Cell culture in stacked, paper-supported gels offer a uniquely flexible approach to study cell responses to 3D molecular gradients, and to mimic tissue- and organ-level functions.
Permeating a suspension of cells in hydrogels into the sheets of chromatography paper creates thin 3D tissues in which the growth of cells is not limited by mass transport of oxygen or nutrients. Stacking and de-stacking layers of paper impregnated with suspensions of cells in extracellular matrix hydrogel make it possible to control oxygen and nutrient gradients in 3D, and to analyze molecular and genetic responses. Stacking assembles the "tissue," whereas de-stacking disassembles it, and permits its analysis.
Using these systems, we study the role of molecular gradients on drug and radiation sensitivity of cancer cells in 3D tumors, mineralization in 3D bone-like constructs, and the formation of 3D bacterial communities (biofilms). We project that paper, which is widely available in any laboratory, and simple to use, will become the foundation for the next generation screening and bioassay platforms that use 3D tissues as assay targets.