Design of a Hydrogel for 3-D Bioprinting Neural Tissue

Abstract

Neurodegenerative diseases and disorders affect millions of individuals in North America. The annual cost of treatment is in the billions and treatment options remain limited. Current methods focus on physical rehabilitation and drugs to mask declining neuron function. Drug therapies currently available can hide the effects of neuron death but quickly lose their efficacy. Cell therapy for neurodegenerative diseases remains limited because of the difficulty of successfully implanting new tissue into the central nervous system. Development of new drug treatments is similarly stunted because of the imperfection of animal trials and the challenges in growing biomimetic tissue for drug screening. The production of biomimetic neural tissue would allow for large-scale drug discovery and screening. Three-dimensional (3-D) printing offers a streamlined system to engineer cellularly and mechanically accurate neural tissue for drug discovery, or, in the future, for cell therapy. New microfluidic printing platforms such as those designed by Aspect Biosystems offer an increased cellular resolution and printheads which have little impact on cell viability and can print a variety of extrudable polymers such as fibrin, collagen, hyaluronic acid, poly (caprolactone) and poly (ethylene glycol). This work presents the development of an extrudable polymer compatible with Aspect Biosystems 3-D printing technology which supports human-induced pluripotent stem cell differentiation into a neural tissue for use in drug discovery and disease modelling. The polymer bioink is made up of base polymers A and B*, whose concentrations were optimized to increase cell viability. Additives G, P and L were then added to the formulation and their effects on cell differentiation were quantified. These preliminary studies indicate that polymer B may decrease cell proliferation while additive L may increase the number of cells destined for a neuronal fate. Future studies should focus on long-term cell differentiation and replicates.