Real-Time Tracking of In Situ-Forming Alginate Hydrogel by Contrast-Enhanced Computed Tomography

Hydrogel-based biomaterials have gained broad acceptance for tissue engineering and drug delivery applications. As their function generally depends on their localization, identifying the hydrogel position in the body is relevant and will alert physicians about potentially dangerous hydrogel migration. Monitoring the localization of hydrogels by imaging is challenging due to their high water content. Here, we developed a method to render alginate hydrogels visible on computed tomography (CT) and X-ray for real-time tracking of hydrogels inside the body. This method is based on physically immobilizing emulsion droplets of ethiodized oil, an FDA-approved positive CT contrast agent, in calcium-crosslinked alginate hydrogels. We prepared an oil-in-water emulsion of ethiodized oil with micron-sized emulsion droplets and encapsulated it in a calcium-crosslinked alginate hydrogel. This injectable in situ-forming hydrogel was stable for at least 2 weeks in vitro, visible on CT and X-ray in mice, and showed contrast agent concentration-dependent signal intensities. Hydrogels retrieved from mice after imaging had suitable rheological properties with a storage modulus of about 2 kPa and a loss modulus of about 0.35 kPa. This proof-of-concept study highlights the potential of ethiodized oil to localize hydrogels in real time inside the body and identifies a new use of this FDA-approved contrast agent.