In recent years, 3D printing has evolved dramatically. Once limited to materials such as plastic or resin, it now extends to human cells and enables the formation of living tissue. However, bioprinting remains – for now – a slow and limited process. This latest innovation promises to change that.
A team of researchers has introduced a new, cutting-edge bioprinting system that could revolutionize the way human tissue is 3D printed. This novel approach uses cell-dense spheroids – tiny aggregates of living cells – as the basic building blocks for tissue formation. Remarkably, the system prints structures ten times faster than existing techniques while maintaining cell viability of over 90% and even allows for direct application to wounds.
Like building a wall – with human cells
Bioprinting is much more complex than traditional 3D printing. Instead of inert materials such as plastics or metals, living cells are used, which 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 Penn State researchers, 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 referred to as “bioink.” After printing, these cells mature into 3D tissue over several weeks. It's a bit like building a wall: The cells are the bricks and the bioink is the mortar, says Ibrahim T. Ozbolat, a professor at Penn State and an author of the new study.
The problem with this approach is that it is difficult 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 individually, which is slow. In addition, existing methods often damage the cellular structures during the printing process.
HITS-Bio uses a digitally controlled nozzle array to position multiple spheroids simultaneously, circumventing the limitations of standalone approaches of traditional methods. The DCNA platform enables the rapid and precise construction of complex tissue architectures, with bioinks acting as “cement”.
The researchers organized the nozzles in a 4×4 arrangement, essentially printing 16 spheroids at once and quickly placing them on the bioink substrate. The change is simple yet transformative, allowing the creation of multi-layered 3D tissue constructs in a fraction of the time required by traditional methods. In addition, the cell material is protected without damaging it.
“We can then build scalable structures very quickly,” said Ozbolat. “It is ten times faster than existing techniques and ensures over 90% high cell viability.”
Testing the technology
The researchers tested HITS-Bio in two important medical applications: the regeneration of bone tissue and the production of cartilage constructs.
The team tested the system on a rat model with critical-sized skull defects – severe skull injuries that typically require advanced surgical procedures. Using spheroids made from human fat stem cells that were pre-programmed to promote bone growth, HITS-Bio achieved almost complete closure of the defect in just six weeks. High-density arrays of spheroids resulted in 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 create a 1 cc cartilage construct from 576 spheroids. The entire process took less than 40 minutes, which is remarkably quick. These cartilage constructs demonstrated high cell viability, robust extracellular matrix deposition, and expression of key cartilage markers, making them a potential solution for the repair of volumetric cartilage defects.
“Because we administered the cells at high doses with this technique, bone repair actually accelerated,” Ozbolat said.
Big implications
The impact of HITS-Bio is immense. This system could bioprint patches of tissue directly onto injuries such as bone fractures or cartilage damage, potentially transforming surgical procedures. In addition, tailored tissue constructs for transplantation or small-scale functional tissues could be produced for specific medical needs.
However, challenges remain. Although the technique is successful in animal models, extensive testing is required to ensure its safety and effectiveness in humans. Another hurdle is scaling the process to larger human tissues without losing precision.
Despite these obstacles, HITS-Bio represents a major advance in bioprinting technology and opens doors for faster, more reliable and scalable production of living tissues. Researchers are currently working on techniques that allow blood vessels to be integrated into the manufactured tissue – a necessary step for the production of other types of tissue.
The study was published in Nature Communications.