HYADD(®)4-G group than in the saline group (P < 0.002 and P = 0.0031). CONCLUSIONS: These two studies suggest that HYADD(®)4-G delayed the cartilage degeneration and that the association of HYADD(®)4-G with growth factors is synergistic.