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

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. In this study, we demonstrate that it is possible to use OCT to non-destructively evaluate dynamic cell behavior and function in a quantitative fashion in four dimensions (3-D space plus time). Dynamic processes including cell migration, proliferation, apoptosis, necrosis, and mechanical restructuring are observed during engineering tissue development. 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.