Monitoring tissue implants by field-cycling H-1-MRI via the detection of changes in the N-14-quadrupolar-peak from imidazole moieties incorporated in a "smart" scaffold material

Valeria Bitonto, Enza Di Gregorio, Simona Baroni, Rachele Stefania, Silvio Aime, Lionel Broche, Nicholas Senn, James Ross, David Lurie, Simonetta Geninatti Crich* (Corresponding Author)

*Corresponding author for this work

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This study is focused on the development of innovative sensors to non-invasively monitor the tissue implant status by Fast-Field-Cycling Magnetic Resonance Imaging (FFC-MRI). These sensors are based on oligo-histidine moieties that are conjugated to PLGA polymers representing the structural matrix for cells hosting scaffolds. The presence of 14N atoms of histidine causes a quadrupolar relaxation enhancement (also called Quadrupolar Peak, QP) at 1.39 MHz. This QP falls at a frequency well distinct from the QPs generated by endogenous semisolid proteins. The relaxation enhancement is pH dependent in the range 6.5-7.5, thus it acts as a reporter of the scaffold integrity as it progressively degrades upon lowering the microenvironmental pH. The ability of this new sensors to generate contrast in an image obtained at 1.39 MHz on a FFC-MRI scanner is assessed. A good biocompatibility of the histidine-containing scaffolds is observed after its surgical implantation in healthy mice. Over time the scaffold is colonized by endogenous fibroblasts and this process is accompanied by a progressive decrease of the intensity of the relaxation peak. In respect to the clinically used contrast agents this material has the advantage of generating contrast without the use of potentially toxic paramagnetic metal ions.
Original languageEnglish
Pages (from-to)4863-4872
Number of pages10
JournalJournal of Materials Chemistry B
Issue number24
Early online date1 Jun 2021
Publication statusPublished - 28 Jun 2021

Bibliographical note

This work was performed in the frame of the COST Action AC15209 (EURELAX). The
authors acknowledge the Italian Ministry of Research for FOE contribution to the EuroBioImaging MultiModal Molecular Imaging Italian Node ( This project has received funding from the European Union Horizon 2020 research and innovation program under grant agreement No 668119 (project “IDentIFY”) and from the ATTRACT project funded by the EC under Grant Agreement No. 777222.

Data Availability Statement

All data analysed during this study are included in this published article (and its ESI† file). Other raw data required to reproduce these findings are available from the corresponding author on reasonable request.


  • biomaterial for tissue engineering
  • fast field-cycling magnetic resonance imaging (FFC-MRI)
  • quadrupole peaks
  • imaging probes
  • regenerative medicine
  • Biomedical Engineering
  • General Chemistry
  • General Medicine
  • General Materials Science


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