# Human 3D Microtissues for Toxicity Testing via Integrated Imaging, Molecular and Functional Analyses

> **NIH NIH U01** · BROWN UNIVERSITY · 2021 · $720,436

## Abstract

PROJECT SUMMARY
 Historically, toxicity testing has relied on high dose exposures in animals with default methods for
extrapolating to low level exposures in human populations, producing (at high cost) great uncertainty for
human health risk assessments. This Brown University Bioengineering Research Partnership (BRP)—Human
3D Microtissues for Toxicity Testing via Integrated Imaging, Molecular and Functional Analyses—
implements a transformative change by developing novel 3D human microtissues as a bridging technology
based on integrating imaging, molecular and functional analyses that will facilitate more rapid, cost-effective
toxicity testing of environmental chemicals and emerging toxicants.
 The project has two phases. Phase 1 establishes 3D microtissues of five tissue types (prostate, ovary,
lung, brain, heart) to address the key challenges facing development of these predictive biology platforms:
reproducibility, biological complexity, integrated endpoints, and human variability. Phase 2 selects two of these
3D microtissue models for computational systems biology analysis with sufficient dose- and time-response
data to define adverse points of departure for an in vitro-to-in vivo extrapolation and safety assessment.
 Working with collaborators and commercial partners, the BRP team includes faculty from biology,
engineering, mathematics, and medicine who have formed the Center to Advance Predictive Biology
(https://www.brown.edu/research/projects/center-to-advance-predictive-biology/). The following working
hypothesis guides the project: In vitro pathology assessment of human 3D microtissues within a
computational systems biology framework identifies toxicant-induced adverse points of departure for safety
assessment. The high content, high throughput platforms for these evaluations are 3D microtissue test
systems that re-capitulate the differentiated features and characteristic cellular functions of humans tissues.
Progress toward the goal of transforming toxicity testing will be made by addressing these Specific Aims:
  Specific Aim 1. Innovate the 3D microtissue platform with engineering solutions for improved well
 designs, confocal imaging, and high-throughput workflows
  Specific Aim 2. Optimize 3D microtissues as predictive biology platforms
  Specific Aim 3. Streamline image acquisition, reconstruction, and quantitative analysis for the in vitro
 pathology assessment of 3D microtissues
  Specific Aim 4. Integrate imaging, molecular, and functional endpoints within a computational systems
 biology framework for the purpose of human safety assessment
 This Brown University BRP will accelerate development and commercialization of human 3D
microtissue platforms as alternatives to animal toxicity testing.

## Key facts

- **NIH application ID:** 10240515
- **Project number:** 5U01ES028184-05
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** KIM BOEKELHEIDE
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $720,436
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240515

## Citation

> US National Institutes of Health, RePORTER application 10240515, Human 3D Microtissues for Toxicity Testing via Integrated Imaging, Molecular and Functional Analyses (5U01ES028184-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10240515. Licensed CC0.

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