Although the exact mechanisms involved in the growth of axons is still incompletely understood, it is clear that force is a crucial factor for both axonal guidance and lengthening. Indeed, there is a growing body of evidence indicating the importance of physical stimuli for neuronal growth and development. Results of published experimental studies indicate that forces, when carefully controlled, act as powerful stimulators of axonal lengthening. This proposal seeks to develop, test and evaluate a practical implementation of this concept. Specifically, it aims to establish a novel approach for the application of a controlled tensile force to neurones and axons in order to accelerate nerve regeneration after peripheral nerve injury. The methodology based on the use of magnetic nanoparticles (MNPs) and magnetic field, meets the pre-requisites for eventual translation to clinical practice as both components - static magnetic fields and MNPs - are in established use, the first in magnetic resonance imaging (MRI) and the latter as MRI contrast agents and Fe therapy. The research group which I lead has demonstrated in a neuron-like cell line (PC12) that MNPs can direct the neurite outgrowth along the direction imposed by an external magnetic field. This proposal will translate this concept into a model of regeneration of peripheral nerve.
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