Bioengineered three-dimensional design to promote neuronal regeneration

Dr. Dekel Rosenfeld

Biomedical Engineering, Faculty of Engineering

We develop magnetic functional materials to interact with electrogenic cells for neuromodulation and control over peripheral organ function. These tools allow remote control on calcium-dependent processes via activation of ion channels such as heat sensitive ion channels. It provides spatial and temporal resolution in a minimally invasive procedure demonstrated both in vitro and in vivo. We developed a novel approach to control the release of adrenal stress hormones to treat hormonal imbalance in mental health disorders such as post trauma stress disorder.

Our ultimate goals are developing new tools that advance the biomedical research to repair organ dysfunction and studying the organ-brain communication in health and disease.

Nerve injuries are common and full recovery is challenging. The available therapeutic
interventions mostly rely on surgical procedures, which cannot guarantee complete regeneration
of the injured nerve and sufficient restoration of function. Among other factors, 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 the current
limitations and augment available treatments of nerve injury. Moreover, combining the available
methods with new mechanisms that can accelerate axonal growth at the injury site, can lead to
the desired breakthrough in this field.
This project will focus on discovery of a novel mechanism that can accelerate axonal growth via
calcium signaling and by activation of the heat sensitive and calcium permeable ion channel,
TRPV1. We rely on the magnetothermal approach in which magnetic nanoparticles (MNPs)
dissipate heat upon exposure to alternating magnetic fields (AMFs) with high frequencies and
low amplitudes (~10s mT). By creating scaffolds bearing MNPs and dissipating heat under
alternating magnetic fields, we will examine the role of Schwann cellsin TRPV1-depedednt axonal
growth within a co-culture model. We will employ those results to our previously established
model of dorsal root ganglion explant, where accelerated axonal elongation was observed under
magnentothermal stimulation.
We envision, that wireless magnetothermal control of calcium influx will advance understanding
of calcium-dependent pathways involved in axonal growth, while offering a minimally invasive
strategy to enhance nerve regeneration following injury using three-dimensional implants or
combined with other intervention methods.