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

Abstract

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.

Citation

Mastrogiacomo, S., Kownacka, A. E., Dou, W., Burke, B. P., de Rosales, R. T., Heerschap, A., Jansen, J. A., Archibald, S. J., & 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. https://doi.org/10.1002/adhm.201800202

• Journal Article Type: Article
• Online Publication Date: Aug 17, 2018
• Publication Date: Oct 10, 2018
• Deposit Date: Dec 10, 2020
• Publicly Available Date: Feb 19, 2021
• Journal: Advanced Healthcare Materials
• Print ISSN: 2192-2640
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 19
• Article Number: 1800202
• DOI: https://doi.org/10.1002/adhm.201800202
• Keywords: Biphosphonate; Calcium phosphate cements; Computed tomography; Gadolinium‐based contrast agents; Magnetic resonance imaging
• Public URL: https://hull-repository.worktribe.com/output/1022308