# F31 Mulero Russe

> **NIH NIH F31** · GEORGIA INSTITUTE OF TECHNOLOGY · 2022 · $46,752

## Abstract

PROJECT SUMMARY
Inflammatory Bowel Diseases (IBD) currently affect >1.6 million Americans. IBD is characterized by disruption
to the intestinal epithelium and a high inflammatory environment. Available treatments target the inflammation
through biological agents, however, fewer efforts have focused on epithelium healing and there are no broadly
applicable therapies to repair intestinal epithelium. Human intestinal organoids (HIOs) are three-dimensional (3D)
multicellular structures, derived from either adult intestinal stem cells or human pluripotent stem cells (hPSCs),
that recapitulate human intestinal tissue architecture. HIOs are a promising cell source for intestinal epithelium
repair, disease modeling, and drug screening. Previous work has demonstrated that HIOs engraft to the injured
intestinal wall in vivo, however, these approaches are significantly limited by the lack of an appropriate delivery
vehicle to drive HIO engraftment. HIO generation from hPSCs is multi-stage directed differentiation process
comprising three stages: (I) differentiation into a definitive endoderm monolayer, (II) hindgut and primitive tube
differentiation into free-floating, self-organized 3D aggregates (human intestinal spheroids, HIS), and (III)
intestinal specification into HIOs within a 3D extracellular matrix. This in vitro culture process spans a 2D growth
substrate (stage I and II) to a 3D matrix (stage III). Stage III requires culture within Matrigel, a murine tumor-
derived basement membrane extract with ill-defined composition, lot-to-lot variability, and limited clinical
translation potential. Another roadblock to HIO technologies is the low yield and consistency of HIS differentiation
in HIOs. The objectives of this project are to (1) engineer a synthetic hydrogel platform with independent control
of the biochemical and biophysical cues guiding the entire in vitro differentiation of hPSCs into HIOs, and (2)
deliver HIOs in a synthetic coating to intestinal injuries in vivo. The central hypothesis is that an engineered
synthetic matrix with appropriate biophysical and biochemical cues will support the HIO self-organization, growth,
and differentiation process and enhance HIO engraftment and healing of intestinal wounds. Aim 1: Engineer a
2D synthetic matrix promoting spheroid generation from hPSCs. Aim 2: Evaluate the maturation of HIOs from
the generated spheroids within synthetic niches. Aim 3: Engineer a clinically translatable therapeutic delivery
material for HIOs to injured intestinal tissue. The results of this study will increase the clinical relevance the
generated HIOs and will provide a scalable and translatable synthetic material for the differentiation and delivery
of HIOs.

## Key facts

- **NIH application ID:** 10463993
- **Project number:** 1F31DK130581-01A1
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Adriana Mulero-Russe
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463993

## Citation

> US National Institutes of Health, RePORTER application 10463993, F31 Mulero Russe (1F31DK130581-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10463993. Licensed CC0.

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