Abstract
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.
Highlights
Cell activities in three-dimensional (3-D) tissue models are of great interest for both basic cell biology research and applications, such as tissue engineering and pharmacological research [1,2]
Optical coherence tomography (OCT) has the potential for following these dynamic processes in the developing engineered tissue model, where artificial scaffolds play a central role for defining the early morphology of the tissue
We demonstrate that OCT, frequently used for generating histology-like images of tissue structure, can be used to track and analyze cell dynamics in tissue models
Summary
Cell activities in three-dimensional (3-D) tissue models are of great interest for both basic cell biology research and applications, such as tissue engineering and pharmacological research [1,2]. Newer technologies for imaging tissue models, including highfield-strength magnetic resonance imaging and microcomputed tomography, have been pursued for the assessment of cell and scaffold structure, with limited success. These techniques, with long data acquisition rates, hazards associated with high-energy radiation, and relatively high costs, are less suitable for both real-time and long-term imaging [8,9]. We investigate and characterize cell dynamics and processes including 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 microenvironments influence cellular functions and dynamics in multi-dimensional models. Compared to other microscopy approaches, OCT permits high-resolution, real-time, deep-tissue, 3-D imaging to be performed rapidly and repeatedly over extended periods of time with intact, living tissue models, with the potential to extend imaging of scaffolds to in vivo applications, such as following grafting of engineered tissues into a host tissue
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