title: BMP-2 delivered via sucrose acetate isobutyrate (SAIB) improves bone repair in a rat open fracture model.
abstract: Human bone morphogenetic proteins (BMPs) are an alternative to bone graft for the treatment of high-energy open fractures. The standard delivery system for BMP-2 is a porous collagen sponge, but we have previously found that the biocompatible, high viscosity carrier, Sucrose acetate isobutyrate (SAIB) is an effective and potentially less invasive alternative. The efficacy of SAIB as a BMP-2 delivery system was examined in an open fracture model featuring a femoral osteotomy with periosteal stripping in 9-week-old male Sprague Dawley rats. SAIB containing BMP-2 (SAIB/BMP-2) was delivered into the fracture site during surgery and an additional group was further co-treated with zoledronic acid and hydroxyapatite nanoparticles (SAIB/BMP-2/HA/ZA). These were compared to untreated fractures and SAIB carrier alone (negative controls), and BMP-2 loaded collagen sponge (positive control). The rate of radiographic union and the biomechanical properties of the healed fractures were compared after 6-week. Untreated and SAIB-treated fractures showed poor repair, with 53% and 64%, respectively, not bridged at 6 week. In contrast, collagen/BMP-2, SAIB/BMP-2, and SAIB/BMP-2/HA/ZA showed significantly increased union (100%, 100%, and 94%, respectively, p < 0.05). Four-point bend testing revealed that collagen/BMP-2 and SAIB/BMP-2/HA/ZA restored the strength of fractured femora to that of intact femora by 6 week, whereas untreated and SAIB remained less than intact controls by 60% and 67%, respectively (p < 0.05). Overall, the SAIB/BMP-2/HA/ZA formulation was comparable to BMP-2 infused collagen sponge in terms of promoting open fractures repair, but with the additional potential for less invasive delivery. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1168-1176, 2016.
authors.affiliation: Orthopaedic Research and Biotechnology Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, Sydney, New South Wales, 2145, Australia.|Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Tegan L
authors.initials: TL
authors.lastname: Cheng
authors.affiliation: Orthopaedic Research and Biotechnology Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, Sydney, New South Wales, 2145, Australia.|Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Aaron
authors.initials: A
authors.lastname: Schindeler
authors.affiliation: Orthopaedic Research and Biotechnology Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, Sydney, New South Wales, 2145, Australia.|Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: David G
authors.initials: DG
authors.lastname: Little
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D016723:Bone Remodeling / Q000187:drug effects; D002146:Bony Callus / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D017102:Fracture Healing / Q000187:drug effects*; D005597:Fractures, Open / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000031:analogs & derivatives; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D013395:Sucrose; C002885:sucrose acetate isobutyrate
keywords: BMP-2; SAIB; ZA; bone tissue engineering; nonunion; open fracture