Expanding sacrificially printed microfluidic channel-embedded paper devices for construction of volumetric tissue models in vitro.

We report a method for expanding microchannel-embedded paper devices using a precisely controlled gas-foaming technique for the generation of volumetric tissue models in vitro. We successfully fabricated hollow, perfusable microchannel patterns contained in a densely entangled network of bacterial cellulose nanofibrils using matrix-assisted sacrificial three-dimensional printing, and demonstrated the maintenance of their structural integrity after gas-foaming-enabled expansion in an aqueous solution of NaBH4. The resulting expanded microchannel-embedded paper devices showed multilayered laminar structures with controllable thicknesses as a function of both NaBH4 concentration and expansion time. With expansion, the thickness and porosity of the bacterial cellulose network were significantly increased. As such, cellular infiltration was promoted comparing to as-prepared, non-expanded devices. This simple technique enables the generation of truly volumetric, cost-effective human-based tissue models, such as vascularized tumor models, for potential applications in preclinical drug screening and personalized therapeutic selection.