title: 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.
authors.affiliation: Bone Biology and Applications, Genetics Institute, Andover, Massachusetts 01810, USA.
authors.forename: H
authors.initials: H
authors.lastname: Uludag
authors.forename: D
authors.initials: D
authors.lastname: D'Augusta
authors.forename: R
authors.initials: R
authors.lastname: Palmer
authors.forename: G
authors.initials: G
authors.lastname: Timony
authors.forename: J
authors.initials: J
authors.lastname: Wozney
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001846:Bone Development / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001842:Bone and Bones / Q000166:cytology; D016466:CHO Cells; D003094:Collagen; D006224:Cricetinae; D004337:Drug Carriers; D004343:Drug Implants; D006207:Half-Life; D006801:Humans; D007457:Iodine Radioisotopes; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D013462:Sulfur Radioisotopes; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D004343:Drug Implants; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D013462:Sulfur Radioisotopes; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen