Monitoring implantable immunoisolation devices with intrinsic fluorescence of genipin

Imaging of implanted hydrogel-based biosystems usually requires indirect labeling of the vehicle or cargo, adding complexity and potential risk of altering functionality. Here, for the first time, it is reported that incorporation of genipin into the design of immunoisolation devices can be harnessed for in vivo imaging. Using cell-compatible in situ cross-linking reactions, a fast, efficient and noncytotoxic procedure is shown to maximize fluorescence of microcapsules. Moreover, genipin is validated as a quantitative imaging probe by injecting increasing doses of microcapsules in the subcutaneous space of mice, obtaining strong, stable fluorescence with good linearity of signal to microcapsule dose over several weeks. This allows immediate assessment of the actual injected dose and monitoring of its position over time, thereby significantly enhancing the efficacy and biosafety of the therapy. These outcomes may facilitate clinical translation and optimize medical applications of multiple hydrogel-based biotechnologies.