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01.03.2014 | Review Article

The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing

verfasst von: Slobodan Vukicevic, Hermann Oppermann, Donatella Verbanac, Morana Jankolija, Irena Popek, Jasna Curak, Jelena Brkljacic, Martina Pauk, Igor Erjavec, Igor Francetic, Ivo Dumic-Cule, Mislav Jelic, Dragan Durdevic, Tomislav Vlahovic, Ruder Novak, Vera Kufner, Tatjana Bordukalo Niksic, Marija Kozlovic, Zrinka Banic Tomisic, Jadranka Bubic-Spoljar, Ivancica Bastalic, Smiljka Vikic-Topic, Mihaela Peric, Marko Pecina, Lovorka Grgurevic

Erschienen in: International Orthopaedics | Ausgabe 3/2014

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Abstract

Purpose

The purpose of this study was to revise the clinical use of commercial BMP2 (Infuse) and BMP7 (Osigraft) based bone devices and explore the mechanism of action and efficacy of low BMP6 doses in a novel whole blood biocompatible device OSTEOGROW.

Methods

Complications from the clinical use of BMP2 and BMP7 have been systemically reviewed in light of their role in bone remodeling. BMP6 function has been assessed in Bmp6-/- mice by μCT and skeletal histology, and has also been examined in mesenchymal stem cells (MSC), hematopoietic stem cells (HSC) and osteoclasts. Safety and efficacy of OSTEOGROW have been assessed in rats and rabbits.

Results

Clinical use issues of BMP2 and BMP7 have been ascribed to the limited understanding of their role in bone remodeling at the time of device development for clinical trials. BMP2 and BMP7 in bone devices significantly promote bone resorption leading to osteolysis at the endosteal surfaces, while in parallel stimulating exuberant bone formation in surrounding tissues. Unbound BMP2 and BMP7 in bone devices precipitate on the bovine collagen and cause inflammation and swelling. OSTEOGROW required small amounts of BMP6, applied in a biocompatible blood coagulum carrier, for stimulating differentiation of MSCs and accelerated healing of critical size bone defects in animals, without bone resorption and inflammation. BMP6 decreased the number of osteoclasts derived from HSC, while BMP2 and BMP7 increased their number.

Conclusions

Current issues and challenges with commercial bone devices may be resolved by using novel BMP6 biocompatible device OSTEOGROW, which will be clinically tested in metaphyseal bone fractures, compartments where BMP2 and BMP7 have not been effective.

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Titel: The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing
verfasst von: Slobodan Vukicevic
Hermann Oppermann
Donatella Verbanac
Morana Jankolija
Irena Popek
Jasna Curak
Jelena Brkljacic
Martina Pauk
Igor Erjavec
Igor Francetic
Ivo Dumic-Cule
Mislav Jelic
Dragan Durdevic
Tomislav Vlahovic
Ruder Novak
Vera Kufner
Tatjana Bordukalo Niksic
Marija Kozlovic
Zrinka Banic Tomisic
Jadranka Bubic-Spoljar
Ivancica Bastalic
Smiljka Vikic-Topic
Mihaela Peric
Marko Pecina
Lovorka Grgurevic
Publikationsdatum: 01.03.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: International Orthopaedics / Ausgabe 3/2014
Print ISSN: 0341-2695
Elektronische ISSN: 1432-5195
DOI: https://doi.org/10.1007/s00264-013-2201-1

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