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.
摘要:
机械性创伤导致的脑损伤是一个持续存在的全球公共卫生问题。继续开发几种外伤性脑损伤(TBI)的体外和体内模型,以描绘其发作和进展中涉及的各种复杂的病理生理过程。开发基于皮质球体的体外TBI模型目前尤其令人感兴趣,因为它们可以复制体内脑组织的关键方面,包括它的电生理学,物理化学微环境,和细胞外基质组成。能够使球体机械变形是任何有效的体外TBI模型中的关键要求。球体的形状和大小,然而,使它们机械加载,特别是在高通量中,无菌,和可重复的方式,相当具有挑战性。为了应对这一挑战,我们提出了一个基于球体的想法,体外TBI模型,其中球状体通过离心机旋转而机械加载。(这个新想法的实验演示将很快在其他地方发表。)可以限制其效用和范围的一个问题是,2D和3D体外TBI模型中使用的成像技术不能轻易地应用于其中以确定球体应变。为了解决这个问题,我们开发了一种基于连续介质力学的理论来估计球体以恒定角速度旋转时的应变。力学理论,虽然适用于基于离心机的TBI模型的特殊情况,也具有一般价值,因为它可以帮助TBI模型的进一步探索和发展。