fabrication-magnetic-platforms-for-micron-scale-organization

Fabrication of Magnetic Platforms for Micron-Scale Organization of Interconnected Neurons

The ability to direct neurons into organized neural networks has great implications for regenerative medicine, tissue engineering, and bio-interfacing. ...

Bar Ilan University

Bar-Ilan University

The ability to direct and manipulate neuronal cells has important potential in therapeutics and neural network studies. An emerging approach for remotely guiding cells is by incorporating magnetic nanoparticles (MNPs) into cells and transferring the cells into magnetic sensitive units. Recent developments offer exciting possibilities of magnetic manipulations of MNPs-loaded cells by external magnetic fields. In the present study, we evaluated and characterized uptake properties for optimal loading of cells by MNPs. We examined the interactions between MNPs of different cores and coatings, with primary neurons and neuron-like cells.

Iron oxide nanoparticles for neuronal cell applications: uptake study and magnetic manipulations.

Nerve growth strongly relies on multiple chemical and physical signals throughout development and regeneration. Currently, a cure for injured neuronal tissue is an unmet need. Recent advances in fabrication technologies and materials led to the development of synthetic interfaces for neurons. Such engineered platforms that come in 2D and 3D forms can mimic the native extracellular environment and create a deeper understanding of neuronal growth mechanisms, and ultimately advance the development of potential therapies for neuronal regeneration. This progress report aims to present a comprehensive discussion of this field, focusing on physical feature design and fabrication with additional information about considerations of chemical modifications. We review studies of platforms generated with a range of topographies, from micro-scale features down to topographical elements at the nanoscale that demonstrate effective interactions with neuronal cells. Fabrication methods are discussed as well as their biological outcomes. This report highlights the interplay between neuronal systems and the important roles played by topography on neuronal differentiation, outgrowth, and development. The influence of substrate structures on different neuronal cells and parameters including cell fate, outgrowth, intracellular remodeling, gene expression and activity is discussed. Matching these effects to specific needs may lead to the emergence of clinical solutions for patients suffering from neuronal injuries or brain-machine interface (BMI) applications.

Interactions of Neurons with Physical Environments.

In this work, we describe a low-cost, two-step synthesis of composites of nitrogen-doped carbon quantum dots (NCDs) with γ-FeO (NCDs/γ-FeO), which is based on a hydrothermal cum co-precipitation method. The product is a fine powder of particles having an average diameter of 9 ± 3 nm. The physical and chemical properties of NCDs/γ-FeO were studied, as well as the superconducting quantum interference device and Mossbauer analysis of the magnetic properties of these nanocomposites. The interaction of NCDs/γ-FeO nanocomposites with neuron-like cells was examined, showing efficient uptake and low toxicity. Our research demonstrates the use of the nanocomposites for imaging and for controlling the cellular motility. The NCDs/γ-FeO nanocomposites are promising because of their biocompatibility, photostability, and potential selective affinity, paving the way for multifunctional biomedical applications.

Ultrafine Highly Magnetic Fluorescent γ-FeO/NCD Nanocomposites for Neuronal Manipulations.

Growth factors play an important role in nerve regeneration and repair. An attractive drug delivery strategy, termed "magnetic targeting", aims to enhance therapeutic efficiency by directing magnetic drug carriers specifically to selected cell populations that are suitable for the nervous tissues. Here, we covalently conjugated nerve growth factor to iron oxide nanoparticles (NGF-MNPs) and used controlled magnetic fields to deliver the NGF⁻MNP complexes to target sites. In order to actuate the magnetic fields a modular magnetic device was designed and fabricated. PC12 cells that were plated homogenously in culture were differentiated selectively only in targeted sites out of the entire dish, restricted to areas above the magnetic "hot spots". To examine the ability to guide the NGF-MNPs towards specific targets in vivo, we examined two model systems. First, we injected and directed magnetic carriers within the sciatic nerve. Second, we injected the MNPs intravenously and showed a significant accumulation of MNPs in mouse retina while using an external magnet that was placed next to one of the eyes. We propose a novel approach to deliver drugs selectively to injured sites, thus, to promote an effective repair with minimal systemic side effects, overcoming current challenges in regenerative therapeutics.

Article	Year
Iron oxide nanoparticles for neuronal cell applications: uptake study and magnetic manipulations. Journal of nanobiotechnology\| PubMed ID: 27179923	2016
Interactions of Neurons with Physical Environments. Advanced healthcare materials\| PubMed ID: 28640544	2017
Ultrafine Highly Magnetic Fluorescent γ-FeO/NCD Nanocomposites for Neuronal Manipulations. ACS omega\| PubMed ID: 30023817	2018
Magnetic Targeting of Growth Factors Using Iron Oxide Nanoparticles. Nanomaterials (Basel, Switzerland)\| PubMed ID: 30201889	2018

Michal Marcus

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