| Bottom-up tissue engineering pursues automated process control over human tissue fabrication using the fundamental cellular, soluble, and architectural components as the working material. Key technology for methodological progress of bottom-up tissue engineering includes advanced biofabrication techniques to assemble viable biological material in 3-dimensional space and microfluidic devices to control timing and sequence of environmental stimulation. The presented research's objective is the development of design, characterization and fabrication approaches which integrate physiologically relevant microfluidic techniques and hetero-cellular architecture for cell-laden models by leveraging combinations of the biofabrication techniques; including precision extrusion deposition, multi-nozzle cell printing, replica molding, and a novel synchronized multi-material bioprinting system. This research focuses on the development of a synchronized multi-material bioprinter for the fabrication of 3D hetero-cellular models. The specific research objectives are: (1) combine multi-nozzle deposition system with a microlfuidic platform for controlled cell seeding in a microfluidic device for a hetero-cellular in vitro model for drug testing, (2) to define a 3D printing and replica molding processes to fabricate microfluidic and scaffold environments with control of the macro-scale (10-3-10-1 m) patterning of channels/structural elements and micro-scale (10-4-10 -3 m) channel cross-section of internal features, (3) to develop and characterize an integrated synchronized multi-material bioprinter system to produce nano-liter droplets and 10-4-10-3 m diameter filaments with a heterogeneous packaging resolution of 10 -5-10-3 m, and (4) to apply the synchronized multi-material bioprinter system to produce hetero-cellular models to study radioprotective drug efficacy in co-culture and metabolism rates in simulated weightlessness environments. The presented biofabrication methods are applied to fabricate a hetero-cellular liver model to study drug efficacy of the pro-drug amifostine to shield liver from radiation genetic damage and pharmacokinetic up-take in model microgravity. |
