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Peer-reviewedCC BY 4.0Advanced Science

Mechanical Distraction Engages a Neuro‐Immune Program to Drive Regenerative Soft‐Tissue Healing in Ilizarov Bone Transport

  • Yueliang Zhu1,2,3
  • Jiayu Chen1,2,3
  • Xuehuan Wen4
  • Kaijia Tang1,2,3
  • Ling Gao1,2,3
  • Chenxing Wang1,2,3
  • Yixuan Feng5
  • Si‐He Qin6
  • Tao Chen1,2,3
  • Xiaohua Yu1,2,3
6 affiliations
  1. 1Department of Orthopedic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang People's Republic of China
  2. 2Orthopedics Research Institute of Zhejiang University Hangzhou Zhejiang People's Republic of China
  3. 3Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province Hangzhou Zhejiang People's Republic of China
  4. 4Department of Oncology The People's Hospital of Cangnan Zhejiang Wenzhou Medical University Wenzhou Zhejiang People's Republic of China
  5. 5Eye Center of Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang People's Republic of China
  6. 6Department of Orthopedic Surgery Rehabilitation Hospital Affiliated to National Research Center for Rehabilitation Technical Aids Beijing People's Republic of China
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Abstract

The Ilizarov bone transport technique reproducibly accelerates soft‐tissue healing around the distraction zone through an unexplained mechanism. Using a rat dynamic bone transport (DBT) model, we test whether a sensory neuro‐immune axis links sustained mechanical distraction to tissue regeneration. DBT induced sensory reinnervation and established a calcitonin gene‐related peptide (CGRP)‐rich neurotrophic niche, which reorganized early inflammation and promoted vascular–epithelial expansion. Bulk RNA‐seq revealed a neurodevelopmental transcriptional program, while single‐cell RNA‐seq showed reduced inflammatory myeloid subsets and expansion of reparative Arg1+ macrophages and protective neutrophil states. Capsaicin ablation of transient receptor potential vanilloid 1‐positive (TRPV1+) sensory fibers abolished these transitions and DBT‐enhanced repair, and local CGRP receptor blockade substantially attenuated it. We propose that the upstream step is mechanosensory; however, this component is a framework supported by correlative expression data, including Piezo1 detection in wound macrophages, and by functional perturbations of sensory nerves. Local strain was not measured, and direct mechanotransduction at the cellular level remains to be demonstrated. These findings indicate that Ilizarov‐type distraction engages a sensory neuro‐immune program that orchestrates inflammation resolution and soft‐tissue regeneration, providing a mechanistic framework for a long‐standing clinical observation.

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Cite

BibTeXRIS
BibTeX
@article{zhu2026mechanical,
  title = {{Mechanical Distraction Engages a Neuro‐Immune Program to Drive Regenerative Soft‐Tissue Healing in Ilizarov Bone Transport}},
  author = {Yueliang Zhu and Jiayu Chen and Xuehuan Wen and Kaijia Tang and Ling Gao and Chenxing Wang and Yixuan Feng and Si‐He Qin and Tao Chen and Xiaohua Yu},
  journal = {Advanced Science},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.78382},
  url = {https://doi.org/10.1002/advs.78382},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Mechanical Distraction Engages a Neuro‐Immune Program to Drive Regenerative Soft‐Tissue Healing in Ilizarov Bone Transport
AU  - Yueliang Zhu
AU  - Jiayu Chen
AU  - Xuehuan Wen
AU  - Kaijia Tang
AU  - Ling Gao
AU  - Chenxing Wang
AU  - Yixuan Feng
AU  - Si‐He Qin
AU  - Tao Chen
AU  - Xiaohua Yu
PY  - 2026
DA  - 2026/10/25
JO  - Advanced Science
DO  - 10.1002/advs.78382
UR  - https://doi.org/10.1002/advs.78382
AB  - The Ilizarov bone transport technique reproducibly accelerates soft‐tissue healing around the distraction zone through an unexplained mechanism. Using a rat dynamic bone transport (DBT) model, we test whether a sensory neuro‐immune axis links sustained mechanical distraction to tissue regeneration. DBT induced sensory reinnervation and established a calcitonin gene‐related peptide (CGRP)‐rich neurotrophic niche, which reorganized early inflammation and promoted vascular–epithelial expansion. Bulk RNA‐seq revealed a neurodevelopmental transcriptional program, while single‐cell RNA‐seq showed reduced inflammatory myeloid subsets and expansion of reparative Arg1+ macrophages and protective neutrophil states. Capsaicin ablation of transient receptor potential vanilloid 1‐positive (TRPV1+) sensory fibers abolished these transitions and DBT‐enhanced repair, and local CGRP receptor blockade substantially attenuated it. We propose that the upstream step is mechanosensory; however, this component is a framework supported by correlative expression data, including Piezo1 detection in wound macrophages, and by functional perturbations of sensory nerves. Local strain was not measured, and direct mechanotransduction at the cellular level remains to be demonstrated. These findings indicate that Ilizarov‐type distraction engages a sensory neuro‐immune program that orchestrates inflammation resolution and soft‐tissue regeneration, providing a mechanistic framework for a long‐standing clinical observation.
SN  - 2198-3844
ER  -