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

Abstract

Targeted delivery and retention is an essential requirement 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 would be invaluable for the optimisation and enhancement of regenerative therapies. To address this need, an injectable tissue engineering scaffold consisting of highly porous microspheres compatible with transplantation of cells was modified to contain the computed tomography (CT) contrast agent barium sulphate (BaSO4). The trackable microspheres showed high x‐ray absorption, with contrast permitting whole‐body tracking. The microspheres were cellularised with GFP+ Luciferase+ mesenchymal stem cells and showed in vitro biocompatibility. In vivo, cellularised BaSO4‐loaded microspheres were delivered into the hindlimb of mice where they remained viable for 14 days. Co‐registration of 3D‐BLI and μCT reconstructions enabled assessment of scaffold material and cell co‐localization. The trackable microspheres were 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 optimising delivery techniques and tracking persistence and distribution of implanted scaffold materials. Additionally, the microspheres can be cellularised and have the potential to be developed into an injectable tissue engineered combination product for cardiac regeneration.This article is protected by copyright. All rights reserved