# Biomaterials to promote synapse formation after stroke

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $65,769

## Abstract

Summary
Stroke is the leading cause of adult disability in the US. There are no therapeutic options beyond physical therapy
to reduce disability burden; thus, new therapeutic options are highly needed. The stroke cavity is the region of
the brain that dies after stroke and does not spontaneously regenerate. We are interested in designing injectable
hydrogel formulations that can promote brain tissue repair after stroke and propose that intra core injection can
be an ideal delivery location. We engineered an angiogenic hydrogel that re-vascularizes the necrotic stroke
cavity, promotes vascular and neurological tissue formation within the stroke core, and promotes behavioral
improvement. Achieving any type of brain repair in the stroke cavity is remarkable. We cannot be sure if
behavioral improvement occurred because of this new tissue formation or due to improved peri-infarct plasticity.
Nevertheless, behavioral improvement was observed between 12 and 16-weeks. We believe that to bring this
technology closer to clinical utility, we must be able to improve the recovery timeline to closer to 4 weeks post
stroke. In this proposal, we will investigate synapse formation and improved mechanical support as a way to
improve recovery timeline after cortical ischemic stroke. Astrocytes play a critical role in synapse formation and
pruning; thus, we will investigate several approaches to modulate this cell population in the brain post stroke and
also the delivery of secreted astrocyte proteins that are known to play a role in synapse formation. This proposal
builds upon our preliminary data that porous scaffolds promote astrocyte infiltration into the material post stroke,
that integrin binding can dictate differentiation of neuroprogenitor cells into astrocytes, and that TSP-1 can
promote similar levels of synapse formation as astrocytes. In particular, we will study how scaffold microstructure
and incorporation of bioactive signaling molecules can promote astrocytic infiltration or differentiation of
progenitor cells towards an astrocytic lineage (Aim 1), how the incorporation of our current angiogenic strategy
into a porous scaffold impacts behavioral improvement (Aim 2), how the delivery of TSP-1 from our porous
scaffolds influences brain repair and behavioral improvement post stroke. Overall, we aim to engineer a pro-
synaptic material that could improve on the timeline and degree of behavioral improvement after stroke.

## Key facts

- **NIH application ID:** 10453306
- **Project number:** 3R01NS112940-02S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Tatiana Segura
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,769
- **Award type:** 3
- **Project period:** 2020-03-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453306

## Citation

> US National Institutes of Health, RePORTER application 10453306, Biomaterials to promote synapse formation after stroke (3R01NS112940-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10453306. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*