# Piezoelectric Chitosan Microporous Scaffolds for Ultrasound-Driven Schwann Cell Migration and Enhanced Neurotrophins Production

**Authors:** Marta Bianchini, Francesco Iacoponi, Matteo Battaglini, Gianni Ciofani, Silvestro Micera, Leonardo Ricotti, Eugenio Redolfi Riva, Andrea Cafarelli

PMC · DOI: 10.1021/acsbiomaterials.5c01086 · ACS Biomaterials Science & Engineering · 2025-10-14

## TL;DR

A new piezoelectric scaffold is developed to stimulate Schwann cells using ultrasound, promoting nerve regeneration and neurotrophin production.

## Contribution

A novel piezoelectric chitosan scaffold with barium titanate nanoparticles is introduced for ultrasound-driven Schwann cell migration and neurotrophin enhancement.

## Key findings

- The scaffold's anisotropic pore structure mimics native neural tissue morphology and mechanics.
- Ultrasound stimulation increases Schwann cell migration and neurotrophin production.
- Gene expression analysis shows upregulation of cell motility and regeneration pathways.

## Abstract

Peripheral nerve injuries often result in nerve damage
that significantly compromises functional recovery. Current treatments
have substantial limitations. Engineered nerve guidance conduits emerge
as a promising alternative, but their efficacy is limited when bridging
large gap injuries. Schwann cells, which are essential for nerve regeneration,
require a supportive microenvironment to maintain their regenerative
function. Recent advances in tissue engineering focus on combining
functional biomaterials and external stimuli, such as electrical stimulation,
to achieve nerve guidance conduits that enhance regeneration. This
study presents a piezoelectric chitosan scaffold loaded with barium
titanate nanoparticles, designed for wireless electrical stimulation
of Schwann cells through low-intensity pulsed ultrasound. The scaffold
is engineered with an anisotropic pore microstructure to provide biomimicry.
Morphological and mechanical characterization confirms that the scaffold
exhibits structural properties similar to those of native neural tissue.
Using a highly controlled in vitro ultrasound system, we optimize
stimulation parameters to maximize cell migration and evaluate neurotrophic
factor production. Gene expression analyses reveal the upregulation
of cell motility and regeneration pathways. These findings demonstrate
that ultrasound-activated chitosan scaffolds hold significant potential
as a noninvasive tool for improving nerve regeneration, offering a
comprehensive in vitro analysis to facilitate future preclinical and
clinical translation.

## Linked entities

- **Chemicals:** barium titanate (PubChem CID 159419)

## Full-text entities

- **Genes:** NTF3 (neurotrophin 3) [NCBI Gene 4908] {aka HDNF, NGF-2, NGF2, NT-3, NT3}
- **Diseases:** nerve damage (MESH:D000080902), Peripheral nerve injuries (MESH:D059348)
- **Chemicals:** barium titanate (MESH:C024547), Chitosan (MESH:D048271)

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12807355/full.md

## References

92 references — full list in the complete paper: https://tomesphere.com/paper/PMC12807355/full.md

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Source: https://tomesphere.com/paper/PMC12807355