# 3D Renal Tissue Chip Models to Evaluate Nephrotoxic Effects of Drugs

> **NIH NIH F31** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $37,326

## Abstract

PROJECT SUMMARY
The current pathway for drug discovery is associated with costs of $2.55 billion and between 10-15 years of
development for a single drug to reach the market. The challenges in predicting drug toxicities and efficacies are
attributed to inherent species differences in drug-metabolizing enzyme activities and cell-type-specific
sensitivities to toxicants. Organs-on-a-chip are an emerging technology in disease modeling and screening
therapeutics to address discrepancies between animal models and human clinical trials. They utilize tissue
engineering, fluid mechanics, and biomaterials to replicate in vivo architectures and functions of complex organs
and tissues. The renal proximal tubule (PT) in vivo is exposed to fluid flow and mechanical stress (pressure,
stretch, shear) and these stimuli play an important role in maintaining cellular phenotype and homeostasis.
Currently, available prototypes fall short of replicating the in vivo environment because they often fail to mimic
the physiological forces. Therefore, these models have had limited success in predicting drug-induced
nephrotoxicity. In this proposal, we will bioengineer and evaluate a dynamic platform of the PT and study the
effects of drugs and tubular dysfunction to establish its potential for translational research. Human renal proximal
tubule cells (hRPTECs) will be cultured within gelatin methacryloyl (GelMA) hydrogels under physiological shear
and pressure. These devices will also incorporate the diversity in the patient population by using hRPTECs from
multiple donors to determine the impact of age, sex, and racial differences on nephrotoxicity effects. Drugs will
be classified based on their nephrotoxic risk (high, intermediate, and low) and the platform will incorporate
automated readouts to reflect cellular function and viability. Together, this will help investigate more accurate
pharmacological and pathological responses and to determine the utility of in vitro perfusion models. Secondly,
a more complex and novel bioengineered platform will be developed. This design contains a 3D PT tubule and
3D vascular vessels surrounded by pericyte vascular networks. The platform will then be subjected to
physiological shear stress and pressure to demonstrate the flow loop can accurately mimic cellular organization,
establishment of tight junctions, maintenance of barrier function, and selective transport as seen in vivo. This
device composes of a co-culture of hRPTECs, human umbilical vein endothelial cells (hUVECs), and human
dermal fibroblasts (hDF) within a GelMA hydrogel to model an environment where both reabsorption and
secretion functions are replicated. Lastly, this proposal investigates the translational potential of PT tissue chips
through demonstration of a PT diabetic nephropathy model and engineering multi-well PTs to facilitate high-
throughput studies. The organ-on-a-chip developed in this study will provide an enabling technology that has
broad applications i...

## Key facts

- **NIH application ID:** 10249974
- **Project number:** 5F31DK127809-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Leslie Donoghue Seeley
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $37,326
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249974

## Citation

> US National Institutes of Health, RePORTER application 10249974, 3D Renal Tissue Chip Models to Evaluate Nephrotoxic Effects of Drugs (5F31DK127809-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10249974. Licensed CC0.

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