Iopamidol as MRI-CEST contrast agent for improved infection detection on mesoporous TiO2-functionalised biomedical implants

This work presents a novel approach for detecting infections on prosthetic implants via imaging, which is currently a crucial problem in the biomedical sector. For this purpose, a mesoporous titania layer (pore size ~6 nm) was produced via self-assembly of Titanium (IV) Butoxide and Pluronic P123 as templating agent. Its role is to coat a prosthetic device so as to guarantee a functionalised active surface, able to integrate correctly with human tissues as well as, most importantly, to carry a specific contrast agent for MRI in its pores. Iopamidol was selected as a drug for MRI-CEST, which would give birth to a signal that is promptly related to local pH changes in the tissues surrounding the prosthesis. This procedure would eventually result in pH-mapping the affected zone, thus helping the surgeon follow the clinical situation in a non-invasive manner. The produced layer was extensively characterised. SEM and TEM allowed concluding that our coating has a 200 nm thick disordered mesoporous structure. From BET average pore size is 5.7 nm, and the estimated lower bounds for specific volume and specific surface area are Vs = 0.031cm3g−1, and SABET = 21.32m2g−1 respectively. The long-range order and characteristic dimensions were further confirmed with SAXS and WAXS analysis. XRD detected minor crystalline traces ascribable to anatase. Lastly, loading/elution in cuvette and QCM-D highlighted the ability of the layer to uptake/release Iopamidol, showing good chemical affinity for the intended purpose. Finally, MRI-CEST was performed at different pH levels (from 5.5 to 7.4) in order to assess the responsiveness of Iopamidol as loaded in the pores of our samples. Although Iopamidol is a promising contrast agent for this application, both the difficulties encountered in the realisation of the experiment and the novelty of CEST set up open challenges for validating the concept. As for future perspectives, further characterisation with ex vivo and in vivo tests would strengthen this study.