A mechanics theory for the exploration of a high-throughput, sterile 3D $\textit{in vitro}$ traumatic brain injury model

TL;DR

This paper introduces a continuum mechanics theory to estimate strains in spheroids during centrifuge-based in vitro traumatic brain injury modeling, enabling high-throughput, sterile, and reproducible mechanical loading of brain tissue models.

Contribution

It presents a novel mechanics theory for spheroid deformation estimation during centrifuge-based TBI modeling, facilitating better design and analysis of in vitro brain injury experiments.

Findings

Developed a continuum mechanics model for spheroid strain estimation

Applicable to centrifuge-based TBI models and general tissue deformation analysis

Supports high-throughput, sterile, and reproducible in vitro TBI experiments.

Abstract

Brain injuries resulting from mechanical trauma represent an ongoing global public health issue. Several $\textit{in vitro}$ and $\textit{in vivo}$ models for traumatic brain injury (TBI) continue to be developed for delineating the various complex pathophysiological processes involved in its onset and progression. Developing an $\textit{in vitro}$ TBI model that is based on cortical spheroids is especially of great interest currently because they can replicate key aspects of $\textit{in vivo}$ brain tissue, including its electrophysiology, physicochemical microenvironment, and extracellular matrix composition. Being able to mechanically deform the spheroids is a key requirement in any effective $\textit{in vitro}$ TBI model. The spheroids' shape and size, however, make mechanically loading them, especially in a high-throughput, sterile, and reproducible manner, quite challenging. To address this challenge, we present an idea for a spheroid-based, $\textit{in vitro}$ TBI model in which the spheroids are mechanically loaded by being spun by a centrifuge. (An experimental demonstration of this new idea will be published shortly elsewhere.) An issue that can limit its utility and scope is that imaging techniques used in 2D and 3D $\textit{in vitro}$ TBI models cannot be readily applied in it to determine spheroid strains. In order to address this issue, we developed a continuum mechanics-based theory to estimate the spheroids' strains when they are being spun at a constant angular velocity. The mechanics theory, while applicable here to a special case of the centrifuge-based TBI model, is also of general value since it can help with the further exploration and development of TBI models.