Multimodal Approach to Improve Functional Recovery Following Acute and Delayed Peripheral Nerve Injury Repair
Abstract
This research is directed toward the Armed Forces Institute for Regenerative Medicine III, AFIRM III, efforts into addressing Peripheral Nerve Injuries (PNIs). Specifically, this is research to evaluate the feasibility of a very promising polyethylene glycol PEG-fusion therapeutic strategy to dramatically improve outcomes to PNIs from single laceration injury or gap (segmental ablations). Ablation PNIs are particularly common in combat. Military or civilian personnel with ablation PNIs have especially poor recoveries due to: (1) immediate loss of axonal integrity so that action potentials are no longer conducted across the lesion sites; (2) immediate loss of sensation and muscle function in affected limb; (3) Wallerian degeneration of distal axons within 1-3 days; (4) slow and poor recovery of sensation and function that occurs only by 1-2 mm/day outgrowths from proximal axons; (5) atrophy of muscles before reinnervation can occur. Ablation PNIs are currently repaired by suturing (neurorrhaphy) of autografts, donor acellular nerve allografts, or synthetic conduits. Viable-cell nerve transplants in a non-protected host immune environment as alternatives are rapidly rejected because of T cell adaptive responses and/or by innate antigen-independent proinflammatory events, even with immune suppression and major histocompatibility complex (MHC) matching. This research is directed toward: (1) Optimizing PEG Fusion surgical technique translation through understanding the best large animal nerve models (Porcine and Non-human Primate); (2) Increasing the reliability of PEG Fusion process by means of manipulating surgical coaptation and affecting the local immune environment; (3) Evaluating the best combination of techniques and adaptations to inform our partner human clinical trial.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1192652
Entities
People
- Joseph F. Alderete
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine