CT‐Visible Microspheres Enable Whole‐Body In Vivo Tracking of Injectable Tissue Engineering Scaffolds

Targeted delivery and retention are essential requirements for implantable tissue‐engineered products. Non‐invasive imaging methods that can confirm location, retention, and biodistribution of transplanted cells attached to implanted tissue engineering scaffolds will be invaluable for the optimization and enhancement of regenerative therapies. To address this need, an injectable tissue engineering scaffold consisting of highly porous microspheres compatible with transplantation of cells is modified to contain the computed tomography (CT) contrast agent barium sulphate (BaSO4). The trackable microspheres show high x‐ray absorption, with contrast permitting whole‐body tracking. The microspheres are cellularized with GFP+ Luciferase+ mesenchymal stem cells and show in vitro biocompatibility. In vivo, cellularized BaSO4‐loaded microspheres are delivered into the hindlimb of mice where they remain viable for 14 days. Co‐registration of 3D‐bioluminescent imaging and µCT reconstructions enable the assessment of scaffold material and cell co‐localization. The trackable microspheres are also compatible with minimally‐invasive delivery by ultrasound‐guided transthoracic intramyocardial injections in rats. These findings suggest that BaSO4‐loaded microspheres can be used as a novel tool for optimizing delivery techniques and tracking persistence and distribution of implanted scaffold materials. Additionally, the microspheres can be cellularized and have the potential to be developed into an injectable tissue‐engineered combination product for cardiac regeneration. Highly porous microspheres containing barium sulfate are produced and then cellularized with bioluminescent mesenchymal stem cells to permit detection using X‐ray CT and optical imaging. Injectable microspheres are delivered in a minimally invasive manner under ultrasound guidance. This multi‐modal imaging approach allows co‐localization of cells and microspheres that can be studied longitudinally in vivo.