title: Characterization of recombinant human bone morphogenetic protein-2 delivery from injectable hyaluronan-based hydrogels by means of 125I-radiolabelling.
abstract: This study presents a thorough in vitro and in vivo characterization of the delivery of bone morphogenetic protein 2 (BMP-2) from a hyaluronan-based hydrogel system. The in vitro release of BMP-2 from similar hydrogels has previously been studied by enzyme-linked immunosorbent assay (ELISA), by which only a fraction of the loaded protein is detected. In the current study, (125) I radiolabelling was used instead to monitor BMP-2 in vitro and in vivo. To minimize protein loss during handling, (125) I-BMP-2 adsorption to different tubes was studied at different times and temperatures. The data showed that Protein LoBind tubes exhibited the lowest protein affinity. Furthermore, a biphasic release profile of biologically active BMP-2 was observed both in vitro and in vivo, with the initial fast phase during the first week, followed by a slower release during the remaining 3 weeks. The initial fast-release phase corresponded to the early bone formation observed after 8 days in an ectopic model in rats. Bone volume and mineral content increased until day 14, after which a decrease in bone volume was observed, possibly due to resorption in response to decreased amounts of released BMP-2. Overall, the results suggested that cautious protein handling and a reliable quantification technique are essential factors for successful design of a BMP-2 delivery system.
authors.affiliation: Department of Materials Chemistry, Uppsala University, Sweden.
authors.forename: Sonya
authors.initials: S
authors.lastname: Piskounova
authors.forename: Lars
authors.initials: L
authors.lastname: Gedda
authors.forename: Gry
authors.initials: G
authors.lastname: Hulsart-Billström
authors.forename: Jöns
authors.initials: J
authors.lastname: Hilborn
authors.forename: Tim
authors.initials: T
authors.lastname: Bowden
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006820:Hyaluronic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000494:pharmacology; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D055675:Viscosupplements
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D055675:Viscosupplements; D006820:Hyaluronic Acid