# Plant‐Derived Viral Nanoparticles Enable Simultaneous Guidance of Neuronal Cell Outgrowth and Targeting of Neurodifferentiation Pathways

## TL;DR

This paper introduces a new method using plant-based nanoparticles to guide neuron growth and promote differentiation in a controlled way.

## Contribution

A novel approach using genetically engineered plant-derived viral nanoparticles to simultaneously guide neuronal growth and target differentiation pathways.

## Key findings

- VNPs displaying functional peptides enhance neuronal differentiation and neurite outgrowth.
- 3D alignment of VNPs creates a microarchitecture that guides directional cell growth.
- Genetic engineering of VNPs provides precise control over neural cell behavior.

## Abstract

Differentiating neuronal cells in vitro is a complex process that can be significantly enhanced by using a combination of functional peptides and nanostructured scaffolds in combination. However, applying these elements simultaneously remains challenging. Here, a novel neural tissue engineering approach that uses plant‐derived viral nanoparticles (VNPs) to simultaneously promote neuronal differentiation and growth guidance is presented. It is hypothesized that the simultaneous alignment and promotion of neurodifferentiation could be achieved by using genetically engineered potato virus X and tobacco mosaic virus, which display high local concentrations of functional peptides derived from laminin (RGD and IKVAV) and brain‐derived neurotrophic factor. Immunostaining, gene analysis, immunoprecipitation, and western blotting are employed to evaluate the effect of VNPs on neurodifferentiation and their mechanism of action via cell membrane receptors. 3D printing with sacrificial materials is used to align the VNPs, as confirmed by scanning electron microscopy. This approach creates an orientated microarchitecture that simultaneously combines growth guidance and pathway targeting. The incorporation of growth‐factor‐like peptides onto the VNP surface through genetic engineering represents a significant advancement in this area of research. This provides unparalleled control over neural cell differentiation and neurite outgrowth by utilizing plant‐derived, bioactive, and biomimetic nanoparticles as a multifunctional scaffold base.

A neuronal tissue engineering approach employing plant‐derived viral nanoparticles (VNPs) that have been genetically engineered to display functional peptides is presented. These VNPs simultaneously promote neuronal differentiation and directional growth. Aligning VNPs creates a defined microarchitecture that guides neurite extension and enhances the differentiation of neural precursor cells.