# Spatial patterning modulates tissue revascularization and regeneration

> **NIH NIH R00** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $244,683

## Abstract

PROJECT SUMMARY
 8.5 million people in the United States suffer from peripheral arterial disease (PAD). As the disease
progresses, it can lead to severe obstruction of arterial blood flow to the extremities causing critical limb
ischemia, and is associated with devastatingly high mortality rates of up to 20% just 6 months from initial
diagnosis. This condition requires immediate endovascular treatment to re-establish blood flow, commonly
through the use of stents, balloon angioplasty, or autologous vein grafts; however, these treatments require
multiple interventions and do not conclusively lower the amputation rates. Therapeutic interventions aimed at
long-term functional recovery must augmenting tissue angiogenesis concomitant with restoring physiological
tissue architecture. This K99/R00 Pathway to Independence Award builds on previous work that demonstrates
that spatial patterning cues from nanoscale extracellular matrices modulate endothelial cell (EC) morphology
and angiogenic function. The objective of the current study is to use nanoscale cell guidance from aligned 3D
scaffolds to enhance the angiogenic potential of vascular ECs, with the regenerative goal of restoring blood
flow to ischemic regions and enabling functional repair of severely damaged tissue, an important public health
goal that has been challenging to attain.
 First, this award will provide the opportunity to examine the role of spatial patterning using aligned
versus non-patterned scaffolds, in the enhancement of EC angiogenic function as well as the modulation of
muscle myoblasts phenotype and mechanical properties. In parallel with this aim, the therapeutic efficacy of
EC-seeded aligned scaffolds in comparison to non-patterned scaffolds, will be assessed for tissue
revascularization and muscle regeneration in a mouse model of volumetric muscle and vascular injury.
Through these studies, the challenge of restoring both vascular and muscular function to injured tissues is
tackled on multiple fronts by using spatial cell patterning to induce an EC phenotype concomitant with
angiogenesis that will in turn enhance muscle myofiber differentiation and maturation. Finally, to gain a deeper
understanding of the mechanisms by which gene networks and pathways work in concert to promote
angiogenesis through spatial patterning, methodologies in gene silencing and functional genomics will be
employed to reveal novel cell patterning pathways. The proposed training will include courses offered through
the Stanford School of Medicine and externships with leading experts in the fields of cardiovascular medicine,
data science, and muscle regeneration. The proposed series of studies will deepen the understanding of the
biological mechanisms through which spatial cell patterning confers enhancement of EC angiogenesis and
muscle myoblast function. Findings from these studies will provide insights that will inform future regenerative
strategies and engineered therapeutics for revascularizatio...

## Key facts

- **NIH application ID:** 10368134
- **Project number:** 5R00HL136701-05
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Karina Nakayama
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $244,683
- **Award type:** 5
- **Project period:** 2020-03-20 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368134

## Citation

> US National Institutes of Health, RePORTER application 10368134, Spatial patterning modulates tissue revascularization and regeneration (5R00HL136701-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10368134. Licensed CC0.

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