# Dental Stem Cells and Scaffold-free Tissue Engineering to Enhance Facial Nerve Regeneration

> **NIH NIH R56** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $341,467

## Abstract

The overall goal of this study is to accelerate regeneration and improve functional outcomes in facial nerve
injuries using novel scaffold-free dental pulp cell constructs. Facial nerve injuries severely impact patient
quality of life by impairing motor function and causing facial paralysis. The severity of facial nerve injury
dictates treatment modality where mild injuries are treated with end-to-end suturing, and the treatment of more
severe injuries involves replacing damaged tissue with autologous nerve grafts; however, these therapies
require a prolonged repair time and full functional recovery is not achieved. This is due in part to diminished
Schwann cell (SC) support. SCs, neural crest-derived glial cells, provide neurotrophic factors (NTFs), which
are known to promote neuron survival and axon extension. The dental pulp, the soft tissue found at the center
of the tooth, contains a population of adult stem/progenitor cells that also endogenously express high levels of
NTFs, a characteristic attributed to their neural crest origins. Furthermore, dental pulp cells (DPCs) can be
induced to differentiate towards a SC-like phenotype, which further enhances NTF expression. We have
developed scaffold-free DPC sheets that can be applied for enhancing nerve regeneration in both mild or
severe injuries. For mild injury, DPC sheets can be wrapped around injured nerves treated using standard
methods to act as localized NTF delivery systems to enhance outcomes. In more severe injuries, DPC sheets
can be coaxed into solid, cylindrical tissues that function as conduits that provide a bioactive alternative to
autografts. In the latter, DPCs are induced to generate an aligned ECM; therefore, these conduits provide both
trophic cues (NTFs) that promote axon regeneration and guidance cues (aligned ECM) that orient axonal
growth. Our preliminary data establishes that DPC sheets express high levels of NTFs sufficient to induce
neurite outgrowth in neuronal cells in vitro, and enhance regeneration in rat facial nerve crush injury in vivo.
Moreover, when cultured on a micro-grooved substrate, DPC sheets produce an aligned ECM that effectively
orients neurite extension in vitro. In Specific Aim 1, we will evaluate if inducing SC differentiation will further
enhance the regenerative effects of DPC sheets in vitro. We hypothesize that SC-differentiated DPC sheets
will have greater NTF expression and induce greater neurite outgrowth in primary dorsal root ganglion cells in
vitro than un-induced DPC sheets. In Specific Aim 2, we will test if wrapping an end-to-end sutured transection
nerve injury with a DPC sheet will enhance axon regeneration and functional recovery relative to untreated
controls. In Specific Aim 3, DPC cell sheets, comprising an aligned ECM, will be rolled in solid, cylindrical
conduits and used to bridge segmental injuries in the rat facial nerve. The ability of these conduits to support
axonal regeneration and improve nerve functional recovery wi...

## Key facts

- **NIH application ID:** 10453479
- **Project number:** 1R56DE030881-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Fatima Naz Syed
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $341,467
- **Award type:** 1
- **Project period:** 2021-08-12 → 2022-08-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453479

## Citation

> US National Institutes of Health, RePORTER application 10453479, Dental Stem Cells and Scaffold-free Tissue Engineering to Enhance Facial Nerve Regeneration (1R56DE030881-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10453479. Licensed CC0.

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