PI: Kacey Marra
Title: Development of an Implantable Medical Device for Human Extremity Nerve Injuries
Description: Arm, leg, and nerve-related injuries are among the most common injuries sustained by our brave Warfighters. Battlefield extremity injuries are often more severe than civilian, thus highlighting a need for therapies that treat extensive peripheral nerve injuries. Most challenging of these are the healing of long-gap peripheral nerve injuries (i.e., nerve gaps greater than 1 inch). When there is a long-gap nerve injury, the current solution is to relocate a nerve from one part of the body to where the nerve gap exists, a surgical practice known as “autograft.” This treatment involves secondary concerns of additional surgical incisions and complications such as infection, prolonged operating times, longer anesthesia burden; and potential effects of permanent numbness where the nerve was removed. Additionally, autografting may not be an option for everyone, as patients with multiple injuries may not have access to acquire a “donor” nerve from an uninjured extremity. There are a few medical devices, known as nerve guides or tubes, that can regrow nerve gaps less than 1 inch long; however, they are not FDA-approved for use in long nerve gaps. Indeed, the need for a commercially available nerve guide to repair peripheral nerve gaps is significant. This need is addressed in our current work of a creative of an off-the-shelf nerve guide, called AxoMax nerve guide. Our patented technology utilizes a tube that can safely break down in the body, and also contains a controlled drug delivery system that gives the cues necessary for the regrowth of nerves over long gaps. We have conducted both large and small animal studies that demonstrate AxoMax can heal these nerve gaps and now plan to safely demonstrate this action in humans. This project addresses the following Topic Area: Sustained-Release Drug Delivery, within this Area of Encouragement: Research into techniques to provide sustained release of drugs in tissue repair applications, such as bone or nerve regeneration.
This project will allow the team of doctors and scientists to use an established current Good Manufacturing Practices (cGMP) laboratory at the Mayo Clinic to prepare AxoMax guides that will be used in future clinical trials. In order to test the nerve guides in humans, we will need to get regulatory approval from the FDA. In order to obtain FDA approval, we need to develop a reproducible fabrication protocol for large inner diameter AxoMax nerve guides of varying length. We have created an automated machine that we have been using to reproducibly manufacture nerve guides. This machine can be transferred to the Mayo Clinic’s cGMP facility for the large-scale production of nerve guides. In Aim 1, we will validate the machine using the aforementioned mechanical characterization, biocompatibility assays, and release kinetics to be performed on the guide. We will complete cGMP scale-up and process validation and manufacture nerve guides at the cGMP facility for biocompatibility tests, sterilization validation and packaging validation, and shelf-life tests. In Aim 2, we will validate the design process for large nerve guides following FDA regulations and assemble a Design History File. There are numerous issues to address prior to applying for regulatory approval. This includes such quality management activities like meeting design inputs with design processes and design outputs, and most importantly, meeting user needs with validation data, thereby necessitating an Investigational Device Exemption (IDE)-based clinical investigation. Thus, in Aim 2 will validate the nerve guide design in the clinical setting, assessing user specification using the larger nerve guides.
We have been developing this off-the-shelf nerve guide for over 10 years and have established the efficacy of the nerve guide in a non-human primate nerve defect model, successfully bridging a 2-inch nerve gap. We are deeply committed to examine the nerve guide in humans immediately following the completion of this 2-year technology development project. Our preclinical data can support basic device functionality and address significant safety concerns for this device. We will further refine and develop the AxoMax nerve guide so that it can be examined in a clinical trial, followed by future commercialization.
Source: DoD CDMRP PRMRP TTDA
Term: July 1, 2021-June 30, 2023
Amount: $2,085,067