3D Printed Stackable Titer Plate Inserts Supporting Three Interconnected Tissue Models for Drug Transport Studies.

Area of Science:

• Biomedical Engineering
• Pharmacology
• Tissue Engineering

Background:

• Current in vitro drug screening models using single cells lack precision in predicting drug absorption, distribution, metabolism, excretion, and toxicity (ADMET).
• Existing methods often fail to replicate the complex cellular interactions and physiological barriers crucial for accurate drug assessment.

Purpose of the Study:

• To develop and validate a novel 3D printed insert system for creating multi-tissue models in standard microtiter plates.
• To improve the predictability of in vitro drug screening by incorporating multiple cell types and simulating first-pass metabolism.

Main Methods:

• Fabrication of 3D printed inserts compatible with microtiter plates.
• Culturing of Caco-2, HUVEC, and HepG2 cells within gelatin hydrogels to create distinct tissue models (small intestine, vascular endothelium, liver).
• Stacking of differentiated cell cultures to form a multi-tissue model for simulating first-pass metabolism.

Main Results:

• Successful fabrication of user-friendly, 3D printed inserts for tiered cell culture.
• Demonstration of a functional multi-tissue model simulating first-pass metabolism using gelatin hydrogels and specific cell lines.
• The system provides a viable alternative to microfluidic organ-on-a-chip devices for ADMET studies.

Conclusions:

• The 3D printed insert system offers a simple, cost-effective, and scalable platform for advanced in vitro drug screening.
• This approach enhances the predictive power of drug ADMET studies by integrating multiple tissue models in a microtiter plate format.
• The developed system facilitates comprehensive drug absorption, distribution, metabolism, and excretion (ADME) analysis within a single, compact device.