Collagen-cell interactions in three-dimensional microenvironments

Scientists and engineers in academia and industry rely heavily on in vivo animal models and conventional two-dimensional (2D) cell culture for investigating various biological processes, chemical toxicity testing, as well as the discovery and development of next-generation drugs and medical therapies. While 2D culture platforms facilitate the study of molecular processes, these systems do not account for the complexity of biological signaling provided by the 3D extracellular microenvironment. This shortcoming has led to a substantial interest in the development of in vitro tissue systems that are human-cell based and recapitulate the complexities of 3D tissues, including the dynamic and spatiotemporal biochemical and physical signaling inherent to the in vivo microenvironment. This chapter discusses design considerations and approaches for development of 3D in vitro collagen-based tissue systems. In addition, an overview of state-of-the-art imaging tools and techniques for visualizing and quantifying multiscale cell-fluid-matrix interactions is provided.