# mRNA-containing fibrous conduits for repair of long-gap peripheral nerve injury

> **NIH VA I21** · STRATTON VETERANS ADMIN MEDICAL CENTER · 2024 · —

## Abstract

Project Summary/Abstract
Peripheral nerve injury remains a significant problem in the United States and among the Veteran population.
Even after decades of research, there are few clinically available approaches to treat long-gap peripheral nerve
injury. Often, long-gap peripheral nerve repair is facilitated through harvest and placement of sural nerve
autografts into the injury site. Sural nerve isolation induces donor site morbidity, and some patients are unable
to donate neural tissue due to other co-morbidities (such as diabetes). As alternatives to the autografts, nerve
allografts and biomaterial scaffolds have emerged as possible approaches to supplant the autograft. However,
allografts require extensive decellularization processes, and it is challenging to find size-matched allografts for
patients. Biomaterial conduits can be shaped into appropriate sizes. Many biomaterial conduits lack sufficient
extracellular matrix to promote extensive regeneration of axons. In total, autograft, allograft, and biomaterial
strategies routinely fail to completely rescue lost function. Thus, new strategies are needed to advance the
field. Biomaterial conduits that consist of aligned, electrospun fibers robustly promote axonal regeneration in
preclinical models of peripheral nerve injury. Fibrous materials are produced using synthetic, degradable
polymers that contain no extracellular matrix. Schwann cells migrating into the injury site are responsible for
producing sufficient ECM to foster robust regeneration. Unfortunately, Schwann cells immediately after
peripheral nerve injury reduce their production of key growth factors, such as neurotrophin-3 (NT-3). Therefore,
Schwann cells are unable to produce sufficient factors to create ECM and growth factors to robustly induce
regeneration. Inclusion of exogenous stem cells and Schwann cells that release regenerative factors or use of
biomaterials that release growth factors improve regeneration in preclinical models. However, cellular explants
from donor tissue require immunosuppression, and it is difficult to release proteins from degradable polymers
(which typically require harsh chemicals for polymer synthesis). Harsh chemicals used to fabricate biomaterial
scaffolds denature growth factors, requiring investigation of alternative approaches. In this SPiRE application,
we propose to develop mRNA-releasing fibrous scaffolds and assess the ability of the mRNA-releasing
scaffolds to promote peripheral regeneration in a pre-clinical injury model. In total, the development of new
biomaterial approaches to treat peripheral nerve injury may lead to new tools capable of promoting robust
peripheral nerve regeneration for the Veteran population.

## Key facts

- **NIH application ID:** 10869875
- **Project number:** 5I21RX004406-02
- **Recipient organization:** STRATTON VETERANS ADMIN MEDICAL CENTER
- **Principal Investigator:** Ryan J. Gilbert
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-01-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869875

## Citation

> US National Institutes of Health, RePORTER application 10869875, mRNA-containing fibrous conduits for repair of long-gap peripheral nerve injury (5I21RX004406-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10869875. Licensed CC0.

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