The rapid development of  biotechnology has seen the dramatic increase in applications for  transparent models of organs for the observation and study of the  delicate three-dimensional structure of organs and mechanisms of  diseases. An international collaboration led by the Southern University  of Science and Technology (SUSTech) has made significant progress in the  construction of transparent liver organs modeling liver cancer  interventional treatments, providing significant help to researchers,  doctors, and patients.

    Assistant Professor Qiongyu Guo of Biomedical Engineering  at the SUSTech led her research team to work with the National  University of Singapore and Henan University to publish a paper in the  high-impact academic journal, Biomaterials (IF = 10.273). The article was titled “Decellularized liver as a translucent ex vivo model for vascular embolization evaluation.”

    Approximately 850,000 new cases of liver cancer are reported  worldwide annually. Liver cancer has placed a heavy burden on society in  many countries and is currently the leading cause of death for men  under 50 years of age. Hepatocellular carcinoma (HCC), which accounts  for 85%–90% of primary liver cancers, is the predominant pathological  type of malignant liver tumors.

    Transcatheter arterial chemoembolization (TACE), which applies  embolic agents to selectively occlude tumor-supplying hepatic arteries,  is currently the mainstay treatment for patients who have lost the  opportunity for resection surgery. However, there is not an adequate  model to evaluate embolization performance for TACE treatment, which has  affected the development of new embolotherapies.

    In vitro models such as microfluidics have been used to  evaluate the performance of these agents. However, the materials used in  the models do not correctly replicate the mechanical properties of  blood vessels. The model channels are often too simple to simulate the  complexities of HCC. The limited spatial resolution of X-ray-based  instruments available for TAE/TACE and the lack of imageability of most  solid embolic agents themselves prevent the accurate study of the  penetration depth and embolization endpoints in animal models. Thus, the  development of a new TACE model system that accurately evaluates  embolic agents is vital for this clinical field.

Figure 1. Quantitative analysis of the vascular systems of a translucent liver model

    The research group has proposed a new strategy for assessing vascular  embolization by using decellularized whole livers as a clearing in vitro  model. In recent years, decellularization has been used primarily for  regenerating organs. The team developed a transparent liver by applying a  strictly controlled decellularization perfusion method. They completely  removed the cells while maintaining the extracellular matrix and the  vascular system within the liver. The model of the liver was  translucent, allowing the vascular system to be viewed through a variety  of imaging tools (Figure 1).

Figure 2. Evaluation of different embolic agents in a cleared, isolated liver model

    The researchers successfully used the translucent model to evaluate  different types of embolic agents (Figure 2). They observed that the  embolization endpoint of a liquid embolic agent depends strongly on the  injection pressure and the location of the injection. Solid embolic  agents tend to have a reduced density near the end of an embolization  site. These findings confirm that particle size and penetration depth  are two key factors that determine embolic distribution.

Figure 3. Dynamic monitoring of embolization kinetics of liquid embolic agent iodized oil

    The research team also examined the embolization kinetics of TACE  treatment, and for the first time, evaluated the correlation between the  embolization pressure and the penetration depth as well as the liver  morphologies in the decellularized liver model (Figure 3). This model  enables the monitoring of the spatiotemporal location of embolic agents.  The finding is critical for real-time analyses of the effectiveness of  embolization formulations for TACE treatment.

    This research opens up new methods for developing transparent organ  models for visualization research and evaluation of clinical treatment  methods. It will provide more effective assessment strategies for the  translational research of various biotechnologies and biomaterials.

    SUSTech research assistant Yanan Gao is the first author of the paper with research assistant Zhihua Li has made vital contributions to the paper. Assistant Professor Qiongyu Guo  is the corresponding author of the article, and SUSTech is the first  communication unit. Additional contributions came from the National University of Singapore (Department of Biomedical Engineering, Yong Loo Lin School of Medicine, and Mechanobiology Institute), the First Affiliated Hospital of SUSTech (Shenzhen People’s Hospital), SUSTech (Materials Science and Engineering, Academy of Advanced Interdisciplinary Studies), Henan University (College of Medicine), A*STAR (Institute of Bioengineering and Nanotechnology), Singapore-MIT Alliance for Research and Technology (CAMP), and Southern Medical University (Gastroenterology Department).

    This research received support from the Key-Area Research and  Development Program of Guangdong Province, National Natural Science  Foundation of China, the startup funding from SUSTech, and the SMART  CAMP and Mechanobiology Institute of Singapore funding. 

    Paper link: https://www.sciencedirect.com/science/article/pii/S0142961220301010