Major peripheral nerve injury (PNI) is classified as an injury with a long defect (?3cm) or occurring proximally,requiring long regenerative distances of the host nerve to distal structures (distal nerve, target muscle, etc.).These features result in minimal, if any, functional regeneration as the distal nerve and muscle often degeneratebefore the host nerve is able to reinnervate these structures due to inherently slow regeneration rates. Sincecurrent standard clinical practices delay repairing nerve injuries until the patient (in cases of polytrauma) or theinjury site is stabilized, functional recovery is often extremely limited. In order to maintain the innervationcapability of nerves and muscles following injury, the team at Axonova Medical has developed a proxy for thesedegenerating axons to maintain or "babysit" the distal structures until the host axons are able to reinnervate thedistal targets. This product, the tissue engineered neuromuscular interface (TE-NMI), consists of axon tractsspanning a discrete population of neurons within a hydrogel column. Notably, the diameter of TE-NMIs isdesigned to be on the scale of micrometers, making them easily injectable to facilitate incorporation into currentstandard of care practices in the clinic. In pre-clinical rodent studies, TE-NMIs have been seen to extend axonsinto distal structures post implantation, resulting in babysitting of distal nerve and muscle, therefore keeping itreceptive to eventual host axon reinnervation.Previously, laboratory-grade TE-NMIs have been fabricated using primary rat and porcine neurons as well ashuman induced pluripotent stem cell (iPSC)-derived neurons. In this study, a clinical product will be developedand characterized using GalSafe® neurons as the starting biomass. GalSafe® tissue is an FDA-approvedxenogeneic source produced by Revivicor, Inc. Revivicor has genetically engineered swine to produce tissuelacking a carbohydrate, known as ï¡-galactosidase, that is known to play a key role in eliciting an immuneresponse in humans. GalSafe® neurons are harvested from the spinal cords of GalSafe® swine embryo, and isthe chosen biomass for Axonova's other product, tissue engineered nerve grafts (TENGs). For this proposal,initial characterization and a preliminary in vivo study to determine the efficacy of TE-NMIs to promote recoveryin a chronic axotomy model in swine will be carried out. Successful execution of these studies will acceleratepreclinical safety and efficacy studies and will be incorporated in Axonova's IND application. Overall, TE-NMIshold promise in transforming the field of nerve repair by significantly increasing the clinical window for PNI repair.
Public Health Relevance Statement: PROJECT NARRATIVE
Peripheral nerve injury (PNI), especially those that are long defects or proximal injuries requiring long
regenerative distances, often result in poor functional recovery, leading to a drastic decrease in quality of life.
Due to the inherently slow rate of regeneration in the nervous system, distal nerve structures and muscles are
rendered incapable of reinnervation over time. To address this need, we have developed a potentially
transformational approach to maintain the distal structures and the pro-regenerative environment using
implantable tissue engineered neuromuscular interfaces (TE-NMIs) so that effective reinnervation can occur,
even in cases where repair of the damaged nerve is delayed, thus leading to increased functional recovery.
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