Nanocomposite Hydrogel Bioinks for 3D Printing of Living Cells

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3D printing of living cells, or 3D bioprinting, holds great promise to build 3D tissues and, ultimately, organs. However, despite recent advances in 3D printing of non-biological materials, 3D printing of living cells remains a challenge. One of the key challenges is the lack of bioinks with 3D printability and biocompatibility. This award supports fundamental research on nanocomposite hydrogel bioinks that encapsulate living cells in 3D printing process. Results from this research will enable not only the rational design of cell-encapsulating bioinks with 3D printability and biocompatibility, but also the high resolution 3D printing of tissue structures. This research potentially benefits many areas in biomedicine, including the development of tissue and organ models, tissue engineering, and regenerative medicine.The research objectives of this project are (1) to understand the effects of compositions of cell-laden nanocomposite bioinks on their dynamic mechanical properties (shear-thinning and self-healing properties) and cell viability; and (2) to establish the relationship between the dynamic mechanical properties of cell-laden nanocomposite bioinks and their 3D printability and cell-compatibility (cell viability in printed tissues). To achieve the first objective, gel-phase nanocomposite bioinks that consist of surface-functionalized single-walled carbon nanotubes, gelatin methacrylate (hydrogel matrix), and living cells will be synthesized. The concentration of nanotubes and gelatin methacrylate will be varied from 0 to 10% with the total solid fraction of less than 10%. Fibroblasts and mesenchymal stem cells (10^6 to 10^8 cells/mL) will be used as model cells. The storage and loss shear moduli of these gel-phase bioinks will be measured with oscillatory strain sweeps and strain steps (thixotropy) using a rheometer to determine the shear-thinning and self-healing properties. The viability of cells encapsulated in bioinks will be measured (hourly and daily up to 7 days). To achieve the second objective, multilayer 3D tissue structures will be printed with 100 and 200 micron nozzles. The 3D printability of gel-phase bioinks will be determined by characterizing printed structures (shape definition and structural integrity) using optical microscopy. Bioinks that produce self-supporting 3D structures with a filament diameter of less than 200 microns will be defined as 3D printable. The cell-compatibility of nanocomposite bioinks will be determined by measuring the viability of cells in printed tissues (daily up to 7 days).