3D bioprinting, in which living tissues are printed using cells mixed into tender hydrogels, or “bio-inks”, is widely used in the field of bioengineering to model or replace tissues in our bodies. However, print quality and tissue repeatability can pose challenges. One of the most significant challenges is simply gravity – cells naturally sink to the bottom of the bioink extrusion printer syringe because they are heavier than the surrounding hydrogel.
“Cell settling, which is exacerbated by the long printing sessions required to print large tissues, leads to clogged nozzles, uneven cell placement, and inconsistencies between printed papers,” explains Ritu Raman, Eugene Bell Career Development Professor of Tissue Engineering and assistant professor of mechanical engineering at MIT. “Existing solutions, such as manually mixing bioinks before loading them into the printer or using passive mixers, are unable to maintain uniformity once printing begins.”
In study published Feb. 2 in the journal Raman’s team introduces a fresh approach that aims to address this fundamental limitation by actively preventing cell sedimentation in bioinks during printing, enabling 3D printing of more reliable and biologically coherent tissues.
“Precise control over the physical and biological properties of the bioink is essential to reproduce the structure and function of native tissues,” says Ferdows Afghah, a doctoral candidate in mechanical engineering at MIT and lead author of the study.
“If we can print tissues that better mimic those found in our bodies, we can use them as models to better understand human diseases or test the safety and effectiveness of new therapeutic drugs,” adds Raman. Such models could lend a hand scientists move away from techniques such as animal testing, which are becoming increasingly popular interest from the U.S. Food and Drug Administration to develop faster, cheaper and more informative fresh approaches to establish the safety and effectiveness of fresh treatment pathways.
“Ultimately, we are working on applications of regenerative medicine, such as replacing diseased or damaged tissues in our bodies with 3D printed tissues that can help restore healthy function,” Raman says.
MagMix, a magnetically actuated mixer, consists of two parts: a diminutive magnetic propeller that fits into syringes used by bioprinters to deposit bioink layer by layer into 3D tissues, and a constant magnet attached to a motor that moves up and down near the syringe, controlling the movement of the propeller inside. Collectively, this compact system can be mounted on any standard 3D bioprinter, maintaining even bioink mixing during printing without changing the bioink composition or disrupting normal printer operation. To test this approach, the team used computer simulations to design the optimal geometry and speed of the mixing propeller and then verified its performance experimentally.
“For multiple types of bioinks, MagMix prevented cell settling for over 45 minutes of continuous printing, reducing clogging and maintaining high cell viability,” says Raman. “Importantly, we have shown that mixing speeds can be adjusted to balance effective homogenization of different bioinks while inducing minimal cell stress. As a proof of concept, we have demonstrated that MagMix can be used to 3D print cells that can mature into muscle tissue within days.”
By maintaining an even cell distribution during long and complicated printing jobs, MagMix enables the production of high-quality tissues with more consistent biological functions. Because the device is compact, affordable, configurable, and simple to integrate with existing 3D printers, it provides a widely available solution for laboratories and industries working on reproducible artificial tissues for human health applications, including disease modeling, drug screening, and regenerative medicine.
This work was partially supported by, among others, Safety, Health and Environment Research Laboratory (SHED) at MIT, which provides the infrastructure and interdisciplinary expertise to lend a hand translate biofabrication innovations from laboratory-scale demonstrations to scalable, reproducible applications.
“At SHED, we are focused on accelerating the translation of innovative methods into practical tools that researchers can reliably deploy,” says Tolga Durak, founder of SHED. “MagMix is a strong example of how the right combination of technical infrastructure and interdisciplinary support can move biofabrication technologies toward scalable real-world impact.”
SHED’s commitment reflects a broader vision of strengthening technology pathways that augment reproducibility and accessibility in engineering and life sciences by ensuring equitable access to advanced equipment and supporting interdisciplinary collaboration.
“As we move toward larger-scale and more standardized systems, integrated laboratories like SHED are essential to building sustainable performance,” adds Durak. “Our goal is not only to enable discovery, but also to ensure that new technologies can be reliably implemented and maintained over time.”
The team is also interested in non-medical applications of modified tissues, such as using printed muscles to power safer and more productive “biohybrid” robots.
Scientists believe this work can improve the reliability and scalability of 3D bioprinting, making the potential impact on the field of 3D bioprinting and human health significant. Their article “Increasing bioink uniformity in 3D bioprinting by extrusion with in situ active magnetic mixing”, is now available in the magazine.