Magnetic Composite Biomaterials for Neural Regeneration

Abstract

Nervous system damage caused by physical trauma or degenerative diseases can result in loss of sensory and motor function for patients. Biomaterial interventions have shown promise in animal studies, providing contact guidance for extending neurites or sustained release of various drugs and growth factors; however, these approaches often target only one aspect of the regeneration process. More recent studies investigate hybrid approaches, creating complex materials that can reduce inflammation or provide neuroprotection in addition to stimulating growth and regeneration. Magnetic materials have shown promise in this field, as they can be manipulated non-invasively, are easily functionalized, and can be used to mechanically stimulate cells. By combining different types of biomaterials (hydrogels, nanoparticles, electrospun fibers) and incorporating magnetic elements, magnetic materials can provide multiple physical and chemical cues to promote regeneration. This review, for the first time, will provide an overview of design strategies for promoting regeneration after neural injury with magnetic biomaterials.

Keywords: biomaterials; iron oxide nanoparticles; magnetic nanoparticles; nervous system injury; neural regeneration.

Figure 1

Republished with permission of RSC Pub and the Royal Society of Chemistry from Amin et al. (2017) via Copyright Clearance Center. Schematic representation of the differential effects of the functionalized magnetic field on the transport of magnetic particles across the intact BBB in normal mice. The functionalized magnetic field was generated using an electromagnetic actuator, and a 10-min exposure time was used for each experiment. The magnetic particles successfully crossed the BBB and reached the brain under all observed functionalized magnetic field conditions. No histological changes or neurotoxicity in the brain was observed after the experiments. Moreover, BBB integrity was not disrupted by magnetic particle administration and the functionalized magnetic field.

Figure 2

MNP-mediated cell manipulation strategies. (A) MNPs are injected intravenously into the animal and an external magnet is used to localize the particles at the injury site. Local cells at the injury site internalize MNPs via endocytosis. MNPs elicit local mechanical forces in response to external magnetic field stimulation, inducing axonal extension or glial cell migration into the lesion. (B) Cells are cultured in vitro and labeled with MNPs. These cells are then injected into the animal and guided to the injury site with an external magnet. Once in the lesion (red area), cells can release regenerative factors to promote regeneration.

Figure 3

Republished with permission of RSC Pub and the Royal Society of Chemistry from Tukmachev et al. (2015) via Copyright Clearance Center. Magnetic system for MSC targeting into SCI. (A) In vivo application of the non-invasive magnetic system for MSC targeting into SCI of a rat. (B) Schematic representation of the magnetic targeting strategy.

Figure 4

Magnetic composite materials for supporting neural regeneration and non-invasive positioning. (A) MNPs embedded in a hydrogel can be aligned with a magnetic field and held in place as the gel solidifies. (B) MNP-loaded fibers can be aligned with a magnetic field and held in place as a gel solidifies. The MNPs can be functionalized with drugs, antibodies, nucleic acids, or fluorophores in either system. Naked MNPs can be loaded alongside drugs in the hydrogel or in the polymer fiber solution before electrospinning. Coaxial fibers with MNP-loaded core and drug-containing sheath can also be fabricated to offer magnetic alignment with tunable fiber nanotopography.