4D bioprinting is a highly innovative additive manufacturing process to fabricate pre-designed, self-assembly structures with the ability to change their shape over time. However, current 4D bioprinting based additive manufacturing technologies are hindered by the lack of advanced smart "inks", low cell viability, and poor modulation of cellular function within manufactured tissue constructs. This EArly-concept Grant for Exploratory Research (EAGER) award supports fundamental research to address these obstacles in 4D bioprinting. The research aims to create smart bioinks with shape memory behavior and 4D bioprint complex tissue constructs. Research results can help bring 4D bioprinting to the forefront of biomedicine as a useful rapid prototyping tool. This can potentially benefit numerous patients with various tissue defects.
The research objectives of this project are (1) to establish the relationship between printing parameters (laser power, printing speed, and printing distance) and the shape memory effect of 4D bioprinted complex tissue constructs, and (2) to understand the effects of 4D dynamic shape change on neural stem cell viability, growth, and differentiation. To achieve the first objective, a novel smart lipid macromer with highly reactive printable groups and functional segments will be synthesized and 4D bioprinted into smart constructs. Three printing parameters will be varied as follows: laser power from 5000 to 10000 Hz, printing speed from 1000 to 3000 mm/min, and printing distance from 1 to 3 mm. The microstructure of the bioprinted constructs will be observed via scanning electron microscopy, the tensile strength of the constructs will be measured using a uniaxial mechanical tester, and the shape memory effects of the constructs will be determined with shape memory tests. To achieve the second objective, the bioprinted constructs will be fixed at a temporary shape and restore their original shape with varied recovery process and recovery speed. Neural stem cell viability in the 4D bioprinted constructs will be quantified using a live/dead viability assay; neural stem cell growth, axonal extension, and differentiation will be measured via a cell proliferation assay and immunocytochemistry staining.
