In situ bioink mixing during 3D bioprinting is now a possibility

Researchers at the Massachusetts Institute of Technology (MIT) have developed a magnetically actuated mixing platform called MagMix that integrates directly into standard extrusion 3D bioprinters. The solution addresses a long-standing challenge around gravity-driven cell sedimentation during long-duration print jobs. 

The study demonstrated that the compact, modular system maintained uniform cell distribution across 12 consecutively printed tissue constructs over 45-minute print sessions, without altering bioink formulation or requiring permanent hardware modifications to existing equipment.

Extrusion-based 3D bioprinting is a widely used technique in tissue engineering that deposits cell-laden hydrogel bioinks layer by layer through a nozzle. The tendency of cells to settle under gravity inside the extrusion syringe has been an issue that has previously caused multiple issues: the separation degrades cell distribution uniformity, increases the risk of nozzle clogging, and introduces batch-to-batch variability in the resulting tissue constructs. This limits reproducibility for clinical and translational applications.

MagMix used an internal propeller, housed inside the extrusion syringe, that was driven by an external magnet attached to a servo motor controlled via an Arduino Nano microcontroller. The setup applied vertical reciprocating motion to maintain continuous bioink agitation during printing.

The MIT team iterated through three propeller geometries, using computational fluid dynamics simulations in COMSOL Multiphysics to model particle distribution before fabricating and validating the designs experimentally. The third propeller design, which included a screw-like extension to reach the conical tip of the syringe, produced the most homogeneous particle distribution across the syringe cross-section.

Constructs printed with MagMix actively maintained consistent cell viability and density across all 12 sequential prints, while unmixed controls showed progressive cell loss and repeated nozzle-clogging events requiring manual intervention.

The team also evaluated the effect of mixing speed on cell health across three settings. Cell viability measured 90.1 percent at low speed, 82.1 percent at medium speed, and 65.5 percent at high speed, leading the researchers to select the lower two speeds for subsequent experiments. 

The MagMix platform was fabricated using low-cost 3D-printed components, with the bioink-contacting propeller printed in biocompatible Vero ContactClear resin. The system was designed to be compatible with a range of syringe sizes and commercial or custom extrusion bioprinters.