# The contributions of inflammatory cocktail and stromal cell origin on a scaffold-free 3D biofabricated SSuPer tissue of endometriosis and normal endometrium

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $237,750

## Abstract

Endometriosis is a debilitating disease that affects up to 10% of U.S. women. While treatments exist, more than
50% of women with endometriosis will have disease recurrence. The lack of useful models continues to impede
the discovery of aspects of pathophysiology that are amenable to novel interventions. Therefore, there is an
urgent need to develop novel models of endometriosis to advance the field significantly. This application
proposes to create 3D biofabricated SSuPer (Self-Supporting Perfused) tissues that recapitulate either
endometriosis or normal endometrium using the Kenzan method. The Kenzan method uses the Regenova Bio
3D Printer to place multicellular spheroids onto a microneedle array, called a Kenzan. On Kenzan, the spheroids
fuse through cell-cell interaction and secretion of their native extracellular matrix, allowing more intrinsic
intercellular communication. Intercellular communication between epithelial and stromal cells is paramount in
endometrial function. Preliminary data shows that the Kenzan method effectively biofabricates the first
scaffold-free 3D bioprinted constructs comprised of both endometriotic epithelial and endometrial
stromal cells. Further, SSuPer tissues contain microchannels that can be perfused in a biologically inert
FABRICA bioreactor. Because human endometrial stromal fibroblasts are critical to uterine function, stromal
fibroblasts from women with endometriosis can be used to model the abnormal cellular function, aberrant
molecular signaling, and pro-inflammatory transcriptomic profiles that occur in endometriosis. Additionally, pro-
inflammatory mediators are elevated in the peritoneal fluid of women with endometriosis and likely play a role in
progesterone resistance. This application's objective is to biofabricate 3D models of both endometriosis and
normal endometrium, which recapitulate the inflammatory, transcriptomic, and steroid hormone response
faithfully. The central hypothesis is that both inflammatory cytokines and stromal cell origin (i.e., endometriosis
or not) independently affect the endometriotic or endometrial phenotype of each SSuPer tissue. SSuPer tissues,
comprised of epithelial and stromal cells from either endometriosis or normal endometrium, will be biofabricated
and perfused with either media or media with an inflammatory cocktail. SSuPer tissues will be determined to be
either endometriosis or normal endometrium by inflammatory marker secretion, expression of endometriosis
biomarkers, and global transcriptomic changes. Secondary validation studies will focus on steroid hormone
response. The research proposed in this application is innovative because it will generate novel scaffold-free 3D
biofabricated SSuPer tissues that maintain high biological fidelity to endometriosis or normal endometrium.
Rigorously validated in vitro models will provide useful models for investigating the pathophysiology of
endometriosis and other uterine dysfunction diseases such as infertility and rec...

## Key facts

- **NIH application ID:** 10218664
- **Project number:** 1R21HD102653-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Shannon Michelle Hawkins
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $237,750
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218664

## Citation

> US National Institutes of Health, RePORTER application 10218664, The contributions of inflammatory cocktail and stromal cell origin on a scaffold-free 3D biofabricated SSuPer tissue of endometriosis and normal endometrium (1R21HD102653-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10218664. Licensed CC0.

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