Specialized storage technology for preserving axonal viability

A specialized calcium-free solution preserves peripheral nerve axons for up to nine days at low temperatures, enhancing nerve graft viability for effective repair of injuries using polyethylene glycol fusion, promoting rapid sensory and motor recovery.

Background

Peripheral nerve injuries (PNIs) often result in segmental-loss defects, leading to immediate loss of sensory and motor functions, followed by Wallerian degeneration (WD) of severed axonal segments. Current repair strategies, such as autografts, allografts, and synthetic conduits, fail to prevent WD and rely on natural regeneration, which is slow and often results in poor functional recovery. These methods are further complicated by issues such as immune rejection and the lack of supporting cells in acellular grafts. Traditional storage solutions for nerve grafts, focus on preserving structural integrity rather than axonal function, leading to rapid axonal degeneration.

The challenge lies in developing storage solutions that maintain axonal viability, which is crucial for successful nerve repair techniques like polyethylene glycol (PEG) fusion, known for its ability to rapidly restore function without immune suppression. Current solutions often fail to preserve axonal function, highlighting the need for optimized storage conditions that can extend the viability of nerve grafts and improve outcomes for nerve repair procedures.

Technology description

The specialized storage solution for peripheral nerve grafts is a calcium-free formulation designed to maintain axonal viability during ex vivo storage. It comprises sodium chloride, sodium acetate anhydrous, sodium gluconate, potassium chloride, and magnesium chloride, with an osmolarity of 250-255 mOsm per liter.

This solution is optimized for low-temperature storage (4°C), effectively preserving the conduction of compound action potentials and the structural integrity of axons and myelin for up to nine days. This preservation is crucial for successful polyethylene glycol (PEG) fusion techniques, which repair segmental-loss peripheral nerve injuries by fusing viable donor axons with host axons, preventing Wallerian degeneration and promoting rapid recovery of sensory and motor functions.

This technology is differentiated by its specific composition and reduced tonicity, which enhance axonal survival compared to traditional solutions and normal saline. The absence of calcium is a key factor, as calcium can induce granular disintegration of axoplasmic structures. The solution’s ability to maintain axonal viability significantly extends the storage time of peripheral nerve grafts, enabling the establishment of tissue banks and facilitating the use of stored grafts in nerve repair. Additionally, PEG-fused grafts are immune-tolerated without the need for tissue matching or immune suppression, offering a novel approach to addressing the shortage of transplantable nerve grafts and improving outcomes in nerve injury repairs.

Benefits

Preserves axonal viability for up to nine days, enabling successful nerve grafts
Prevents Wallerian degeneration, promoting rapid recovery of sensory and motor functions
Facilitates PEG-fusion of donor and host axons, enhancing nerve repair outcomes
Allows for the establishment of PNVA tissue banks, addressing nerve graft shortages
Immune-tolerated without tissue matching or immune suppression, reducing rejection risks
Optimizes storage solutions for other organ/tissue transplants, potentially improving preservation techniques