3D bioprinting using hollow multifunctional fiber impedimetric sensors

Abstract

3D bioprinting is an emerging biofabrication process for the production of adherent cell-based products, including engineered tissues and foods. While process innovations are rapidly occurring in the area of process monitoring, which can improve fundamental understanding of process-structure-property relations as well as product quality by closed-loop control techniques, in-line sensing of the bioink composition remains a challenge. Here, we report that hollow multifunctional fibers enable in-line impedimetric sensing of bioink composition and exhibit selectivity for real-time classification of cell type, viability, and state of differentiation during bioprinting. Continuous monitoring of the fiber impedance magnitude and phase angle response from 10(2)to 10(6)Hz during microextrusion 3D bioprinting enabled compositional and quality analysis of alginate bioinks that contained fibroblasts, neurons, or mouse embryonic stem cells (mESCs). Fiber impedimetric responses associated with the bioinks that contained differentiated mESCs were consistent with differentiation marker expression characterized by immunocytochemistry. 3D bioprinting through hollow multifunctional fiber impedimetric sensors enabled classification of stem cells as stable or randomly differentiated populations. This work reports an advance in monitoring 3D bioprinting processes in terms of in-line sensor-based bioink compositional analysis using fiber technology and provides a non-invasive sensing platform for achieving future quality-controlled bioprinted tissues and injectable stem-cell therapies.