5D Electro-Mechanical Bio-Interface for Neuronal Tissue Engineering

Introduction

The cellular microenvironment is tightly regulated by biochemical and physical cues. While state-of-the-art electrical and mechanical devices can perturb the biophysical cell niche in 2D monolayers, 3D tissue cultures are considered a much more comprehensive and representative model of the in vivo microenvironment.

Limitations of Current Technologies

However, the available biomodulation “toolkit” does not meet the required level of complexity, specificity, and accuracy. This limitation hinders the ability to address basic questions in brain research and to develop new nonpharmacological interventions such as next-generation neuroengineering technologies and biointerfaces.

Proposed Solution

We propose to develop a novel biomaterial for nongenetic leadless electrical and mechanical biomodulation in 3D engineered tissues.

Electrical Biomodulation

The leadless electrical biomodulation will be induced via optical illumination of semiconducting silicon micro- and nanostructures, which will potentially yield spatial resolution of hundreds of nanometers, two orders of magnitude smaller than the current state-of-the-art 3D biointerfaces.

Mechanical Perturbation

The mechanical perturbation will be achieved by spatially defined iron microstructures that will be manipulated via spatially homogenous magnetic fields, resulting in mechanical perturbation resolution down to a few microns, which is unprecedented in 3D tissue constructs.

Integration of Technologies

Lastly, we will integrate the two materials into a single 3D platform to construct the 5D-NEURO, allowing leadless electrical and mechanical bi-modal perturbation simultaneously and independently.

Objectives

Herein, we will both establish a new tool for biophysical modulation and generate new fundamental knowledge about the role of bioelectrical, biomechanical, and their synergistic effect on neuronal growth and regeneration in 3D models.

Future Applications

Moreover, such a platform lays the ground for next-generation engineered tissues for applications spanning from fundamental brain developmental research to future translational clinical interventions.