# Targeted cell delivery for treatment of non-healing wounds and gangrene

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $731,645

## Abstract

Abstract
Patients suffering from limb non-healing ulcers or gangrene caused by critical limb ischemia (CLI)
induced by peripheral arterial occlusive disease (PAD) or diabetes are at very high risk of major
amputation and experience poor physical function and severely diminished quality of life.
Particularly, CLI in diabetic patients is associated with high rates of morbidity and mortality. CLI
and diabetes-associated non-healing wound and gangrene result in over 130K major limb
amputations and over $2 billion health care costs in the USA every year. There is a formidable
need for novel therapeutic strategies. Our goal is to develop novel therapeutic strategies that will
accelerate neovascularization and tissue repair to eliminate the need for major amputation. Cell-
based therapy has emerged as a promising modality that can help to heal ulcers, increase
ischemic limb functional recovery, prevent major amputation, and improve quality of life and
survival in patients with CLI and diabetes. Bone marrow (BM)-derived tissue repair cells (TRC)
represent an alternative beneficial therapeutic option to induce therapeutic angiogenesis and
promote tissue regeneration. However, targeted systemic delivery of therapeutic cells to the
disease tissues, which has certain advantages to local administration approach, remains one
formidable challenge. We have recently developed a nanocarrier-mediated cell delivery method
by coating the surface of the cells to be delivered with dendrimer nanocarriers modified with
adhesion molecules. Nanocarriers can function as `GPS' to direct infused transplanting cells reach
to destination via recognition and association with the counterpart adhesion molecules highly or
selectively expressed on the activated endothelium in injured tissues. Once anchored on the
activated endothelium, nanocarriers-coated cells extravasate and home to the targeted tissues to
execute their therapeutic role. We thus propose to test and optimize this newly-developed
targeted cell delivery platform to direct TRC specifically and efficiently home to ischemic and
wound tissues to achieve therapeutic angiogenesis and tissue repair. Our proposal applies novel
cell surface decoration method for targeted cell delivery, new mouse gangrene and powerful pig
wound models to test feasibility and efficacy of novel nanocarrier-mediated targeted cell therapy
in promoting tissue neovascularization and tissue repair. The proposed study is translatable for
developing and optimizing safe and effective cell-based therapies for clinical trials. It may offer a
new paradigm for advancing and transforming the field of non-invasive treatment for PAD/CLI.

## Key facts

- **NIH application ID:** 10395481
- **Project number:** 5R01HL149452-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Sylvia Daunert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $731,645
- **Award type:** 5
- **Project period:** 2019-05-15 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395481

## Citation

> US National Institutes of Health, RePORTER application 10395481, Targeted cell delivery for treatment of non-healing wounds and gangrene (5R01HL149452-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10395481. Licensed CC0.

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