# Paper-based cultures supporting tissue-like structures for biochemical studies of oxygen gradients and screening applications

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $77,425

## Abstract

Abstract
Despite the importance of extracellular gradients in the formation and maintenance of tissue formation, there
are few analytical tools capable of generating tissue-like environments with experimentally defined and
physiologically relevant oxygen gradients. Current 3D culture tools have not been widely adopted because
they require specialized equipment and engineering expertise to set up, maintain, and analyze. These devices
often do not interface well with current cell-based analyses such well plate end-point analyses or the selective
removal and lysis of cells for molecular biology readouts (e.g., qPCR, Western blots, immunoassays). To
enable the study of oxygen's role in directing responses at the cellular, tissue, and organ level, culture
platforms that are readily accessible to laboratories who specialize in cell and molecular biology are needed.
This MIRA proposal continues to innovate paper-based scaffolds as support for preparing tissue-like
structures. This platform is unlike any other, employing readily available materials and simple technological
solutions, to generate 3D cultures with defined extracellular environments, regardless of cell type or tissue
structure. The level of experimental control afforded by the paper-based culture platform makes it a powerful
enabling technology to probe cell-environment relationships in a spatially resolved manner. Using diffusion-
dominated gradients, similar to those that form in healthy and poorly vascularized tissues, we are: 1)
Developing tools to characterize the gradients that form in real-time, focusing on oxygen, pH, glucose, and
lactate. 2) Evaluating differences between immotile and highly invasive cells, to determine the
microenvironment's role—in particular, oxygen gradients—in promoting movement and drug resistance. 3)
Generating tissue-like co-cultures with physiologically relevant oxygen gradients, with a specific focus on
oxygen's role in liver zonation and hormone regulation in a breast lumen model. 4) Developing a platform to
screen multiple 3D tissue structures in parallel. The ability to generate and evaluate many tissue structures
in parallel will significantly improve screening processes to assess liver toxicity and identify potential endocrine
disruptors.

## Key facts

- **NIH application ID:** 10133780
- **Project number:** 3R35GM128697-02S2
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Matthew Ryen Lockett
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $77,425
- **Award type:** 3
- **Project period:** 2018-07-05 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133780

## Citation

> US National Institutes of Health, RePORTER application 10133780, Paper-based cultures supporting tissue-like structures for biochemical studies of oxygen gradients and screening applications (3R35GM128697-02S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133780. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*