# Microscopic Robot-Assisted Axon Regrowth for Rapid Repair of Peripheral Nerve Injuries

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2022 · $237,202

## Abstract

PROJECT SUMMARY
Functional recovery following peripheral nerve injury (PNI) only occurs in about half of all cases, even after state
of the art surgical reconstruction. Generally, poor functional outcomes stem from the inability of current repair
strategies to overcome lengthy regenerative distances. When damaged, axons attempt to reform lost
connections by growing from the proximal side of the injury towards the distal nerve target. Under natural
regenerative conditions, axons grow at a rate of roughly 1 mm/day, which is often too slow to reach distal targets
before regenerative conditions degrade. However, when pulled, axons can grow at least 10x faster. Indeed,
stretch growth is a mechanism both naturally used during development and routinely exploited by macroscale
mechanobioreactors to produce elongated axon tracks for surgical implantation. These characteristics show that
if stretch growth can be adequately controlled, it could enable rapid repair of extremely long neural defects that
would otherwise be impossible to heal. The result would be a paradigm shifting technology for PNI that
dramatically improves patient outcomes. While the feasibility of stretch growth is well established, the key
challenge for adopting it as a clinical solution to PNI is implementing tension on an axon at the injury site in a
way that can tow the neurite to its distal target. Remarkably, recent advances in microfabrication have produced
a new technology capable of performing this difficult task: microscopic robots. These machines can operate fully
autonomously, supply force, take discrete steps and are small enough to directly apply tension to an axon from
within a nerve fiber. Thus, microscopic robots provide a remarkable opportunity to reimagine PNI repair: if
appropriately developed, they could be implanted, attach to axons, and pull them to the distal target, rewiring the
lost connection by application of force. Here we propose developing a new breed of microrobots that can heal
damaged axons by literally pulling them where they need to go. As the first steps towards this goal, we will
systematically accomplish two key objectives: (1) We will fabricate a new generation of microrobots with body
types and locomotion strategies optimized for navigating in tissue. We will study the role of shape, leg position,
gait pattern, and chemical functionalization of the robot's surface to optimize machines for reliable motion in the
body at sufficient rates to support stretch growth. (2) We will apply these optimized robots to “stretch-grow” axons
ex vivo, within biomimetic hydrogels and then within excised nerve segments. We will demonstrate that the robot
can supply sufficient tension to trigger axon stretch growth, that they speed up axon growth enough to have
major clinical impact, and that the resulting axons are healthy, capable of transmitting electrical pulses, and
capable of forming neuromuscular junctions. Combined, these results will provide proof of concept ...

## Key facts

- **NIH application ID:** 10453290
- **Project number:** 1R21EB032168-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Marc Miskin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $237,202
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453290

## Citation

> US National Institutes of Health, RePORTER application 10453290, Microscopic Robot-Assisted Axon Regrowth for Rapid Repair of Peripheral Nerve Injuries (1R21EB032168-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10453290. Licensed CC0.

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