# An Engineered Tissue Model of Aged Mammary Microenvironment

> **NIH NIH R01** · UNIVERSITY OF NOTRE DAME · 2021 · $382,965

## Abstract

Project Summary
Aging of breast tissue microenvironment has reported to form a fertile soil facilitating tumor progression. As
tissue hemostasis evolves over the course of aging, developing models that enable the exploration of tumor
progression in aging niche is important for understanding the disease, identifying crucial pathways, and finding
control points that could be amenable to therapeutic intervention. Systematic inquiry of the aged breast tissue
environment has been challenging and cost prohibitive, due to 1) lack of aged NORMAL breast tissue (an ideal
control) for tissue microenvironment analysis and 2) the logistic barrier of lengthy aging process when using
experimental mouse models. A fully characterized, tissue engineered breast model that faithfully recapitulates
breast cancer development in an aging-mimicking tissue would be a novel platform for studying breast cancer
progression, and would bring a new perspective to breast cancer research. Using a microfabricated tissue
engineered model, we can explore what constitutes a permissive aging stromal environment by modulating
variables such as matrix stiffness, matrix components, stromal cell density and organization, etc. The central
goals of the proposed effort are to establish an Aging-mimicking Breast Tissue engineered (ABTe) that will be used
to characterize the factors that contribute to the permissive environment in aging tissues, including the physical,
chemical, and cellular cues, and to investigate whether therapeutic modulation can affect tumor progression in
aging microenvironment. Specifically we aim to 1) Characterize biophysical properties and biochemical
composition of extracellular matrices (ECM) of aged breast tissue; and 2) Build ABTe system and model ECM
heterogeneity by tuning aging-related ECM factors including ECM stiffness, ECM composition, and stromal
adipocytes spatial distribution, and then 3) test the clinical relevance and power of the developed ABTe by running
chemoprevention trails for prevention of transition from Ductal Carcinoma In Situ (DCIS) to Invasive Ductal
Carcinoma (IDC). To achieve these goals, we will combine our expertise of tissue engineering and breast cancer
research. Once fully implemented and functionally validated, we expect our state-of-the-art tissue engineered
ABTe cancer model to serve as the next-generation research platform for both basic and translational cancer
research and high-throughput drug discovery. The tissue engineered ABTe will greatly facilitate research efforts
in important, while traditionally less accessible, areas of cancer research and beyond.

## Key facts

- **NIH application ID:** 10090595
- **Project number:** 5R01EB027660-03
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Pinar Zorlutuna
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,965
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10090595

## Citation

> US National Institutes of Health, RePORTER application 10090595, An Engineered Tissue Model of Aged Mammary Microenvironment (5R01EB027660-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10090595. Licensed CC0.

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