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.

Magnetic nanomaterials‐mediated neuromodulation

“…This transgene‐free magneto‐thermally controlled release of adrenal hormones will no doubt precipitate advances in understanding the biology of stress and in developing treatments for stress‐related psychiatric disorders. It certainly seems that other hormones in other TRPV1‐expressing organs can be similarly regulated by MNMs‐based stimulation methods without involving gene transfection, offering potential for future clinical use (Maeng et al, 2022; Rosenfeld et al, 2022).…”

Functional material-mediated wireless physical stimulation for neuro-modulation and regeneration

“…By converting magnetic fields into thermal signals, magnetic nanoparticles (MNPs) have opened up possibilities for non-invasive neural thermal stimulation techniques with highly precise nanoscale spatial resolution. 210 The heating effect of MNPs is caused by the work done by magnetic torque on the dissipative forces during the cyclic response of magnetization. 211 Ranging from 100 kHz to 1 MHz, 212 the hysteresis-heating alternating field is the most widely used magnetic field.…”

“…211 Ranging from 100 kHz to 1 MHz, 212 the hysteresis-heating alternating field is the most widely used magnetic field. 210 When MNPS are exposed to alternating magnetic fields (AMFs), the heat is dissipated arising from thermodynamic irreversibility, making them suitable for mediating magneto-thermal stimulation. 213 Magneto-thermal stimulation through MNPs can activate thermosensitive ion channels, such as TRPV1 and anoctamin1, to induce ion exchange in neurons, thus modulating neural activity.…”

Photoactive Nanomaterials for Wireless Neural Biomimetics, Stimulation, and Regeneration

“…It is reported that the formation of the growth cone influenced by the calcium levels of cells via regulation of the secretion of netrin-1 and BDNF. For example, the axonal growth can be accelerated by TRPV1-mediated Ca 2+ influx and thus activating the protein kinase A pathway . Cell fate is decided by the key cellular processes related to signaling and gene expression.…”

“…For example, the axonal growth can be accelerated by TRPV1mediated Ca 2+ influx and thus activating the protein kinase A pathway. 97 Cell fate is decided by the key cellular processes related to signaling and gene expression. Biomaterial substrates provide a promising way to mimic the natural biological microenvironment to active the components cell membrane, modulate neural signals.…”