Development of a biomimetic liver tumor-on-a-chip model based on decellularized liver matrix for toxicity testing

Area of Science:

• Biomedical Engineering
• Cancer Research
• Drug Development

Background:

• Cancer remains a significant global health threat, necessitating improved anti-cancer drug development.
• Current tumor-on-a-chip technologies have limitations in accurately mimicking the native tumor microenvironment (TME).

Purpose of the Study:

• To develop a biomimetic three-dimensional (3D) liver tumor-on-a-chip that better replicates the in vivo TME.
• To enhance the capability of tumor-on-a-chip models for drug toxicity screening and pharmacological studies.

Main Methods:

• Integration of decellularized liver matrix (DLM) components with gelatin methacryloyl (GelMA) within a microfluidics-based 3D dynamic cell culture system.
• Utilizing the DLM-GelMA composite to create a biomimetic liver tumor-on-a-chip model.
• Assessing cell viability, hepatocyte function, and drug dose-dependent responses under flow conditions.

Main Results:

• The DLM-GelMA liver tumor-on-a-chip demonstrated superior cell viability and enhanced hepatocyte functions compared to GelMA-only models under flow.
• The improved performance is attributed to the reestablishment of biochemical and biophysical cues, including growth factors, scaffold proteins, stiffness, and shear stress.
• The model exhibited linear dose-dependent responses to acetaminophen and sorafenib toxicity.

Conclusions:

• The DLM-GelMA biomimetic liver tumor-on-a-chip effectively recapitulates the 3D liver TME.
• This advanced model shows significant promise for improving pathological and pharmacological studies, particularly in anti-cancer drug development and toxicity assessment.