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Longitudinal Single-Axon-Resolution Imaging of Peripheral Nerve Injury Response in Mice Using an Optical Window

Igor D Luzhansky^1,2, Emma Anisman², Ron Perez^1,3

¹Institute of Materials Science and Engineering, Washington University in Saint Louis, St. Louis, USA.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)

|June 28, 2026

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Researchers developed a new imaging method for peripheral nerve repair. A flexible window allows high-resolution, long-term visualization of nerve regeneration in vivo, aiding the study of nerve injury and therapies.

Area of Science:

Neuroscience
Biomedical Engineering
Regenerative Medicine

Background:

Chronic, high-resolution imaging of peripheral nerve injury and regeneration is challenging due to optical inaccessibility.
Peripheral nerves are embedded in soft tissue, limiting in vivo visualization.

Purpose of the Study:

To develop a broadly applicable approach for longitudinal, high-resolution optical imaging of peripheral nerves in vivo.
To overcome the technical challenges of imaging peripheral nerve regeneration.

Main Methods:

Implantation of a flexible, optically transparent polydimethylsiloxane (PDMS) window above the mouse sciatic nerve.
Utilizing multimodal microscopy including confocal, two-photon, and second-harmonic generation microscopy.
Simultaneous visualization of axons, Schwann cells, collagen, and vasculature.

Keywords:

PDMS window Schwann cells axonal degeneration intravital microscopy live animal imaging multimodal imaging peripheral nerve regeneration sciatic nerve second‐harmonic generation (SHG)two‐photon (2P) microscopy

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Main Results:

The PDMS window provided stable, motion-tolerant optical access for over one month without impairing nerve function.
Enabled real-time tracking of axonal degeneration, regeneration, Schwann cell dynamics, and extracellular matrix-guided axon pathfinding.
Supported longitudinal imaging of axonal regrowth in a nerve transection gap repair model.

Conclusions:

The developed platform enables new avenues for studying peripheral nerve biology in vivo.
Facilitates the testing and development of novel regenerative therapies for peripheral nerve injuries.
Offers a significant advancement in visualizing nerve regeneration processes.