# Predegenerating donor nerve for grafting using focused ultrasound neurotomy

**Authors:** Tak-Ho Chu, Nicolas Lasaleta, Siyun Li, Amanda McConnachie, Leonardo Molina, Saud Alzahrani, Laura Curiel, Samuel Pichardo, Rajiv Midha

PMC · DOI: 10.1038/s41598-025-00316-8 · 2025-05-04

## TL;DR

This study explores using focused ultrasound to predegenerate nerves for grafting, finding it feasible but with limited benefits over fresh grafts in nerve repair.

## Contribution

A non-invasive method using HIFU to induce Wallerian degeneration in nerves for grafting is proposed and tested.

## Key findings

- HIFU successfully induced focal thermal lesions and Wallerian degeneration in sciatic nerves.
- Predegenerated grafts showed no significant behavioral or histomorphometric advantages over fresh grafts.
- Soleus muscle weight was higher in animals with predegenerated nerve grafts.

## Abstract

Early experimental evidence suggests that predegenerated nerve graft enhance axonal growth compared to freshly harvested nerve graft in nerve gap repair. However, the practicality of surgically pre-conditioning nerves for grafting remains a major obstacle. Herein, we aim to investigate the feasibility of focal lesioning of nerve tissue using high-intensity focused ultrasound (HIFU) and compare the regenerative effects of predegenerated nerve grafts to freshly harvested grafts in a rat sciatic nerve transection and repair model. As a proof of principle, sciatic nerves were exposed for HIFU lesioning to increase targeting accuracy. HIFU induced focal thermal lesioning to the sciatic nerve, resulting in p75 and cJun up-regulation at the distal segment observed at 7 days post-sonication. All behavioural outcome metrics including von Frey sensory test and walking gait were similar between animals with freshly harvested and predegenerated nerve grafts except soleus muscle weight was significantly higher in the latter group. As well, similar axon histomorphometric results were found in 2-week survival animals. Our findings showed that it is possible to induce Wallerian degeneration in distal nerve for grafting using non-invasive HIFU. However, limited beneficial effects of predegenerated grafts were obtained compared to freshly harvested grafts in nerve gap repair.

The online version contains supplementary material available at 10.1038/s41598-025-00316-8.

## Linked entities

- **Genes:** CUX1 (cut like homeobox 1) [NCBI Gene 1523], JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725]
- **Species:** Rattus norvegicus (taxon 10116), Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Ngfr (nerve growth factor receptor) [NCBI Gene 24596] {aka LNGFR, RNNGFRR, Tnfrsf16, p75, p75NTR}
- **Diseases:** Wallerian degeneration (MESH:D014855), nerve transection (MESH:D020221)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12050296/full.md

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Source: https://tomesphere.com/paper/PMC12050296