ECTS2013 Poster Presentations Bone development/growth and fracture repair (40 abstracts)
A novel biocompatible BMP6 carrier device for bone regeneration
Lovorka Grgurevic 1 , Igor Erjavec 1 , Morana Jankolija 2 , Irena Popek 2 , Anamarija Olic 2 , Smiljka Vikic Topic 3 , Donatella Verbanac 3 , Mihaela Peric 3 , Hermann Oppermann 2 & Slobodan Vukicevic 1
1Laboratory of Mineralized Tissues, School of Medicine, Center for Translational and Clinical Research, University of Zagreb, Zagreb, Croatia; 2Genera Research, Rakov Potok, Croatia; 3School of Medicine, Center for Translational and Clinical Research, University of Zagreb, Zagreb, Croatia.
Bone morphogenetic protein 6 (BMP6) is a member of TGF-β superfamily with a high potential to induce new bone and cartilage. Here we demonstrate that BMP6 compared to the BMP7 paralog has unique biological properties. Previously, we showed that BMP6 is more active at lower amounts then BMP7 because of increased resistance to noggin due to lysine in position 60. Next, we discovered that BMP6 binds to blood coagulum components, which when modified with calcium salt and a fibrin (WBCD) serve as a biocompatible BMP6 carrier for bone fracture repair. We confirmed by dot blot analysis specific binding affinity of BMP6 to components of blood coagulum including fibrinogen-like molecules. In vivo we proved that low amounts of BMP6 were two orders of magnitude more potent than BMP7 used in current commercial devices. In an animal model of critical size defect of rabbit ulnae we compared WBCD alone, the commercial device containing 1 g bovine collagen and 3.5 mg BMP7 (Osigraft), and WBCD containing 50 μg BMP6 for 8 weeks, and found that 50 μg BMP6 was more efficacious than 3.5 mg of BMP7. At 8 weeks, critical size ulna defect in rabbits treated with WBCD containing BMP6 fully rebridged the bone defect at a significantly accelerated rate than the commercial bone device. Recombinant human GMP produced BMP6 will be clinically investigated in indications for regeneration of the metaphyseal bone fracture repair which could not be achieved by BMP2 and BMP7 based bone devices. Development of the new bone device OSTEOGROW is supported by a seventh framework program (FP7).
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Bone Abstracts
ISSN 2052-1219 (online)
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