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Fusogen Nanomedicine for Peripheral Nerve Repair
This project is directed at the PRMRP Focus Area of development of novel therapies to repair neurosensory damage. The project deliverables are fusogenic nanoparticles (FNPs), comprised of polymeric fusogens (biomaterials that enhance cell membrane fusion) and cholesterol, to synergistically repair injured peripheral nerves. The central hypothesis being tested is that structure-function relationships among novel amphiphilic tyrosine-derived block copolymer surfactants (TyPS) can lead to effective FNPs which will allow immediate re-establishment of axonal continuity and function. This is being enabled by the first thermodynamically based systematic exploration of structure-activity relations for polymeric fusogens. Concurrently, controlled delivery of cholesterol, a natural membrane component with fusogenic properties which is being encapsulated in the TyPS-based FNPs, is for the first time being investigated for repair of severed nerves. The rationale for this project is that, after injuries involving the transection of nerves, anatomical recovery is usually incomplete due to inherently slow nerve regrowth rates and rapid proximal and distal (Wallerian) degeneration of the stumps. Consequently, patients can suffer substantial life-long disability and even chronic pain if a neuroma follows. Among combat wounded US military personnel, nerve injuries are a leading cause of unfitting conditions and each yearover 100,000 civilian trauma patients suffer disabling nerve injuries which incur enormous long-term healthcarecosts. There are currently no fusogens useful for nerve repair approved by the US Food and Drug Administration.
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