Injectable hyaluronic acid hydrogels with the capacity for magnetic resonance imaging.

Monitoring hydrogel degradation in real time using noninvasive imaging techniques is of great interest for designing a scaffold in tissue engineering. We report the preparation of gadolinium (Gd)-labeled and injectable hyaluronic acid (HA) hydrogels that can be visualized using T- and T-weighted magnetic resonance imaging (MRI). An HA derivative functionalized with thiol and hydrazide was labeled using a diethylenetriaminepentaacetate complex modified with "clickable" dithiopyridyl functionalities (degree of modification was 3.77% with respect to HA repeat units). The HA derivative modified with cross-linkable groups and Gd complex exhibited relaxivities r = 3.78 mMs and r = 56.3 mMs. A hydrazone hydrogel network was obtained by mixing Gd-labeled HA-hydrazide and HA-aldehyde derivatives. Enzymatic hydrogel degradation could be followed using MRI because the MR images showed great correlation with the hydrogel mass loss. Ex vivo MRI of injected Gd-labeled hydrogels demonstrated that they show a significant contrast difference (SNR = 456; SNR = 459) from the surrounding tissues. These results indicate that our Gd-labeled HA hydrogel has great potential as an injectable biocompatible hydrogel that can be used for longitudinal tracking in vivo using MRI.