# VEGF ligand presentation and therapeutic angiogenesis

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $7,245

## Abstract

Summary
Stroke is the leading cause of disability in the US, and, apart from physical therapy, therapeutic options to reduce
this burden are non-existent. Following a stroke, cell death and glial scarring leads to the formation of a non-
regenerative stroke cavity surrounded by the regenerative peri-infarct region. We are interested in understanding
how bioengineered therapeutics can synergize with pro-repair programs active in the peri-infarct region to
promote tissue regeneration in the stroke cavity and thereby improve neurological recovery. We have previously
engineered a dual-acting angiogenic hydrogel that, when injected into the stroke cavity, can reduce glial scarring
and promote vascularization to allow axonal infiltration. Although achieving brain repair in the stroke cavity is
remarkable, these results were achieved in young mice with un-impaired neuroplasticity. We believe that to bring this
technology closer to clinical translation, we must be able to show similar brain repair and behavioral improvement in more
clinically relevant animal models, like aged mice with decreased neuroplasticity. In this application, we aim to identify
our angiogenic hydrogel’s mechanism of action and optimize its formulation and to utilize this new formulation in
a stroke models with decreased neuroplasticity. The hydrogel is composed of hyaluronic acid functionalized with
cell-binding integrins and loaded with clustered vascular endothelial growth factor (VEGF) and heparin
nanoparticles. Heparin is a known anti-inflammatory agent that potentially acts by breaking the inflammatory
cycle between macrophages and astrocytes following stroke. We will use design of experiment methodology to
determine the composition of these three factors (integrins, clustered VEGF, and heparin nanoparticles) that
leads to substantial brain repair (Aim 1) and assess how the hydrogel components modulate the pro-repair
environment by analyzing temporal changes in proteins, mRNA, and immune cell populations following stroke
(Aim 2). Using the improved formulation, we will also evaluate the angiogenic hydrogel’s ability to promote
neurological regeneration and functional recovery in more rigorous animal models, specifically aged mice treated
immediately following cerebral ischemia and young mice with cerebral ischemia treated as the plasticity window
is closing (Aim 3). Overall, we aim to deepen our understanding of how bioengineered therapeutics synergize
with endogenous pro-regenerative programs and thereby improve behavioral outcomes following stoke in more
difficult-to-treat cases.

## Key facts

- **NIH application ID:** 10455833
- **Project number:** 3R01NS079691-08S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Tatiana Segura
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $7,245
- **Award type:** 3
- **Project period:** 2012-05-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455833

## Citation

> US National Institutes of Health, RePORTER application 10455833, VEGF ligand presentation and therapeutic angiogenesis (3R01NS079691-08S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10455833. Licensed CC0.

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