(334a) Paper-Based Cell Culture Platforms for Personalized Medicine

Two-dimensional (2D) cell culture platforms do not recapitulate the events that occur within the native microenvironment of tissues. Current tissue engineering models utilize sophisticated instrumentation or expensive set-ups for fabrication of three-dimensional (3D) scaffolds, require extensive optimization procedures, and do not provide physiologically relevant size structures in centimeter-scale. The resulting constructs usually contain heterogeneously distributed cells and demonstrate mass transport limitations. It is, therefore, challenging to fabricate biocompatible constructs for personalized medicine. In this work, we developed paper-based cell culture platforms for a wide range of applications that involve mammalian cells, bacteria, fungi, and plants cells. These new cell culture platforms are flexible, tunable, simple, low-cost, and amenable to high-throughput sample preparation and analysis.

We used paper-based scaffolds as matrices to support cells and hydrogels in 3D. We have grown various types of cells (e.g. stem cells, primary cells from animals and humans, cells from patient biopsies, immune cells, fibroblasts, osteoblasts, epithelial cells, tumor cells, bacteria, fungi, or plant cells) in paper scaffolds. After the desired cell culture period, we monitored and characterized the behavior of cells through standard analytical assays such as cytotoxicity, metabolic activity, proliferation, DNA content, protein content, apoptosis, immunostaining, high-resolution imaging, and mechanical tests.

We fabricated and utilized paper-based scaffolds for different applications in personalized medicine. For example, we investigated migration of primary human tumor cells (isolated from patients) in a multilayered paper-based cell culture platform. This approach can be adapted to screen different doses of chemotherapeutics or radiation in a patient-specific fashion. We also used paper scaffolds to induce template-guided biomineralization in origami-inspired structures. This method can be used to fabricate constructs for patients who have irregular size and shape bone defects. In addition, we generated wax-printed patterns in paper scaffolds that are for high-throughput sample preparation and analysis of osteoblast cultures. We have shown that we can easily form and control gradients of oxygen, nutrients, and other biological molecules in paper-based cell culture platforms. We also used these systems to culture bacteria, fungi, and plant cells and developed in vitrodisease models. Due to porous nature of paper, there is no mass transport limitations to the cells. Our results demonstrated that the paper scaffolds enable patterning from micron to cm scale, adapt modular configurations, can provide physiologically relevant tissue models, and cells can easily be recovered from these scaffolds for further analysis. Paper scaffolds can also be used for origami-inspired tissue engineering for a host of applications.

We recently developed new paper-based cell culture platforms to fabricate multicellular and compartmentalized tissue-mimetics for clinical applications. To overcome the major limitations of the traditional tissue models, we adapted a layer-by layer strategy to assemble tissue-like structures from low-cost and biocompatible paper-based materials. This approach offers unique opportunities from understanding fundamental biology to developing disease models for personalized medicine, and assembling different tissues for organ-on-paper configurations.