ABSTRACT
Hydrophilic tissue clearing protocols represent one of the major categories of recently emerging optical tissue clearing methods. For over 20 years, researchers have tested many water-soluble compounds for tissue clearing purposes. The primary role of the previously found tissue clearing compounds was expected to match the tissue and reagents' optical properties to suppress internal light scattering. However, some of the recent hydrophilic tissue clearing protocols utilize additional compounds with powerful delipidation, decalcification, decolorization, and swelling functions to achieve more efficient clearing results. Large-scale profiling of water-soluble chemicals has characterized their chemical structures and the properties that were required for each step of tissue clearing. The high safety, biocompatibility, and simplicity of the hydrophilic tissue clearing protocol has contributed to the realization of a wide range of biomedical applications. In particular, 3D histopathology and whole-body or whole-organ profiling of cells will provide next-generation technologies for biomedical research and clinical practice. This chapter discusses 1) detailed chemical structures and properties for hydrophilic tissue clearing compounds, and 2) the potential of modern hydrophilic tissue clearing methods in biomedical research and clinical practice.
