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

Area of Science:

• Biomedical Engineering
• Oncology
• Drug Delivery

Background:

• Transarterial chemoembolization (TACE) is a primary treatment for unresectable intermediate hepatocellular carcinoma and other hypervascular tumors.
• Existing in vitro models inadequately replicate the complex in vivo vascular systems and extracellular matrices (ECM) crucial for evaluating TACE agents.
• A need exists for advanced models to assess both the embolic performance and drug-release kinetics of TACE agents.

Purpose of the Study:

• To develop and validate a decellularized organ model for evaluating TACE embolic agents.
• To investigate the chemoembolization performance of a doxorubicin-loaded ethiodised oil (EO)-based emulsion in liver and kidney models.
• To assess the impact of an emulsifier (hydrogenated castor oil-40, HCO) on embolic agent stability and drug release.

Main Methods:

• Development of a translucent, decellularized organ model preserving native ECM and vasculature.
• Ex vivo evaluation of a doxorubicin-loaded EO-based emulsion, with and without HCO, in liver and kidney models.
• Assessment of embolic agent occlusion and drug-release profiles using the developed organ models.

Main Results:

• The HCO-stabilized EO emulsion demonstrated enhanced occlusion and sustained drug release in the ex vivo liver model, indicating potential for hepatocellular carcinoma treatment.
• Drug release burst was observed with the HCO-stabilized EO emulsion in the ex vivo kidney model, attributed to unique renal vasculature.
• The decellularized organ model successfully differentiated the performance of the embolic agent between liver and kidney environments.

Conclusions:

• The developed decellularized organ model provides a valuable platform for evaluating TACE agents ex vivo.
• The HCO-stabilized EO emulsion shows promise for TACE in liver cancer but requires modification for effective kidney cancer treatment.
• This model facilitates the preclinical assessment of novel embolic agents, potentially accelerating TACE therapy development.