Optical coherence tomography of cell dynamics in three-dimensional tissue models

Three-dimensional cell-based tissue models have been increasingly useful in the fields of tissue engineering, drug discovery, and cell biology. While techniques for building these tissue models have been advanced, there have been increasing demands for imaging techniques that are capable of assessing complex dynamic three-dimensional cell behavior in real-time and at larger depths in highly-scattering scaffolds. Understanding these cell behaviors requires advanced imaging tools to progress from characterizing two-dimensional cell cultures to complex, highly-scattering, thick three-dimensional tissue constructs. Optical coherence tomography (OCT) is an emerging biomedical imaging technique that can perform cellular-resolution imaging in situ and in real-time. In this study, we demonstrate that it is possible to use OCT to evaluate dynamic cell behavior and function in a quantitative fashion in four dimensions (three-dimensional space plus time). We investigated and characterized in thick tissue models a variety of cell processes, such as chemotaxis migration, proliferation, de-adhesion, and cell-material interactions. This optical imaging technique was developed and utilized in order to gain new insights into how chemical and/or mechanical microenvironments influence cellular dynamics in multiple dimensions. With deep imaging penetration and increased spatial and temporal resolution in three-dimensional space, OCT will be a useful tool for improving our understanding of complex biological interactions at the cellular level.