Bioprinted 3D Primary Human Intestinal Tissues Model Aspects of Native Physiology and ADME/Tox Functions

Area of Science:

• Biotechnology
• Drug Development
• Tissue Engineering

Background:

• The human intestinal mucosa is vital for drug absorption, distribution, metabolism, excretion (ADME)/Tox studies.
• Replicating the complex in vitro intestinal environment for drug development poses significant challenges.

Purpose of the Study:

• To engineer a 3D bioprinted intestinal tissue model that accurately recapitulates native human intestinal architecture and function.
• To evaluate the utility of this model in predicting drug ADME/Tox properties and enhancing preclinical safety assessments.

Main Methods:

• Utilized bioprinting technology to construct 3D intestinal tissues from human primary intestinal epithelial cells and myofibroblasts.
• Characterized the tissue's epithelial polarity, tight junctions, cell-type specialization, and expression of CYP450 enzymes.
• Assessed barrier function, transporter activity (P-gp, BCRP), and response to compound-induced toxicity and inflammation.

Main Results:

• The 3D intestinal tissues exhibited polarized epithelia with tight junctions and specialized cell types.
• Demonstrated functional and inducible CYP450 enzymes, physiological barrier function, and active drug transporters (P-gp, BCRP).
• The model successfully responded to compound-induced toxicity and inflammation, showing injury responses.

Conclusions:

• The bioprinted 3D intestinal tissue serves as a functional in vitro model of the human intestine.
• This model enhances the prediction of drug safety and efficacy, bridging the gap between preclinical studies and clinical trials.