Protein Polymer MRI Contrast Agents: Longitudinal Analysis of Biomaterials in Vivo

Despite recent advances in tissue engineering to regenerate biological function by combining cells with material supports, development is hindered by inadequate techniques for characterizing biomaterials in vivo. Magnetic Resonance Imaging (MRI) is a tomographic technique with high temporal and spatial resolution and represents an excellent imaging modality for longitudinal non-invasive assessment of biomaterials in vivo. To distinguish biomaterials from surrounding tissues for MR imaging, protein polymer contrast agents (PPCAs) were developed and incorporated into hydrogels. In vitro and in vivo images of protein polymer hydrogels, with and without covalently incorporated PPCAs, were acquired by MRI. T1 values of the labeled gels were consistently lower when PPCAs were included. As a result, the PPCA hydrogels facilitated fate tracking, quantification of degradation, and detection of immune response in vivo. For the duration of the in vivo study, the PPCA-containing hydrogels could be distinguished from adjacent tissues and from the foreign body response surrounding the gels. The hydrogels containing PPCA have a contrast-to-noise ratio two-fold greater than hydrogels without PPCA. In the absence of the PPCA, hydrogels cannot be distinguished by the end of the gel lifetime.