UCLA

Objective: Three dimensional cell and tissue culture outcomes depend on mechanical forcesin their environment and sufficient delivery of nutrients and removal of waste. Flow and shear influence parenchymal cell distribution and vascular morphogenesis. Herein a bioreactor which can control fluid flow and shear patterns over large areas was developed as a tool for tissue engineering. Methods: A 12-inlet perfusion bioreactor was constructed to be compatible with multiple types of tissue engineering scaffolds including biopolymer hydrogels and macroporous sponges and can support the growth and viability of thick tissue scaffolds. Scaffolds containing mammalian cells cultured under flow were compared to static conditions and other flow patterns. Results: Flow patterns in the scaffolds were obtained using MRI flow maps. Hydrogels and commercial sponges were assessed for 3D culture compatibility and Gel 2 (a specific ECM hydrogel mixture), Collagen, and Gelatin sponges were found to be both optimal for cell growth and compatible with perfusion flow. Culture experiments determined the feasibility of our bioreactor in supporting thick tissue growth and viability and various flow patterns were shown to alter cell distribution, growth, and viability. Conclusion: We demonstrated the ability of the bioreactor to implement macroscopic, tunable flow patterns in a biocompatible environment suitable for cell and tissue culture and found distinct differences in tissue development from different flow patterns. Significance: The bioreactor will enable future studies on different flow patterns and their effects on cell growth and viability for medically relevant tissues and could inform on culture conditions that better mimic what occurs in vivo during tissue development.