Bioprinting has evolved into a thriving technology for the fabrication of cell-laden scaffolds. Bioinks are the most critical component for bioprinting. Recently, microgels have been introduced as a very promising bioink enabling cell protection and the control of the cellular microenvironment. However, their microfluidic fabrication inherently seemed to be a limitation.<br/><br/>Here we introduce a direct coupling of microfluidics and 3D-printing for the microfluidic production of cell-laden polymer microgels with direct in-flow bioprinting into stable scaffolds. The methodology enables the continuous on-chip encapsulation of cells into monodisperse microdroplets with subsequent in-flow photocross-linking to produce cell-laden microgels, which after exiting a microtubing are automatically jammed into thin continuous microgel filaments. The integration into a 3D printhead allows direct in-flow printing of the filaments into free-standing three-dimensional scaffolds. The method is demonstrated for physical and photo-chemical cross-linking methods for synthetic polymers and biopolymers. We further show that the printed cell-laden microgel scaffolds have sufficient intrinsic microporosity for continuous permeation of medium, and demonstrate the integration of additional complementary perfusable microchannel systems.

On-chip fabrication and in-flow 3D-printing of cell-laden microgel constructs: From chip to scaffold materials in one integral process

ACS Fall 2021

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