IN-VITRO CHARACTERIZATION AND IN-VIVO EFFICACY OF A PROSTAGLANDIN-E(2) POLY(ORTHO ESTER) IMPLANT FOR BONE-GROWTH PROMOTION

Prostaglandin E2 (PGE2) is a known stimulator of bone growth, yet when systemically administered at efficacious levels there are serious side effects. It was hypothesized that local delivery of a low dose of PGE, would increase the rate of bone growth without systemic side effects. Biodegradable poly(ortho ester) (P(OE)) implants (4 mg, diameter= 2 mm, height = 1 mm) containing three different loadings of PGE2 (0.81, 0.035 or 0.0032% PGE2 w/w) were fabricated, characterized for in vitro release, and implanted in vivo in rat tibiae for 8 days. The PGE, release rate in vitro increased with increased initial loading of PGE2; this increase was faster than predicted by a diffusional matrix release mechanism and was consistent with acid catalyzed P(OE) degradation in response to the PGE2. In vivo, bone was examined at the end of the 8 day implantation period for new growth. These studies showed that the implants with the two highest loadings significantly enhanced (up to 3-fold) localized bone growth with no observable side effects in any of the treatment groups. This approach may be useful for enhancing bone growth in clinical situations which require bone augmentation or repair.