# Angiogenic growth factor delivery for vascular regeneration in critical limb ischemia using acoustically-responsive scaffolds

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $715,226

## Abstract

ABSTRACT
The development of techniques to generate functional, perfused blood vessel networks is essential for
engineering of viable tissues as well as for the treatment of ischemic diseases. Pro-angiogenic growth factors
have been used, either as a standalone therapy or in combination with cell-based techniques, to promote
vascularization. Unfortunately, conventional approaches for delivery of pro-angiogenic growth factors have
yielded disappointing results in clinical, therapeutic trials. This is because optimal growth factor combinations,
concentrations, release kinetics, and spatial presentations are unknown. Thus, there is a need to develop
translatable technologies for precisely controlling these parameters so optimization can be achieved. Our long-
term goal is to develop implantable biomaterials for tissue regeneration that are spatiotemporally manipulated
in a non-invasive, on-demand manner using focused ultrasound. Focused ultrasound is a clinically-used
technology with sub-millimeter precision that penetrates deeply within the body. During the prior funding
period, we developed a paradigm-changing hydrogel, termed an acoustically-responsive scaffold (ARS) that
enables the controlled release of multiple, pro-angiogenic growth factors using ultrasound. An ARS consists of
an ultrasound-sensitive emulsion embedded within a hydrogel matrix. Growth factors encapsulated within the
emulsion are released when an ARS is exposed to focused ultrasound. This non-thermal release mechanism,
termed acoustic droplet vaporization (ADV), is driven by the formation of a bubble within each emulsion
droplet, thereby releasing the encapsulated payload. We developed techniques to sequentially release basic
fibroblast growth factor (bFGF) and platelet derived growth factor-BB (PDGF-BB) from an ARS. We also
demonstrated that ADV can release bioactive bFGF with high specificity, thereby leading to the formation of
functional vessels in vivo. The kinetics of bFGF release strikingly impacted the formation of perfused blood
vessels. ADV-generated bubbles also dramatically altered the permissiveness of the ARS to cell migration.
The objective of this proposal is to understand how vascularization is impacted by spatiotemporal variation of
release kinetics of bFGF and PDGF-BB from an ARS as well as permissiveness of the ARS. The central
hypothesis is that optimal blood vessel formation can be achieved by precisely controlling growth factor release
from ARSs using ADV-generated bubble dynamics. Aim 1 will use ADV-generated bubble dynamics to
modulate the kinetics of growth factor release from an ARS. Aim 2 will quantify the impact of bFGF release
kinetics and ARS permissiveness on the development and inosculation of cell-loaded ARSs. Aim 3 will
demonstrate enhanced vascularization in an atherosclerotic model of hind limb ischemia by sequentially
delivering bFGF and PDGF-BB from acellular ARSs. Successful completion of these aims will advance the
translation of pro-angi...

## Key facts

- **NIH application ID:** 10764787
- **Project number:** 5R01HL139656-07
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Mario Leonardo Fabiilli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $715,226
- **Award type:** 5
- **Project period:** 2017-12-15 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764787

## Citation

> US National Institutes of Health, RePORTER application 10764787, Angiogenic growth factor delivery for vascular regeneration in critical limb ischemia using acoustically-responsive scaffolds (5R01HL139656-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10764787. Licensed CC0.

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