Abstract

3D Bioprinting Personalized Neural Tissues

Stephanie Willerth, Associate Professor and Canada Research Chair in Biomedical Engineering, University of Victoria

Neurological drugs entering clinical trials fail over 90% of the time due to lack of efficacy or unforeseen toxicity. Better pre-clinical tools for predicting the effectiveness and toxicity of potential drug targets would significantly lower the chance of drug failure during clinical trials, reducing the cost of drug development and decreasing the healthcare burden of neurodegenerative diseases. Developing novel 3D multi-cellular neural tissue models that recapitulate the features of neurodegenerative diseases can serve as a convenient drug screening tool with increased physiological relevance. Human induced pluripotent stem cells (hiPSCs) serve as an important tool when engineering neural tissues as they can be expanded and differentiated into neurons. However, current methods for generating physiological neural tissue from human pluripotent stem cells are low throughput, inconsistent, and labor intensive. The Willerth lab produced 3D neural tissues derived from hiPSC-derived neural progenitors using the novel Lab-On-a-Printer (LOP)™ bioprinting technology (Aspect Biosystems). LOP™ technology enables rapid switching between different biomaterials during the production process, enabling multiple cell types and scaffold components to be precisely positioned in different regions within the same 3D tissue without changing the printhead. Alternative approaches to bioprinting such as ink-jet and needle extrusion, expose the cells to high levels of shear stress when they are forced out of the printhead. Higher print speeds and pressures, higher viscosities of bioink, or smaller gauge needles exacerbate these stresses. Human pluripotent stem cells, including hiPSCs, are fragile cells, particularly sensitive to high shear stress that may cause unexpected cell death and premature differentiation, thus the RX1 bioprinter is the ideal system as its printing process only exposes cells to low shear stresses during the printing process. It also prints these structures in a rapid fashion, taking minute to produce each structure – providing a distinct advantage in terms of throughput in comparison to traditional tissue engineering methods.