Local delivery of indomethacin by a polyorthoester inhibits resossification of experimental bone defects

Abstract

Inhibition of orthotopic reossification after surgical removal of bone is sometimes indicated and may be accomplished by implantation of interpositional materials or by systemic administration of indomethacin. However, implantation of nonresorbable foreign material may induce a chronic inflammation and predispose to infections; and systemic administration of indomethacin may induce systemic adverse effects. We studied the effect of local delivery of indomethacin by a bioerodible polyorthoester on the reossification of segmental defects of the radius in rats. We divided 45 Wistar rats into three groups, A-C. A 3.5 mm-long middiaphyseal 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 group B. No material was implanted in the defects in the group C rats. The rats were killed 50 days postoperatively. The mean area of the residual 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 on radiographs. By light microscopy, no inflammation was seen and only traces of the polyorthoester could be detected in the defects filled with the polyorthoester with or without indomethacin. The results of this 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 systemic effects.