# Single cell characterization of the biomaterial immune and stromal response

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $618,965

## Abstract

Profiling single cells using single cell RNA sequencing (scRNAseq) is revolutionizing our understanding of
development and disease. In this proposal, we will apply scRNAseq to create an atlas of cells that respond to
biomaterials that induce divergent responses and serve as a model for tissue microenvironments of repair
versus fibrosis. The proposed research aims to leverage single cell analysis to define key subpopulations in
the lymphoid, myeloid and stromal fibroblasts response to biomaterial models of tissue fibrosis and repair.
Minimally processed biological scaffolds induce a Type 2 immune response characterized by interleukin (IL)-4
and tissue repair, similar to muscle repair processes. Our preliminary data describes a Type 17 immune and
senescent cell response to synthetic implants that induce fibrotic capsule formation in an IL-17-dependent
manner. We also demonstrate the ability of scRNASeq to uncover new macrophage cell populations in
biomaterial microenvironments. We hypothesize that by sorting cell subpopulations in the FBR in vivo,
combined with single cell analysis, we will identify new and rare populations that will help elucidate
mechanisms and provide new therapeutic targets to enhance tissue repair or reduce fibrosis. The following
specific aims are proposed to accomplish this goal:
Specific Aim 1. Identify and characterize lymphoid, myeloid, and fibroblast subpopulations isolated from
synthetic and biological scaffold implants using single cell RNA sequencing analysis.
Specific Aim 2. Computationally phenotype cell clusters both within and across cell types to define distinct
subsets and interaction models using pseudotime analysis, RNA velocity, differential expression and gene set
enrichment, cluster analysis to predict unique surface markers/combinations, and cell interactions analysis.
Specific Aim 3. Define unique surface and intracellular markers from single cell analysis to identify
subpopulations using standard experimental methods. Newly-identified immune and fibroblast subpopulations
will be evaluated over time in male and female mice and results will be validated with diverse materials.
The cell atlas created in the proposed research will enable future mechanistic studies and investigation into the
potential broad applicability to wound healing, cancer and other tissue pathologies.

## Key facts

- **NIH application ID:** 9864786
- **Project number:** 1R01EB028796-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** JENNIFER H ELISSEEFF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $618,965
- **Award type:** 1
- **Project period:** 2020-08-06 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864786

## Citation

> US National Institutes of Health, RePORTER application 9864786, Single cell characterization of the biomaterial immune and stromal response (1R01EB028796-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864786. Licensed CC0.

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