Treatment of Severe Nerve Injury by Nerve Lengthening and End-to-End Repair
Abstract
Overall Research Plan: What is the peripheral nervous system? What happens when it is damaged? The peripheral nervous system is an electrical communication system that connects the central nervous system (CNS; brain and spinal cord) to the rest of the body. These connections occur through structures called nerves, which are like bundles of wires. Nerves play an important role in many bodily functions, including movement and sensation. To move, nerves send signals out from the brain to a person’s muscles, telling them to contract. To sense and react to the world, nerves send signals from sensory receptors back to the brain (such as a signal from the skin indicating heat or pressure). If a nerve is damaged, then signals cannot go to and from the region of the body connected to this nerve. An individual’s muscles are paralyzed, and he or she may have sensory loss. For example, if a nerve in the arm is injured, one’s fingers may not flex to hold a coffee cup, nor sense that the cup is too hot. This leaves a patient unable to perform daily tasks and often creates a sense of frustration and helplessness. What is the unifying, overarching challenge to be addressed? How is this challenge relevant to a critical problem or question in the field of regenerative medicine and/or patient care? A major traumatic injury suffered by military Service members is severe injury to their nerves, for example, during the blast from an explosive. In these cases, a large gap is often created between the end of the nerve still connected to the spinal cord (the proximal end) and the end that is connected to the muscle or sensory ending (the distal end). Communication across the nerve ceases. The overarching challenge to treat such a condition is “peripheral nerve regeneration,” or to regrow a nerve across the nerve gap, so that communication can resume. Unfortunately, the current solutions to severe nerve injury are not very good, and so Service members (eventually Veterans) permanently lose their ability to move and sense. They may also be in a lot of pain. The goal of this study is to improve the recovery of neuromuscular (nerve and muscle) function following traumatic nerve injury. How does the proposed research address the challenge? The current gold standard treatment for severe traumatic nerve injury is to harvest a piece of nerve from somewhere else in the body called an autograft, and use this graft to bridge the gap between the two broken nerve ends. There are several shortcomings with this approach. An extra surgery is required to harvest the nerve, and the original function of that nerve is sacrificed. There may also not be enough donor tissue to bridge a gap. In addition, neurons (the electrical cells within nerves) must regrow from the proximal end of the nerve, into and through the autograft, and into the distal end of the nerve, before reconnecting with its targeted muscle. Many of these neurons get lost along the way, and do not reconnect. So, recovery can be incomplete. Adding to the challenge, if the muscle goes without reconnecting to neurons for too long, it starts to atrophy, or shrink. This makes it even harder to reconnect with a neuron. The proposed research uses a strategy that avoids the use of a graft, thus bypassing the above shortcomings. More details regarding this strategy are provided in the Research Project discussion below. But briefly, our research team has developed a new device that uses tension (stretch) to coax the proximal nerve end to lengthen (grow) towards the distal nerve end. When the nerve ends are close enough, a surgeon then directly stitches the nerve ends together (“end-to-end” repair), a procedure that typically results in improved recovery compared to a graft. The proposed research also uses a strategy to prevent muscle atrophy, by injecting a new material, called a skeletal muscle hydrogel, into muscles that have lost their nerve input. These strategies
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010510
Entities
People
- Sameer B Shah
Organizations
- United States Army
- University of California, San Diego