Prototype Solutions for Peripheral Nerve Injury

The overarching goal of this program is to provide biomanufacturing and/or development of a device, biologic, or combination prototype that aims to maintain, re-establish or regenerate myoneural connections.

The Awardee will develop an innovative solution to a critical problem in nerve regeneration or end-organ health. Applications were expected to address one or more of the following focus areas in nerve regeneration or end-organ health:

  1. Maintenance of the post-synaptic junction in denervated muscle.
  2. Re-establish myoneural connections in the periphery.
  3. Co-regeneration of nerve and muscle

This effort aims to promote highly innovative, groundbreaking research; high-impact research with near-term clinical relevance; multidisciplinary, synergistic research; and translational studies to support the fluid transfer of knowledge from basic principles to clinical solutions.

The research project award recipients were selected from the Offerors who responded to MTEC’s Request for Project Proposals (18-05-PeripheralNerve).

Title of Project: Injectable Gel for Restoration of Myoneural Function following Peripheral Nerve Injury
Project Team: Renerva, LLC and Cornell University
Award Amount: $2,436,899
Project Duration: 3 years
Project Objective: The proposed effort will complete preclinical development and begin clinical development of Renerva Peripheral Nerve Matrix to treat peripheral nerve injury. The proposed effort has four objectives:

1. Perform confirmatory efficacy testing of the fully manufactured product in animal models.

2. Execute additional preclinical testing needed for regulatory submission.

3. Conduct a first‐in‐man clinical trial for the purpose of generating safety and efficacy clinical data.

4. Prepare regulatory submission to seek market clearance/grant in the U.S.

Year 1 Accomplishments:

    • Completed product development.
    • Performed small animal testing and confirmed product efficacy.
    • Initiated pre-clinical testing required by the U.S. Food and Drug Administration (FDA), such as viral inactivation, sterility validation, and biocompatibility studies.
    • Developed documentation for regulatory and clinical trial submission.
    • Engaged resources to perform clinical trials (i.e., investigators, sites, clinical contract research organization, insurance, etc.).

Title of Project: Accelerated Innervation of 3D Bioprinted Muscle Construct with Pre-fabricated Neuromuscular Junctions and Neurotrophic Factor Release System
Project Team: Wake Forest University Health Sciences
Award Amount:  $2,330,000
Project Duration: 3 years
Project Objective: Treatment of extensive skeletal muscle loss due to traumatic injuries, congenital defects, or diseases, such as cancer, is a clinically challenging problem for soldiers and civilians, alike. In the U.S. alone, approximately 4.5 million patients with skeletal muscle injuries undergo reconstructive surgeries each year to restore normal tissue function. In many cases, extensive muscle defect results in functional impairment involving nerve damage, which leads to denervation atrophy and permanent functional disability. The standard of care is autologous muscle flap transfer; however, host muscle tissue availability and donor site morbidity remain challenges. Tissue-engineered muscle has been proposed as a solution to repair volumetric muscle defects and restore muscle function. To achieve functional recovery, engineered muscle constructs, which are analogous to denervated muscle, require rapid integration with the host nervous system. However, current tissue-engineered muscles have not adequately addressed issues related to peripheral nerve regeneration and construct innervation. In this project, we aim to develop an implantable bioprinted engineered muscle prototype with pre-formed neuromuscular junctions (NMJs) and a neurotrophic factor controlled release system to accelerate integration with host nerve. We expect this strategy for muscle bioengineering will accelerate and improve functional recovery of the restored muscle.

Year 1 Accomplishments:

• Successful isolation and culture-expansion of patient-derived skeletal muscle cells.
• Establishment of 3D bioprinting parameters for the generation of muscle tissue constructs containing human muscle progenitor cells.
• Identification of an effective neurotrophic factor combination that promotes nerve growth and migration.

Title of Project: A Novel Cell-based Therapy to Treat Muscle Atrophy Associated with
Peripheral Nerve Injury
Project Team: Nano Terra, Inc.
Award Amount: $2,327,616
Project Duration: 3 years
Project Objective: The proposed effort will complete preclinical development of a neural prosthesis that maintains viability of the neuromuscular junction and preserves muscle health and function while the injured peripheral nerves heal. There are three primary study Objectives: i) optimize efficacy in large animal model, ii) manufacture prosthesis under cGMP; and iii) complete preclinical testing and IND package for regulatory submission.