Magnetothermal Modulation of Calcium-Dependent Nerve Growth

Abstract

Nerve injuries are common, and the available treatments including invasive surgeries do not guarantee complete regeneration of the injured nerves and restoration of function. Despite the ability of peripheral nerves to regenerate, the slow rate of axonal growth hampers the functional recovery. Development of new approaches to discover underlying mechanisms that may accelerate axonal growth is needed to overcome these limitations and augment available treatments of nerve injury. In addition to chemical factors, recent studies suggested the use of optogenetics and electrical stimulation to promote axonal growth. The underlying mechanisms of these approaches, however, require further investigation. Furthermore, their application relies on invasive hardware, which may not be compatible with injured nerves under significant mechanical deformation. Here, it is shown that thermal activation of a heat sensitive ion channel TRPV1 promotes axonal growth in a calcium-dependent manner. By leveraging heat dissipation of magnetic nanoparticles in alternating magnetic fields, the calcium influx through TRPV1 channels endogenously expressed in dorsal root ganglion explants is triggered remotely. The accelerated axonal growth through elongation of neurofilaments and increased Schwann cell migration following magnetothermal stimulation is observed. These findings suggest future applications of magnetothermal modulation of axonal growth as a minimally invasive approach to accelerate nerve regeneration.