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

Abstract

Brain injuries resulting from mechanical trauma represent an ongoing global public health issue. Several in vitro and 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 in vitro TBI model that is based on cortical spheroids is especially of great interest currently because they can replicate key aspects of in vivo brain tissue, including its electrophysiology, physicochemical microenvironment, and extracellular matrix composition. Being able to mechanically deform the spheroids are a key requirement in any effective 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, 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 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.