Microwave-assisted synthesis of TEMPO-labeled hydrogels traceable with MRI

Polymer functionalization strategies have recently attracted relevant attention for several applications in biomaterials science. In particular, technological advancements in medical imaging has focused on the design of polymeric matrices to improve non-invasive approaches and the diagnostic accuracy. In this scenario, the use of microwave irradiation of aqueous solutions containing appropriate combinations of polymers is gaining increasing interests in the synthesis of sterile hydrogels without using monomers, eliminating the need to remove unreacted species. In this study we developed a method for in situ fabrication of TEMPO-labeled hydrogel based on one pot microwave reaction that can then be tracked by magnetic resonance imaging (MRI) without using toxic compounds that could be hostile for the target tissue. Click chemistry was used to link TEMPO to the polymeric scaffold. In in vivo model, the system was able to preserve the TEMPO paramagnetic activity until 1 month after the hydrogel injection, showing a clear detectable signal on T1-weighted MRI with a longitudinal relaxivity value of 0.29 mM s-1, comparable to the value of 0.31 mM s-1 characteristic of TEMPO application. The uncleavable conjugation between the contrast agent and the polymeric scaffold is a leading point to record these results: the use of TEMPO only physically entrapped in polymeric scaffold did not show MRI traceability already after few hours. Moreover, the use of TEMPO-labeled hydrogels can also help to reduce the amount of animals sacrificed being a longitudinal non-invasive technique.