# Biomaterial technologies for interrogating sex differences in tissue repair and homeostasis

> **NIH NIH R35** · UNIVERSITY OF KANSAS LAWRENCE · 2021 · $370,780

## Abstract

PROJECT SUMMARY
An individuals’ biological sex significantly affects their ability to repair and regenerate tissue. A clear example of
this is the reduced ability for women to heal and regenerate new, healthy tissue after menopause, which results
from a significant loss of sex hormone signaling. This reduction in hormone levels disproportionately enhances
the risk for many degenerative diseases including osteoporosis, osteoarthritis, cardiovascular disease, and
degenerative brain diseases in which the rate of tissue breakdown exceeds the rate of tissue repair. While it is
known that several factors contribute to sex differences in tissue repair including biomechanics, nutrition,
physical activity level and sex hormones, the interplay between these parameters is not well understood.
Specifically, it is unknown how the native sex differences in tissue structure and the resulting differences in
mechanical function dictate cell phenotype and behavior and how this effect interacts with estrogen signaling to
overall control tissue repair. Thus, a fundamental, mechanistic understanding of how a cell responds to the
spatial and mechanical cues of its environment while mediating estrogen signaling is critical to understand why
sex differences occur in tissue repair and homeostasis and for future patient-centered repair and regeneration
strategies. The overall goal of our research program aims to develop biomaterial tools to interrogate sex
differences in tissue repair and homeostasis. Theme 1: Do male and female MSCs respond to spatial and
mechanical properties of the cell microenvironment differently? There is evidence in many tissues that
extracellular matrix structure, organization, and resulting function differs between age-matched males and
females. However, there are no studies showing how this affects cell response. Biomaterials engineered to mimic
both the fibrous properties of structural collagens and the viscoelastic properties of proteoglycans in the native
extracellular matrix will be used to assess sex differences in cell response to controlled changes in matrix
properties. Theme 2: How does estrogen presentation to the cell affect downstream transcription and behavior?
While estrogen is known to play a role on cell processes, these results are dependent on the concentration and
the temporal presentation of estrogen to the cell. To address this limitation, we will use concentration gradient
generator microchips to quickly and accurately determine the effect of estrogen concentration and timing on cell
transcriptional activity. Theme 3: Can we engineer biomaterial systems to control release and presentation of
estrogen to the cells? Release rates in a range of hours to months will be controlled by modulating diffusion out
of the biomaterials via material chemistry and architecture. The ability to control the rate of release and localize
to a specific tissue in the body is critical to promote the estrogen effects at the site while reducing the ...

## Key facts

- **NIH application ID:** 10277013
- **Project number:** 1R35GM143081-01
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Jennifer Lindsey Robinson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $370,780
- **Award type:** 1
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10277013

## Citation

> US National Institutes of Health, RePORTER application 10277013, Biomaterial technologies for interrogating sex differences in tissue repair and homeostasis (1R35GM143081-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10277013. Licensed CC0.

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