LOCAL-DELIVERY OF INDOMETHACIN BY A POLYORTHOESTER INHIBITS REOSSIFICATION OF EXPERIMENTAL BONE DEFECTS

Inhibition of orthotopic reossification after surgical removal of bone is sometimes indicated and may be accomplished by implantation of int erpositional materials or by systemic administration of indomethacin. However, implantation of nonresorbable foreign material may induce a c hronic inflammation and predispose to infections; and systemic adminis tration of indomethacin may induce systemic adverse effects. We studie d the effect of local delivery of indomethacin by a bioerodible polyor thoester on the reossification of segmental defects of the radius in r ats. We divided 45 Wistar rats into three groups, A-C. A 3.5 mm-long m iddiaphyseal osteoperiosteal resection of the right radius was made in each rat. The defect was filled with 15 mg of polyorthoester with 5% indomethacin in group A and 15 mg of polyorthoester without drug in gr oup B. No material was implanted in the defects in the group C rats. T he rats were killed 50 days postoperatively. The mean area of the resi dual defects were greater in the defects with the polyorthoester with 5% indomethacin compared with defects with polyorthoester without drug or without implant as judged by computer-assisted area measurements o n radiographs. By light microscopy, no inflammation was seen and only traces of the polyorthoester could be detected in the defects filled w ith the polyorthoester with or without indomethacin. The results of th is study suggest that the polyorthoester may be used as a bioerodible system for local delivery of indomethacin to inhibit reossification of skeletal defects without tissue reaction, unabsorbed carrier, or syst emic effects. (C) 1995 John Wiley and Sons, Inc.