Nerve Repair with Polyethylene Glycol to Promote Rapid Return of Nerve Function
Abstract
Background: Nerve Injuries to the upper and lower extremities are very common in the United States, occurring in over 700,000 cases annually. In the military, there is a greater than 90% chance of survival from a battlefield injury. Unfortunately, the increasing rate of survival means that more wounded Warriors are living the rest of their lives with injured arms and legs or amputations. Most of these injuries involve damage to nerves. Repair after nerve injury is completely dependent upon the success of nerve regrowth. Nerves grow very slowly, at a rate of about 1 inch per month. Damaged nerves near the shoulder must grow a long distance to reach arm and hand muscles. In fact, when combined with bone and vascular injury, recovery after severe arm or leg nerve injury is so poor that amputation may be considered for these patients. Polyethylene glycol (PEG) is a component within a solution used commonly in medical practice today. In animal studies, PEG improves the healing of nerve injury sites by immediate fusion of the cut nerve. We have used PEG in our lab to demonstrate that we can dramatically improve nerve function after injury in rats and in early human studies. This study will help demonstrate if PEG fusion works as well in human nerve injuries as it does in animal models to return early function after simple nerve injury and in cases with large portions of the nerve lost due to trauma. Overall Objective: This study is designed to test PEG-based nerve repair for simple repairs or, with nerve grafts, to treat nerve injuries with nerve gaps. We will determine whether nerve repairs with PEG fusion will be more successful than repairs without PEG. We will use nerve grafts taken from the patient in areas where nerves are available to sacrifice to bridge traumatic nerve gaps to help regain essential upper extremity nerve function. Focus Area: Development of advanced tissue regeneration therapeutics in nerves for the restoration of traumatically injured extremities. Specific Objectives: 1. Determine whether delivery of PEG with nerve repair is superior to repair alone for sensory nerve defects in human nerve injuries. 2. Determine whether delivery of PEG with nerve grafts is superior to graft alone for up to 3 cm nerve defects in human upper extremity nerve injuries. Risks: Our technology applies PEG to the site of nerve repair. This medication is already being used in humans for many different applications and has already been applied to a small group of human nerve repairs with no adverse effects. In animal studies, the solution applied in the intended manner caused no harm. For these reasons we feel the eventual risk to people that would undergo this therapy is minimal; however, the goal of this proposal is to demonstrate efficacy in human nerve injuries. Military Benefit: Traditional nerve repair techniques rely on axons (i.e., neurons) growing from the site of injury to the area to be innervated, this distance can be up to a meter in humans. This is a very slow process and may take literally years to occur while muscle atrophies resulting in permanent loss of function. PEG-based cell fusion repair of axons relies on a fundamentally different mechanism. With this technique, the severed proximal and distal stumps of axons are rejoined to recreate, almost immediately, a functional nerve. This is analogous to soldering a cut wire back together rather than relaying an entirely new cable. No other method is known to cause an immediate fusion of cut nerves and a resulting near immediate recovery in patients. We have shown the surgical repair of nerves when supplemented with this solution shows immediate restoration of nerve conduction and, in the weeks that follow, leads to observable improvement of functional outcomes in treated animals. If this technique can be successfully applied clinically, this new protocol will fundamentally change the way nerve injury is treated. PEG fu
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110441
Entities
People
- Wesley P Thayer
Organizations
- United States Army
- Vanderbilt University