Nano-Based Platforms Combined with Growth Factors for Promoting Neuronal Differentiation and Growth

The ability to manipulate and direct neuronal growth has great importance in the field of tissue engineering, both for neuronal repair and potential medical devices. Following nerve injury, such as peripheral or central nerve injury, and neurodegenerative diseases, spontaneous nerve regeneration is often partial and limited, arising the need to develop technologies for optimal regrowth conditions. Neuronal growth, directionality, effective elongation, and level of connectivity play key roles in recapitulating functional capabilities. In this talk I will present our recent studies of 3D nanostructured platforms and magnetic-based manipulations for promoting and directing neuronal growth and for controlling drug delivery. Techniques to control cell growth include bio-mimetic scaffolds, nano-fibrous constructs, gels and oriented gels, offering a mechanical guide to the regenerating axons. We have developed a novel approach of injectable hydrogels combined with magnetic nanoparticles (MNPs), to be incorporated directly into the injured site. We show that gel fiber structure can be aligned in situ dynamically and remotely in response to an external magnetic field. In addition, we functionalize the MNPs, for example by Nerve Growth Factor coating, presenting a ‘smart’ delivery system of biomolecules, together with integral guidance cues. We also use the magnetic nanoparticles (MNPs) as mediators to apply forces locally on neurons throughout their migration. Following incubation MNPs accumulated in the cells, turning the cells sensitive to magnetic stimulation. Applying magnetic fields with controlled magnetic flux densities at multiple scales has led to an organized network of cell clusters. With this method we control drug distribution and delivery as well. Our study presents an emerging magneto-chemical approach for promoting neuronal growth and repair.

Antman-Passig et al., Tissue Eng., 2017; Antman-Passig and Shefi, Nano Letters, 2016; Marcus et al., J NanoBioTech., 2016