# Biofabrication of Multicompartment Human Liver Tissues for Chemical Screening

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $194,533

## Abstract

ABSTRACT / PROJECT SUMMARY
Title: Biofabrication of Multicompartment Human Liver Tissues for Chemical Screening
Drug-induced liver injury (DILI) is a leading cause of preclinical and clinical drug attrition, black box warnings on
drugs, and withdrawals of drugs from the marketplace. Unfortunately, animal models do not always suffice to
evaluate human DILI due to significant species-specific differences in drug metabolism pathways; therefore, in
vitro models of the human liver are being increasingly utilized to evaluate compound (drugs/chemicals)
metabolism and toxicity. However, current in vitro models of the human liver are unable to determine the effects
of compounds on the three major compartments of the liver, namely hepatic, vascular, and biliary, and how
toxicity to one compartment may affect the other compartments. Similarly, while there has been some progress
in developing implantable liver tissue surrogates as cell-based therapies for patients suffering from end-stage
liver failure, such tissues do not contain the above-mentioned liver compartments with physiological
interconnections. Our studies have shown that primary human hepatocytes (PHH) and liver endothelial cells
(LEC) display high levels of in vivo-like functions for 4+ weeks in vitro when organized into 3-dimensional (3D)
extracellular matrix (ECM) microgels that are generated using a high-throughput droplet microfluidics platform
(so-called microtissues). This microtissue technology is uniquely suited to control the microenvironment of liver
cells and could potentially protect cells from the shear stress induced via 3D bioprinting. Furthermore, we have
shown that cholangiocytes display sprouting behavior in decellularized liver ECM (dECM) but not in collagen-I
or Matrigel alone and such sprouting behavior can be directed via 3D bioprinting. In this high-risk/high-reward
R21 proposal, we will leverage these platforms and findings to test the novel hypothesis that a 3D-printed
biomaterial scaffold containing hepatic microtissues and liver dECM can be used to generate liver-like functional
and integrated compartments (vascular, hepatic, and biliary). In aim 1, we will fabricate and characterize 3D-
printed structures containing hepatic microtissues and LEC-lined vascular channels, while in aim 2, we will
incorporate cholangiocytes into the biofabricated structures and investigate the ability to control and detect bile
flow. If successful, our efforts will yield a first-of-its-kind scalable 3D-printed human liver tissue containing
integrated hepatic, vascular, and biliary compartments that displays stable levels of diverse liver functions for
several weeks in vitro. Ultimately, our 3D-printed human liver tissue can be used for investigating the effects of
compounds on all three compartments of the liver and their interactions, as well as for implanting into animal
models as potential cell-based therapy for chronic liver disease and acute liver failure.

## Key facts

- **NIH application ID:** 10457485
- **Project number:** 5R21ES033528-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Salman R Khetani
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,533
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457485

## Citation

> US National Institutes of Health, RePORTER application 10457485, Biofabrication of Multicompartment Human Liver Tissues for Chemical Screening (5R21ES033528-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10457485. Licensed CC0.

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