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A theranostic agent to enhance osteogenic and magnetic resonance imaging properties of calcium phosphate cements
Authors:Manuela Ventura  Yi Sun  Sjef Cremers  Paul Borm  Zeinab T Birgani  Pamela Habibovic  Arend Heerschap  Peter M van der Kraan  John A Jansen  X Frank Walboomers
Institution:1. Department of Biomaterials, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands;2. Department of Radiology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands;3. Department of Urology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands;4. Nano4Imaging GmbH, Zentrum für Biomedizintechnik (ZBMT), Pauwelsstrasse 17, 52074 Aachen, Germany;5. Department of Tissue Regeneration, University of Twente, MIRA Institute for Biomedical Technology and Technical Medicine, PO Box 217, 7500 AE Enschede, The Netherlands;6. Department of Rheumatology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
Abstract:With biomimetic biomaterials, like calcium phosphate cements (CPCs), non-invasive assessment of tissue regeneration is challenging. This study describes a theranostic agent (TA) to simultaneously enhance both imaging and osteogenic properties of such a bone substitute material. For this purpose, mesoporous silica beads were produced containing an iron oxide core to enhance bone magnetic resonance (MR) contrast. The same beads were functionalized with silane linkers to immobilize the osteoinductive protein BMP-2, and finally received a calcium phosphate coating, before being embedded in the CPC. Both in vitro and in vivo tests were performed. In vitro testing showed that the TA beads did not interfere with essential material properties like cement setting. Furthermore, bioactive BMP-2 could be efficiently released from the carrier-beads. In vivo testing in a femoral condyle defect rat model showed long-term MR contrast enhancement, as well as improved osteogenic capacity. Moreover, the TA was released during CPC degradation and was not incorporated into the newly formed bone. In conclusion, the described TA was shown to be suitable for longitudinal material degradation and bone healing studies.
Keywords:Bone tissue engineering  Calcium phosphate cement  BMP (bone morphogenetic protein)  Drug delivery  MRI (magnetic resonance imaging)
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