Visualization and Evaluation of Chemoembolization on a 3D Decellularized Organ Scaffold.

Abstract

Transarterial chemoembolization (TACE) has emerged as the mainstay treatment for patients suffering from unresectable intermediate hepatocellular carcinoma and also holds the potential to treat other types of hypervascular cancers such as renal cell carcinoma. However, an in vitro model for evaluating both embolic performance and drug-release kinetics of the TACE embolic agents is still lacking since the current models greatly simplified the in vivo vascular systems as well as the extracellular matrices (ECM) in the organs. Here, we developed a decellularized organ model with preserved ECM and vasculatures as well as a translucent appearance to investigate chemoembolization performances of a clinically widely used embolic agent, i.e., a doxorubicin-loaded ethiodised oil (EO)-based emulsion. We, for the first time, utilized an ex vivo model to evaluate the liquid-based embolic agent in two organs, i.e., liver and kidneys. We found that the EO-based emulsion with enhanced stability by incorporating an emulsifier, i.e., hydrogenated castor oil-40 (HCO), showed an enhanced occlusion level and presented sustained drug release in the ex vivo liver model, suggesting an advantageous therapeutic effect for TACE treatment of hepatocellular carcinoma. In contrast, we observed that drug-release burst happened when applying the same therapy in the kidney model even with the HCO emulsifier, which may be explained by the presence of the specific renal vasculature and calyceal systems, indicating an unfavorable effect in the renal tumor treatment. Such an ex vivo model presents a promising template for chemoembolization evaluation before in vivo experiments for the development of novel embolic agents.