A New Strategy to Produce Sustained Growth of Central Nervous System Axons: Continuous Mechanical Tension

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Abstract
Although a primary strategy to repair spinal cord and other nerve injuries is to bridge the damage with axons, producing axons of sufficient length and number has posed a significant challenge. Here, we explored the ability of integrated central nervous system (CNS) axons to grow long distances in response to continuous mechanical tension. Neurons were plated on adjacent membranes and allowed to integrate, including the growth of axons across a 50-µm border between the two membranes. Using a microstepper motor system, we then progressively separated the two membranes further apart from each other at the rate of 3.5 µm every 5 min. In the expanding gap, we found thick bundles comprised of thousands of axons that responded to this tensile elongation by growing a remarkable 1 cm in length by 10 days of stretch. This is the first evidence that the center portion of synapsed CNS axons can exhibit sustained "stretch-induced growth." This may represent an important growth mechanism for the elongation of established white matter tracts during development. We also found by doubling the stretch rate to 7 µm/5 min that the axon bundles could not maintain growth and disconnected in the center of the gap by 3 days of stretch, demonstrating a tolerance limit for the rate of axonal growth. We propose that this newfound stretch-induced growth ability of integrated CNS axons may be exploited to produce transplant materials to bridge extensive nerve damage.