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Materials 2015, 8(3), 977-991; doi:10.3390/ma8030977

Fibrin Hydrogel Based Bone Substitute Tethered with BMP-2 and BMP-2/7 Heterodimers

1
Oral Biotechnology & Bioengineering, University Hospital, Division of Cranio-Maxillofacial and Oral Surgery and Center for Dental Medicine, University of Zurich, Plattenstrasse 11, Zurich CH-8032, Switzerland
2
Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich CH-8006, Switzerland
3
CABMM, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich CH-8006, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editor: Aldo R. Boccaccini
Received: 6 January 2015 / Revised: 9 February 2015 / Accepted: 2 March 2015 / Published: 6 March 2015
(This article belongs to the Special Issue Novel Bone Substitute Materials)
View Full-Text   |   Download PDF [767 KB, uploaded 6 March 2015]   |  

Abstract

Current clinically used delivery methods for bone morphogenetic proteins (BMPs) are collagen based and require large concentrations that can lead to dangerous side effects. Fibrin hydrogels can serve as osteoinductive bone substitute materials in non-load bearing bone defects in combination with BMPs. Two strategies to even further optimize such a fibrin based system include employing more potent BMP heterodimers and engineering growth factors that can be covalently tethered to and slowly released from a fibrin matrix. Here we present an engineered BMP-2/BMP-7 heterodimer where an N-terminal transglutaminase substrate domain in the BMP-2 portion provides covalent attachment to fibrin together with a central plasmin substrate domain, a cleavage site for local release of the attached BMP-2/BMP-7 heterodimer under the influence of cell-activated plasmin. In vitro and in vivo results revealed that the engineered BMP-2/BMP-7 heterodimer induces significantly more alkaline phosphatase activity in pluripotent cells and bone formation in a rat calvarial model than the engineered BMP-2 homodimer. Therefore, the engineered BMP-2/BMP-7 heterodimer could be used to reduce the amount of BMP needed for clinical effect. View Full-Text
Keywords: fibrin hydrogel; bone morphogenetic proteins; bone regeneration; bone substitute fibrin hydrogel; bone morphogenetic proteins; bone regeneration; bone substitute
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Karfeld-Sulzer, L.S.; Siegenthaler, B.; Ghayor, C.; Weber, F.E. Fibrin Hydrogel Based Bone Substitute Tethered with BMP-2 and BMP-2/7 Heterodimers. Materials 2015, 8, 977-991.

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