Unveiling Multidimensional Physicochemical Design Principles for Tissue Processing Hydrogels

Abstract A thorough understanding of living systems necessitates detailed mapping of the high‐dimensional molecular landscapes within intact, thick biological tissues. Recent advances in hydrogel‐based tissue processing and clearing techniques have facilitated 3D visualization of biological systems while preserving their native spatial context. Although various polymer hydrogels have been developed for tissue processing, systematic elucidation of their workflow‐dependent properties from a materials science perspective remains lacking, hindering the establishment of design principles for multifunctional performance. Here, a physicochemical design framework for polymer hydrogels in tissue processing is presented, derived from a comprehensive analysis of materials employed in four representative platforms. This analysis encompasses chemo‐rheological parameters, swelling behavior, micro/nano…