Fusogens: Chemical Agents That Can Rapidly Restore Function After Nerve Injury.

BACKGROUND: Restoring function after nerve injury remains one of medicine's greatest challenges. The current approach of epineurial coaptation does not address the fundamental insult at the molecular level: a discontinuity in the axonal membranes. Membrane fusion is possible through agents collectively called chemical fusogens, which are heterogeneous in structure and mechanism of action. We sought a unifying system for classifying fusogens to better understand their role in cell fusion. MATERIALS AND METHODS: We conducted a comprehensive literature review to identify the most commonly cited chemical fusogens, their structures, mechanisms of actions, and clinical applications to date. We identified seven chemical fusogens (polyethylene glycol, chitosan, dextran sulfate, n-nonyl bromide, calcium, sodium nitrate, and H-α-7), which have each been studied to different extents in protoplasts, animals, and humans. RESULTS: Chemical fusogens achieve cell fusion by one of two ways: bringing cells in close enough proximity to each other so the inherent fluidity of the phospholipid membrane allows for their rearrangement or modifying the surface charges of the membranes to diminish repellent charges. Sowers initially put forth a classification system that identified these agents as cell aggregators and membrane modifiers, respectively. We adapted this classification system in the setting of axonal membrane fusion and hypothesized that the most effective approach to axonal membrane repair is likely combination of both. CONCLUSIONS: Chemical fusogens could be grouped into two mechanistic categories-cell aggregators and membrane modifiers. For axonal membrane fusion, a combination of both mechanisms can significantly contribute to advancing outcomes in peripheral nerve repair via a chemical-surgical intervention.