# Studying astrocyte borders using injectable biomaterials

> **NIH NIH R21** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2024 · $446,126

## Abstract

Astrocyte border formation involving proliferative reactive changes in local astrocytes is a conserved feature of
many CNS disorders including neurotraumatic, neurodegenerative, neuroinflammatory, and neoplastic
diseases. Across disorders, astrocyte borders form against a non-neural niche compartment, containing
stromal and peripherally derived myeloid cells, whose cellular composition varies across disorders and stages
of disease. Despite targeted loss of function studies revealing the neuroprotective roles of astrocyte borders,
the context-specific functions of astrocyte borders at different non-neural niches are still poorly understood.
The development of new tools and techniques to dissect the complex biology at astrocyte borders in a
simplified, focal, and reproducible model system is needed to address important knowledge gaps. Injecting
biomaterials into mouse brain promotes spatiotemporally controlled astrocyte border formation and we see an
opportunity to use biomaterials to generate a new bioassay to study astrocyte borders. The main objective of
this project is to advance a new bioassay to stimulate and characterize astrocyte borders and use this
bioassay to profile several different functional states of astrocyte borders conferred by interactions with diverse
non-neural cell populations. Our overall hypothesis is that by locally injecting cellulose-based biomaterials with
different physiochemical properties into the mouse striatum we will stimulate distinct non-neural niches that will
confer temporal- and biomaterial-dependent changes in astrocyte states during the transition into astrocyte
borders which we can profile. In aim 1, we will optimize the bioassay to study astrocyte borders by combining
injectable, non-resorbable methyl cellulose hydrogels with viral vectors (AAVs) enabling astrocyte specific
expression of RiboTag. At 7, 14, 28, and 70 days after hydrogel injection into the mouse striatum, mRNA from
the formed astrocyte borders will be recovered by RiboTag immunoprecipitation and processed by RNA-Seq.
Cohorts of mice taken at the same timepoints will be processed by IHC to visualize changes in astrocyte
morphology, ribosome trafficking, and multicellular interactions. To validate capacity to detect altered astrocyte
border states we will disrupt astrocyte border formation by controlled release of molecular inhibitors. In aim 2,
we will evaluate astrocyte border states at non-neural niches with different immune cell compositions that will
be created by chemically modifying cellulose-based hydrogels to display non-fouling, immunosuppressive, or
immunostimulatory functional groups as well as through local delivery of small molecule immunoregulators
from hydrogels. Through this project, we will make important technical innovations to develop a new bioassay
that will allow us to identify conserved- and context-dependent mechanisms involved in astrocyte border
formation and function. This work will provide the foundations on whic...

## Key facts

- **NIH application ID:** 11057142
- **Project number:** 1R21NS136831-01A1
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Timothy Mark O'Shea
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $446,126
- **Award type:** 1
- **Project period:** 2024-09-20 → 2026-09-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11057142

## Citation

> US National Institutes of Health, RePORTER application 11057142, Studying astrocyte borders using injectable biomaterials (1R21NS136831-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/11057142. Licensed CC0.

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