# Dual-Delivery of Bioactive and Anti-Microbial Nanowires for Accelerated Bone Repair

> **NIH NIH R01** · STEADMAN PHILIPPON RESEARCH INSTITUTE · 2022 · $43,428

## Abstract

ABSTRACT
Fractures are one of the most common injuries worldwide with an estimated 15 million fractures each year in the
United States alone. Complications in bone healing, such as delayed and non-unions, are estimated to occur in
approximately 10-15% of fractures. Delayed healing rates increase to ~50% when the fracture involves vascular
damage or are coupled with high co-morbidity burdens. Current standard of care for impaired healing is surgical
intervention to increase stability or promote healing through application of bone grafts. There are currently no
pharmacological agents approved to accelerate fracture healing or treat malunions. As such there exists an
unmet clinical need for osteoinductive therapeutics that could stimulate bone regeneration through a
non-surgical delivery platform. This proposal builds on recently published work from our group demonstrating
that Nerve Growth Factor (NGF) given therapeutically during the cartilaginous phase of fracture repair promoted
endochondral ossification and accelerated fracture healing. While NGF has not been rigorously studied in long
bone fractures, NGF is well established as a potent regenerative factor within the central and peripheral nervous
system. Multiple clinical trials suggested a therapeutic potential for NGF in treating Alzheimer’s disease and
neuropathies, but the therapy failed to translate due to pain (hyperalgesia) noted upon injection. Recently, our
team has isolated a novel NGF isoform identified from patients that lack nociception due to a point mutation in
the protein (NGFR100W) that fails to transduce pain through an inability to activate the p75NTR signaling pathway.
Since NGFR100W retains TrkA mediated trophic activity, this “painless” NGF presents an exciting opportunity to
revisit the translational potential of NGF. The long-term goal of this grant is to develop and validate a
translationally relevant, non-surgical, therapeutic platform to accelerate fracture repair based on the use
of biodegradable nanowires to provide local and sustained release of “painless” NGF. We accomplish
this through three specific aims. In Aim 1 we tune heparin-coated polycaprolactone-nanowires for the delivery of
NGFR100W and validate this platform can achieve functional activation of the TrkA pathway to promote neuronal
regeneration, while decreasing nociception relative to wild type NGF (NGFWT). We then rigorously test efficacy
of the NGFR100W-nanowires in our clinical target of fracture repair (Aim 2). In parallel we also probe the
mechanism by which NGF/TrkA signaling stimulates fracture repair. This is done in Aim 3 by genetically deleting
the TrkA receptor from specific cell populations to determine whether this pathway is essential for endochondral
fracture repair and if it can be rescued by NGF treatment. These aims allow us to test the central hypothesis
that NGFR100W nanowires will accelerate fracture repair by acting through TrkA signaling to stimulate
chondrocyte-to-osteoblast tr...

## Key facts

- **NIH application ID:** 10630656
- **Project number:** 3R01AR077761-02S1
- **Recipient organization:** STEADMAN PHILIPPON RESEARCH INSTITUTE
- **Principal Investigator:** Chelsea Shields Bahney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $43,428
- **Award type:** 3
- **Project period:** 2021-09-21 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10630656

## Citation

> US National Institutes of Health, RePORTER application 10630656, Dual-Delivery of Bioactive and Anti-Microbial Nanowires for Accelerated Bone Repair (3R01AR077761-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10630656. Licensed CC0.

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