title: The efficacy of bone morphogenetic protein-2 depends on its mode of delivery.
abstract: Bone morphogenetic protein-2 (BMP-2) induces bone regeneration in a dose-dependent manner, with higher doses of BMP-2 inducing greater bone formation. Previously, we showed that long-term delivery of BMP-2 provides better ectopic bone formation than short-term delivery of an equivalent dose. In the present study, we investigated the efficacy of orthotopic bone formation over a range of BMP-2 doses, using different delivery modes. Heparin-conjugated poly(lactic-co-glycolic acid) nanospheres suspended in fibrin gel were used as a long-term delivery system, and fibrin gel was used as a short-term delivery system. Different doses of BMP-2 were delivered to mouse calvarial defects using either long-term or short-term delivery systems. Eight weeks after treatment, bone regeneration was evaluated by histomorphometry. For both delivery systems, bone regeneration increased as the BMP-2 dose increased up to 1 µg and did not increase beyond this dose. Importantly, at BMP-2 doses higher than 1 µg, long-term delivery resulted in much greater bone formation than short-term delivery. This study shows that long-term delivery of BMP-2 is more effective at enhancing orthotopic bone formation than short-term delivery over a range of doses.
authors.affiliation: Seoul National University, Seoul, Republic of Korea.
authors.forename: Wan-Geun
authors.initials: WG
authors.lastname: La
authors.forename: Sun-Woong
authors.initials: SW
authors.lastname: Kang
authors.forename: Hee Seok
authors.initials: HS
authors.lastname: Yang
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Bhang
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry*; D005337:Fibrin / Q000737:chemistry; D005782:Gels / Q000737:chemistry; D006493:Heparin / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D054118:Nanospheres / Q000737:chemistry; D010012:Osteogenesis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012886:Skull / Q000187:drug effects / Q000473:pathology
chemical_list: D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D005782:Gels; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005337:Fibrin; D006493:Heparin