Magnetic particles for nerve regeneration (MARVENE)
Nerve regeneration is a complex biological phenomenon. In the peripheral nervous system, nerves regenerate spontaneously only when injuries are minor. With severe nerve injuries, i.e., complete transections, surgical repair is necessary either by direct end-to-end approximation of the viable nerve ends with fine sutures or the use of an autologous nerve graft if the gap between the two ends is extensive. Disadvantages of autologous nerve graft include loss of function at the donor site and the need for complex and difficult operations with varying clinical outcomes.
Molecular and cell therapies have been explored as alternatives to surgical nerve grafting for the treatment of severe peripheral nerve injuries. However, to date there has been no progress of undoubted clinical benefit. The recent advances in nanoscience may provide new therapeutic possibilities as alternatives/supplements to established surgical techniques. Specifically, the MARVENE project is concerned with the use of magnetic nanoparticles (MNPs) as functional nano-objects to enhance the nerve regeneration and provide guidance for the regenerating axons. MNPs could open the frontiers for new therapies based on the exploitation of the mechanical forces acting on MNP bound to neurons to promote axonal elongation/growth. Furthermore, the realization of MNPs functionalised with neurotrophic factors offer distinct possibilities for novel molecular therapy and when bound to mesenchymal stem cells, MNPs may form the basis for more effective cell therapy.
MNPs have unique properties which make them useful for applications to the biomedical field. Nanoparticles can be manufactured in various controllable sizes ranging from a few nanometres to tens of nanometres, i.e., with dimensions smaller than those of a cell (10–100 µm) and comparable to those of a virus (20–450 nm) or single protein (5–50 nm) or a gene (2 nm wide and 10–100 nm long). In other words they can be designed to ‘get close’ to biological entities of interest. Current applications of MNPs includes (i) magnetic separation of labelled cells and other biological entities; (ii) therapeutic drug, gene and radionuclide delivery; (iii) radio frequency methods for the catabolism of tumours via hyperthermia; and (iv) contrast enhancement agents for magnetic resonance imaging applications.
We are exploiting novel application of MNPs to enhance nerve regeneration. It is commonly accepted that physical guidance of axons is a vital component of nerve repair and research has demonstrated that biochemical signals as well as physical guidance are critical for nerve regeneration. MNPs, thanks to their ability to interact with living cells, generate mechanical strength for the cells under external magnetic fields. Apart from using MNPs to create mechanical tension that stimulates the growth and elongation of axons, use of stem cells is also one of the most promising approaches in nerve regeneration. One possibility to achieve restoration of neuronal function is to provide an exogenous source of myelinating cells via transplantation. In this context, mesenchymal stem cells (MSCs) have attracted interest. Here, MNPs become useful to improve the localization, the homing, the adhesion and thus the survival at the transplantation site of the stem cells.