# Regulation of Angiogenic Neovessel Invasion Across Tissues

> **NIH NIH F31** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $33,865

## Abstract

Project Summary / Abstract
Angiogenesis – the growth of new blood vessels from an existing vasculature – is an essential process that takes
place in disease such as tumor metastasis, ordinary physiological functions such as wound healing, and tissue
engineering research for efficient transport of nutrients. The technological needs of modern medicine require
manipulation of the microvasculature to inhibit or promote angiogenesis, but we cannot achieve this goal yet as
our understanding of angiogenesis does not explain vascular guidance across tissue compartments. Although
significant advances have been made in the characterization of molecules, pathways, and reactions, the process
by which growing neovessels navigate complex tissue structures is poorly understood. Our driving hypothesis is
that biophysical signals originating from neovessel interaction with the surrounding matrix, are sufficient to deter
directed neovessel growth. Additionally, we also hypothesize that the integration of biophysical signals along
with biochemical cues lead to unique vessel behavior, and this integration process is highly nonlinear. To address
the problem of angiogenic guidance across tissue structure, a collagen-based organ culture of angiogenesis is
used to mimic extracellular boundaries, coupled with an imaging pipeline to record time-dependent phenomena,
and a computational model for further testing of proposed mechanisms. In Aim 1, we will examine extracellular
matrix structural characteristics that modulate neovessel growth across a boundary. Quantitative 4D microscopy
will be used to measure collagen fiber orientations and density simultaneously with neovessel growth past the
boundary. Computational modelling based on proposed mechanisms of guidance will be conducted and
compared with experimental results to further test our hypothesis. In Aim 2, macrophages will be added to the
cultures at different positions to study their modulation of angiogenesis in conjunction with biophysical
mechanisms from Aim 1. The addition of these cells advances our culture system closer to in vivo angiogenesis,
and helps elucidate further mechanisms of angiogenic control. Quantitative 4D microscopy will be used to
measure extracellular structural parameters, neovessel growth, and macrophage position and migration. The
proposed mechanisms of neovessel migration will be further tested using computational modelling to determine
the effect of macrophages vascular invasion within our mechanistic understanding. Together, these studies will
characterize the relationship between growing blood vessels and their surrounding environment along with
modulation by stromal macrophages. This research will provide new insight to angiogenic mechanisms driving
guided neovessel growth and provide new research avenues to further understand angiogenesis.
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## Key facts

- **NIH application ID:** 10271256
- **Project number:** 5F31HL154781-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** ADAM RAUFF
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,865
- **Award type:** 5
- **Project period:** 2020-08-10 → 2022-08-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271256

## Citation

> US National Institutes of Health, RePORTER application 10271256, Regulation of Angiogenic Neovessel Invasion Across Tissues (5F31HL154781-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10271256. Licensed CC0.

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