# Angiogenic Bioengineered Systems to Optimize Post-Infarction Myocardial Recovery

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $620,196

## Abstract

PROJECT SUMMARY
Ischemic heart disease affects over 150 million people worldwide and remains a leading cause of death for
mankind. While overall mortality after myocardial infarction has improved, many patients ultimately succumb to
heart failure despite pharmacologic, revascularization, and reconstructive therapies due to microvascular
perfusion deficits which remain unaddressed. Targeted therapies such as cytokine, stem cell, and tissue-
engineering approaches to myocardial revascularization, repair, and regeneration have had varied success,
likely due to limitations in mechanistic understanding and suboptimal delivery systems. Thus, novel approaches
to microrevascularization are greatly needed. In the recent funding period, we further elucidated the native
signaling mechanisms of the angiogenic cytokine stromal cell-derived factor 1 (SDF) with its target, endothelial
progenitor stem cells, to better harness its therapeutic effect during post-infarction myocardial repair.
Furthermore, we synthesized a supra-efficient engineered SDF analog (ESA) and delivered it via a novel
biomaterial for prolonged therapeutic effect. These strategies revealed robust angiogenesis, improved
cardiomyocyte survival, preserved myocardial tissue biomechanics, reduced adverse post-injury remodeling,
and enhanced cardiac functional recovery. We also designed and constructed a tissue-engineered bilayer cell
sheet and demonstrated its ability to improve angiogenesis and ventricular remodeling. Finally, we have
translated elements of our work into pre-clinical large animal models to evaluate the potential of these therapies
to reach human clinical trials.
This renewal application proposes to further define the mechanisms underlying the therapeutic effects of SDF,
and to optimize cytokine delivery platforms for large animal and eventual human clinical translation. Aim 1 seeks
to delineate SDF/ESA molecular structure to guide synthesis of novel analogs with enhanced efficacy, genetically
manipulate SDF signaling to identify therapeutic targeting opportunities, and study the effects of
microrevascularization on cellular perfusion, tissue biomechanics, and ventricular function. Aim 2 proposes the
development of two innovative bioengineered cytokine delivery platforms for treating myocardial ischemia. One
encompasses a novel shear-thinning hydrogel with dual cytokine release modalities and the capacity for
percutaneous transcatheter delivery. Another involves fabricating a tissue-engineered SDF-eluting vascular
conduit to enable simultaneous macro- and microrevascularization. Aim 3 strives to scale these innovative
strategies to large animal pre-clinical models of percutaneous transcatheter therapeutics and minimally invasive
coronary artery bypass grafting with synthesized bioconduits. The proposed experiments will yield important
knowledge on potential clinical therapies for coronary artery disease, myocardial infarction, and heart failure.

## Key facts

- **NIH application ID:** 9887268
- **Project number:** 2R01HL089315-12A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Y Joseph Woo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $620,196
- **Award type:** 2
- **Project period:** 2008-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9887268

## Citation

> US National Institutes of Health, RePORTER application 9887268, Angiogenic Bioengineered Systems to Optimize Post-Infarction Myocardial Recovery (2R01HL089315-12A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9887268. Licensed CC0.

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