Therapeutic Effects of Intra-Articular Ultrapurified Low Endotoxin Alginate Administration on Experimental Osteoarthritis in Rabbits

Abstract

Objective:We have developed an ultrapurified low endotoxin alginate (UPLE alginate), which can drastically reduce endotoxin levels. Our purposes were to examine the effects of UPLE alginate administration on osteoarthritis (OA) progression and to determine the adequate molecular weight of the UPLE alginate for therapeutic effects.Design:To induce knee OA, 35 Japanese White rabbits underwent anterior cruciate ligament transection. Intra-articular injections of 0.3 mL solution of each material were started at 4 weeks postoperatively for a total of 5 weekly injections. Seventy knees were divided into the following groups: AL430 (430 kDa molecular weight UPLE alginate), AL1000 (1,000 kDa), AL1700 (1,700 kDa), HA (hyaluronan), and NS (normal saline). At 9 weeks postoperatively, all knees were assessed macroscopically, histologically, and mechanically.Results:Macroscopically, the UPLE alginate groups exhibited milder cartilage degradation compared to that of the NS and HA groups. Histological findings of the UPLE alginate groups showed an obvious reduction in the severity of OA. The histological scores of Kikuchi et al. were superior in the alginate treatment groups compared to the NS group. The friction coefficient of the AL1000 group was significantly lower than that of the NS and HA groups.Conclusion:This study indicates that our UPLE alginates, especially AL1000, have promising potential as an effective agent in preventing OA progression.