Others demonstrated that the topography and chemical composition of unmodified fibers affect cell-scaffold interactions. (44) This work also showed that endothelial cells (HUVECs) readily attached to the fibers through a nonligand mediated process. Qin noted human-induced hepatocytes (hiHEPs) selectively formed spheroid-like aggregates in high fiber density regions of filter paper scaffolds. In addition to supporting cell-laden hydrogel slabs, the cellulose fibers can also support the cells directly. Unlike other 3D culture platforms, cells can be readily retrieved from the scaffolds without fixation, allowing for spatially resolved characterization or further culture. The scaffolds, which can be stacked to form thick structures composed of multiple cell types or extracellular matrixes, are suitable for prolonged culture periods and are compatible with many standard cell-based analyses. The patterning and chemical modification strategies developed for paper-based microfluidics are translatable, generating defined cell culture regions or enhancing cellular attachment to the cellulose fibers. In Tissue Papers, cells or cell-laden hydrogels are seeded directly into paper-based scaffolds with readily available lab equipment (e.g., a micropipette). We refer to these cultures as Tissue Papers, an appropriate name as the setups use materials from (plant) tissue to generate functional (human) tissue structures. Paper-based cultures hold the potential to revolutionize the preparation and analysis of tissue-like structures. Copyright 2016 American Chemical Society. Part E was reproduced with permission from ref (97). The orange areas (left) contain the cellular culture chambers in paper. (D) Three-layer PDMS/paper hybrid microfluidic device used for uropathogen testing. Parts B and C were adapted with permission from ref (30).
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(C) A liver-on-a-chip device that uses a series of microfabricated posts to mimic the endothelial barrier in the liver sinusoid, separating hepatocytes from a surrounding flow channel. (B) Schematic of a lung-on-a-chip model containing a coculture of human alveolar epithelial cells and pulmonary capillary endothelial cells on the opposite sides of a membrane (left), image of the assembled device (top right), and scanning electron micrograph of the device before assembly (bottom right). Part A was reproduced with permission from ref (12). (A) Compilation of images displaying the gradients of proliferation, viability, oxygen, and nutrients that form across spheroids. You can also share passwords securely with family and friends over a data-encrypted channel.Figure 1.
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