Directional control of neurite outgrowth: emerging technologies for Parkinson's disease using magnetic nanoparticles and magnetic field gradients.

A challenge in current stem cell therapies for Parkinson's disease (PD) is controlling neuronal outgrowth from the substantia nigra towards the targeted area where connectivity is required in the striatum. Here we present progress towards controlling directional neurite extensions through the application of iron-oxide magnetic nanoparticles (MNPs) labelled neuronal cells combined with a magnetic array generating large spatially variant field gradients (greater than 20 T m-1). We investigated the viability of this approach in both two-dimensional and organotypic brain slice models and validated the observed changes in neurite directionality using mathematical models. Results showed that MNP-labelled cells exhibited a shift in directional neurite outgrowth when cultured in a magnetic field gradient, which broadly agreed with mathematical modelling of the magnetic force gradients and predicted MNP force direction. We translated our approach to an ex vivo rat brain slice where we observed directional neurite outgrowth of transplanted MNP-labelled cells from the substantia nigra towards the striatum. The improved directionality highlights the viability of this approach as a remote-control methodology for the control and manipulation of cellular growth for regenerative medicine applications. This study presents a new tool to overcome challenges faced in the development of new therapies for PD.

Quantifying the computational capability of a nanomagnetic reservoir computing platform with emergent magnetisation dynamics.

Devices based on arrays of interconnected magnetic nano-rings with emergent magnetization dynamics have recently been proposed for use in reservoir computing applications, but for them to be computationally useful it must be possible to optimise their dynamical responses. Here, we use a phenomenological model to demonstrate that such reservoirs can be optimised for classification tasks by tuning hyperparameters that control the scaling and input-rate of data into the system using rotating magnetic fields. We use task-independent metrics to assess the rings' computational capabilities at each set of these hyperparameters and show how these metrics correlate directly to performance in spoken and written digit recognition tasks. We then show that these metrics, and performance in tasks, can be further improved by expanding the reservoir's output to include multiple, concurrent measures of the ring arrays' magnetic states.

Magnetic Nanoparticle-Mediated Orientation of Collagen Hydrogels for Engineering of Tendon-Mimetic Constructs.

Despite the high incidence of tendon injuries worldwide, an optimal treatment strategy has yet to be defined. A key challenge for tendon repair is the alignment of the repaired matrix into orientations which provide maximal mechanical strength. Using oriented implants for tissue growth combined with either exogenous or endogenous stem cells may provide a solution. Previous research has shown how oriented fiber-like structures within 3D scaffolds can provide a framework for organized extracellular matrix deposition. In this article, we present our data on the remote magnetic alignment of collagen hydrogels which facilitates long-term collagen orientation. Magnetic nanoparticles (MNPs) at varying concentrations can be contained within collagen hydrogels. Our data show how, in response to the magnetic field lines, MNPs align and form string-like structures orientating at 90 degrees from the applied magnetic field from our device. This can be visualized by light and fluorescence microscopy, and it persists for 21 days post-application of the magnetic field. Confocal microscopy demonstrates the anisotropic macroscale structure of MNP-laden collagen gels subjected to a magnetic field, compared to gels without MNP dosing. Matrix fibrillation was compared between non- and biofunctionalized MNP hydrogels, and different gels dosed with varying MNP concentrations. Human adipose stem cells (hASCs) seeded within the magnetically aligned gels were observed to align in parallel to MNP and collagen orientation 7 days post-application of the magnetic field. hASCs seeded in isotropic gels were randomly organized. Tenocyte-likeness of the cells 7 days post-seeding in collagen I scaffolds was confirmed by the positive expression of tenomodulin and scleraxis proteins. To summarize, we have developed a convenient, non-invasive protocol to control the collagen I hydrogel architecture. Through the presence or absence of MNP dosing and a magnetic field, collagen can be remotely aligned or randomly organized, respectively, in situ. Tendon-like cells were observed to organize in parallel to unidirectionally aligned collagen fibers and polydirectionally in non-aligned collagen constructs. In this way, we were able to engineer the constructs emulating a physiologically and pathologically relevant tendon niche. This can be considered as an innovative approach particularly useful in tissue engineering or organ-on-a-chip applications for remotely controlling collagen matrix organization to recapitulate the native tendon.

Suppression of Stochastic Domain Wall Pinning Through Control of Gilbert Damping.

Finite temperature micromagnetic simulations were used to investigate the magnetisation structure, propagation dynamics and stochastic pinning of domain walls in rare earth-doped Ni80Fe20 nanowires. We first show how the increase of the Gilbert damping, caused by the inclusion rare-earth dopants such as holmium, acts to suppress Walker breakdown phenomena. This allows domain walls to maintain consistent magnetisation structures during propagation. We then employ finite temperature simulations to probe how this affects the stochastic pinning of domain walls at notch-shaped artificial defect sites. Our results indicate that the addition of even a few percent of holmium allows domain walls to pin with consistent and well-defined magnetisation configurations, thus suppressing dynamically-induced stochastic pinning/depinning phenomena. Together, these results demonstrate a powerful, materials science-based solution to the problems of stochastic domain wall pinning in soft ferromagnetic nanowires.