Transparent Porous Polysaccharide Cryogels Provide Biochemically Defined, Biomimetic Matrices for Tunable 3D Cell Culture

Biomimetic scaffolds are desirable for 3D cell culture, yet optically transparent, macroporous, polysaccharide hydrogels have been limited. By incorporating soluble mono- and disaccharide additives during cryogelation, we synthesized biomimetic scaffolds and gained insight into the mechanism of their formation. The mono/disaccharide additives affect the size of ice crystal porogens and interact with polysaccharide polymers, altering cryogel pore size and mechanical properties. Importantly, gel transparency is maintained following removal of additives, enabling their use as biomimetic extracellular matrices. We demonstrate both optical transparency with 3D spatial control of immobilized bioactive growth factors using multiphoton patterning and cellular response to immobilized ligands.