CT-VISIBLE MICROSPHERES ENABLE IN VIVO TRACKING OF BIOMATERIAL DISTRIBUTION AFTER ULTRASOUND-GUIDED INTRAMYOCARDIAL INJECTION

Efficacy of cell therapies are often diminished by low cell retention. A method to visualise the location of grafted cells and biomaterials after delivery could be used to optimise therapies by verifying injection success, retention of the therapeutic and distribution of the product. To address these challenges an injectable cell-substrate consisting of highly porous microspheres containing the computed tomography (CT) contrast agent barium sulphate (BaSO4) was developed.Porous microspheres (<250 µm) were fabricated via Thermally Induced Phase Separation (TIPS) using a 2% (w/v) 75:25 poly(DL-lactide-co-glycolide) polymer solution containing a 20% (w/v) colloidal suspension of particulate BaSO4. Culture media conditioned with BaSO4-loaded microspheres (46.87 mg/ml) showed no significant toxicity when cultured with L929 fibroblasts for up to 7 days (maximum toxicity 12% vs 5% matched control media, n=4, p<0.01). Suspensions of BaSO4-loaded microspheres generated high CT contrast in vitro (average 2023.6 Hounsfield Units ±710 SD) (figure 1A) and were then tested in vivo. Three 50 µl injections of BaSO4-loaded microspheres (46.87 mg/ml in 60% GRANUGEL®; 21G needle) were delivered into the myocardium of Sprague Dawley rats under real-time ultrasound-guidance (n=6). Whole body CT scans revealed BaSO4-loaded microspheres at the injection site within the myocardium at 1 hour, 2, 4 and 6 days after injection (figure 1B and 1C). These findings were confirmed by histology (figure 1D). A low level of microspheres was visualised in off-target organs including lung, brain and liver, indicating some material was lost during injection. 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 products. Conflict of Interest None