In recent years, 3D printing has evolved dramatically. Once limited to materials like plastic or resin, it now extends to human cells, enabling the creation of living tissues. However, bioprinting remains a slow and limited process—until now. This latest innovation promises to change that.
A team of researchers has introduced a new, cutting-edge bioprinting system that could revolutionize how human tissues are 3D printed. This novel approach uses cell-dense spheroids—tiny aggregates of living cells—as the foundational building blocks for tissue creation. Remarkably, the system prints structures ten times faster than existing techniques while maintaining over 90% cell viability, even enabling direct application onto wounds.
Like building a brick wall — with human cells
Bioprinting is vastly more complex than conventional 3D printing. Instead of inert materials like plastics or metals, it uses living cells that require carefully controlled environments. Traditional bioprinting methods—extrusion-based, inkjet, or laser-assisted—often compromise on critical factors such as speed, precision, or cell viability.
The new system, developed by researchers from Penn State, is called HITS-Bio (High-throughput Integrated Tissue Fabrication System for Bioprinting). It encapsulates living cells in a substrate (like a special type of gel), creating a type of biological ink commonly called “bioink”. After being printed, these cells mature onto the 3D tissue over several weeks. It’s a bit like building a brick wall: the cells are the bricks and the bioink is the mortar, says Ibrahim T. Ozbolat, professor at Penn State and author of the new study.
The problem with this approach is that it’s hard to create structures as dense as those in the human body. Spheroids are promising because they have a cell density similar to human tissue, but you have to place them one by one, which is slow. Furthermore, existing methods often damage the cellular structures during the printing process.
HITS-Bio leverages a digitally controlled nozzle array to simultaneously position multiple spheroids, bypassing the limitations of one-at-a-time approaches used by traditional methods. The DCNA platform allows for the rapid and precise assembly of complex tissue architectures, with bioinks acting as the “cement”.
The researchers organized the nozzles in a 4 by 4 array, essentially printing 16 spheroids simultaneously and placing them on the bioink substrate quickly. The change is simple yet transformative as it enables the creation of multilayered, 3D tissue constructs in a fraction of the time required by conventional methods. It also preserves the cell material without damaging it.
“We can then build scalable structures very fast,” Ozbolat said. “It’s 10 times faster than existing techniques and maintains more than 90% high cell viability.”
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Testing the Technology
The researchers tested out HITS-Bio in two key medical applications: regenerating bone tissue and fabricating cartilage constructs.
The team tested the system on a rat model with critical-sized calvarial defects—serious skull injuries that typically require advanced surgical interventions. Using spheroids derived from human adipose stem cells, which were preprogrammed to promote bone growth, HITS-Bio achieved nearly complete defect closure in just six weeks. High-density arrangements of spheroids led to impressive bone coverage rates of up to 96%, with histological studies confirming strong mineralization and integration of new bone tissue.
In another experiment, researchers used HITS-Bio to fabricate a 1 cm³ cartilage construct from 576 spheroids. The entire process took under 40 minutes, which is remarkably fast. These cartilage constructs exhibited high cell viability, robust extracellular matrix deposition, and the expression of key cartilage markers, making them a potential solution for repairing volumetric cartilage defects.
“Since we delivered the cells in high dosages with this technique, it actually sped up the bone repair,” Ozbolat said.
Big implications
The implications of HITS-Bio are immense. This system could bioprint tissue patches directly onto injuries, such as bone fractures or cartilage damage, potentially transforming surgical interventions. Beyond that, it could fabricate customized tissue constructs for transplantation or small-scale functional tissues for specific medical needs.
However, challenges remain. While successful in animal models, the technique requires extensive trials to ensure its safety and effectiveness in humans. Scaling the process for larger human tissues without losing precision is another hurdle.
Despite these obstacles, HITS-Bio represents a major step forward in bioprinting technology, opening doors to faster, more reliable, and scalable production of living tissues. Researchers are now working on techniques that can incorporate blood vessels into the fabricated tissue, a necessary step for producing more types of tissues.
The study was published in Nature Communications.
