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Fibrin hydrogel based bone substitute tethered with BMP-2 and BMP-2/7 heterodimers

Karfeld-Sulzer, Lindsay; Siegenthaler, Barbara; Ghayor, Chafik; Weber, Franz E (2015). Fibrin hydrogel based bone substitute tethered with BMP-2 and BMP-2/7 heterodimers. Materials, 8(3):977-991.

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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Dental Medicine > Clinic of Cranio-Maxillofacial Surgery
04 Faculty of Medicine > Zurich Center for Integrative Human Physiology (ZIHP)
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Physical Sciences > General Materials Science
Uncontrolled Keywords:fibrin hydrogel, bone morphogenetic proteins, bone regeneration, bone substitute
Language:English
Date:2015
Deposited On:07 Jan 2016 12:44
Last Modified:10 Nov 2024 04:42
Publisher:MDPI Publishing
ISSN:1996-1944
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.3390/ma8030977
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  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

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