# Delivery of apoptotic neutrophils to improve angiogenesis during wound healing

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $172,700

## Abstract

PROJECT SUMMARY/ABSTRACT
Every year, millions of patients suffer from impaired wound healing due to injuries, surgeries, and 
diseases, creating a significant public health and economic burden. The process of skin wound 
healing involves clotting, inflammation, cell proliferation and migration, re-vascularization, and 
remodeling, and often results in scarring. In diabetic patients or large wounds, insufficient 
angiogenesis slows healing and worsens scarring. Attempts to deliver growth and angiogenic 
factors or cells fall short of providing complete relief, and there is a critical need for new strategies 
to promote angiogenesis and tissue repair during wound healing. The proposed project aims to 
develop a novel therapeutic approach for improved angiogenesis during wound healing by 
leveraging natural interactions of immune cells. We propose to deliver apoptotic neutrophils (AN) 
within a degradable hydrogel scaffold that will induce efferocytosis and phagocytosis, respectively, 
in local macrophages (Mφs), promoting their angiogenic signaling and tissue repair without 
causing inflammation. In preliminary work, AN delivery in a gelatin methacrylate (GelMA)-based 
hydrogel significantly enhanced angiogenesis in a murine skin wound model, both in wild type 
and in diabetic mice. Furthermore, addition of AN and/or GelMA to macrophages in culture 
stimulated their secretion of angiogenic growth factors. We propose here to investigate the effects 
of GelMA-AN on Mφ uptake and growth factor secretion (Aim 1), and on angiogenesis and wound 
healing of a full-thickness skin wound (Aim 2). This project will establish a new method to enhance 
Mφ angiogenesis signaling, providing a platform for further investigation, and developing a 
therapeutic intervention for improved wound healing. This proposed approach leverages the role 
of immune cells and angiogenesis in wound healing, with modulation of Mφs phenotype 
conversion for successful wound healing and tissue repair.

## Key facts

- **NIH application ID:** 10989559
- **Project number:** 1R21AR083769-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Wendy Liu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $172,700
- **Award type:** 1
- **Project period:** 2024-08-20 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10989559

## Citation

> US National Institutes of Health, RePORTER application 10989559, Delivery of apoptotic neutrophils to improve angiogenesis during wound healing (1R21AR083769-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10989559. Licensed CC0.

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