Characterization of rhBMP-2 pharmacokinetics implanted with biomaterial carriers in the rat ectopic model

Abstract

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a member of the bone morphogenetic protein family involved in de novo bone induction. Successful use of rhBMP-2 requires implantation with a biomaterial which can act as a scaffold for cell invasion for osteoinduction and retains rhBMP-2 at a site of implantation. This study was carried out to characterize rhBMP-2 pharmacokinetics from a variety of biomaterial carriers in a rat ectopic model. Retention of rhBMP-2 within carriers after 3 h was variable among the carriers (range, 75-10%), with collagenous sponges retaining the highest fraction of implanted dose. A gradual loss of rhBMP-2 was subsequently observed, the kinetics of which was strongly dependent on the implanted carrier. Collagenous carriers were observed to lose rhBMP-2 gradually from the implant site, whereas some of the mineral-based carriers retained a fraction of implanted rhBMP-2 within the implants. These differences in protein pharmacokinetics among carriers, in addition to their physicochemical nature, are expected to affect the biological activity of implanted rhBMP-2.