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Bisphosphonate Functionalized Gadolinium Oxide Nanoparticles Allow Long-Term MRI/CT Multimodal Imaging of Calcium Phosphate Bone Cement

Mastrogiacomo, Simone; Kownacka, Alicja E.; Dou, Weiqiang; Burke, Benjamin P.; de Rosales, Rafael T.M.; Heerschap, Arend; Jansen, John A.; Archibald, Stephen J.; Walboomers, X. Frank


Simone Mastrogiacomo

Alicja E. Kownacka

Weiqiang Dou

Benjamin P. Burke

Rafael T.M. de Rosales

Arend Heerschap

John A. Jansen

X. Frank Walboomers


Direct in vivo monitoring of bioconstructs using noninvasive imaging modalities such as magnetic resonance imaging (MRI) or computed tomography (CT) is not possible for many materials. Calcium phosphate–based composites (CPCs) that are applicable to bone regeneration are an example where the materials have poor MRI and CT contrast; hence, they are challenging to detect in vivo. In this study, a CPC construct is designed with gadolinium-oxide nanoparticles incorporated to act as an MRI/CT multimodal contrast agent. The gadolinium(III) oxide nanoparticles are synthesized via the polyol method and surface functionalized with a bisphosphonate (BP) derivative to give a construct (gadolinium-based contrast agents (GBCAs)-BP) with strong affinity toward calcium phosphate. The CPC-GBCAs-BP functional material is longitudinally monitored after in vivo implantation in a condyle defect rat model. The synthetic method developed produces nanoparticles that are stable in aqueous solution (hydrodynamic diameter 70 nm) with significant T1and T2relaxivity demonstrated in both clinical 3 T and preclinical 11.7 T MRI systems. The combination of GBCAs-BP nanoparticles with CPC gives an injectable material with handling properties that are suitable for clinical applications. The BP functionalization prolongs the residence of the contrast agent within the CPC to allow long-term follow-up imaging studies. The useful contrast agent properties combined with biological compatibility indicate further investigation of the novel bone substitute hybrid material toward clinical application.


Mastrogiacomo, S., Kownacka, A. E., Dou, W., Burke, B. P., de Rosales, R. T., Heerschap, A., …Walboomers, X. F. (2018). Bisphosphonate Functionalized Gadolinium Oxide Nanoparticles Allow Long-Term MRI/CT Multimodal Imaging of Calcium Phosphate Bone Cement. Advanced Healthcare Materials, 7(19), Article 1800202.

Journal Article Type Article
Online Publication Date Aug 17, 2018
Publication Date Oct 10, 2018
Deposit Date Dec 10, 2020
Publicly Available Date Oct 27, 2022
Journal Advanced Healthcare Materials
Print ISSN 2192-2640
Electronic ISSN 2192-2659
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 7
Issue 19
Article Number 1800202
Keywords Biphosphonate; Calcium phosphate cements; Computed tomography; Gadoliniumā€based contrast agents; Magnetic resonance imaging
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Copyright Statement
© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and repro-duction in any medium, provided the original work is properly cited

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