Optical coherence tomography of cell dynamics in three-dimensional engineered tissues

Abstract

Cell-based engineered tissue models have been increasingly useful in the field of tissue engineering, in in vitro drug screening systems, and in complex cell biology studies. While techniques for engineering tissue models have advanced, there have been few imaging technique capable of assessing the complex 3-D cell behaviors in real-time and at the depths that comprise thick tissues. Understanding cell behavior requires advanced imaging tools to progress from characterizing 2-D cell cultures to complex, highly-scattering, thick 3-D tissue constructs. Optical coherence tomography (OCT) is an emerging biomedical imaging technique that can perform cellular-resolution imaging in situ and in real-time. OCT, which uses near-infrared laser light, provides deep-tissue imaging up to several millimeters within highly-scattering tissue, thus permitting visualization of changes at depths previously unattainable. 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 (3-D space plus time). We investigated and characterized cell dynamics and processes in deep tissue models, such as cell de-adhesion, cell proliferation, cell chemotaxis migration, cell necrosis, and cell apoptosis. This optical imaging technique was developed and utilized in order to gain new insights into how chemical microenvironments influence cellular functions and dynamics in multi-dimensional models. In addition, by detecting the changes in cell dynamics, effective chemical concentration could be estimated. With high penetration depth and increased spatial and temporal resolution in 3-D space, OCT will be a useful tool for improving our understanding of cell dynamics in situ and in real-time, for elucidating the complex biological interactions, and for directing our designs toward functional and biomimetic engineered tissues.