Published on 20 Mar 2026

Solving Bioprinting’s Temperature Problem

Bioprinting seeks to produce lab-grown human tissue on demand, but keeping living cells healthy while printing complex shapes has long held the field back. Researchers at NTU have now found a way to print bioink at body temperature without losing structural control, bringing engineered organs closer to reality.

The demand for functional human tissue used in regenerative medicine and drug development is growing as people live longer and treatments become more ambitious. Yet donor material is scarce and hard to manage.

This issue makes the prospect of simply 3D printing new tissue irresistibly pragmatic.

Prof Bartolo and his team (Left to right) Prof Paulo Bartolo, Researcher Boyang Huang and Researcher Cian Vyas
with the BIO X6 extrusion-based 3D bioprinter

While it might sound like science fiction, bioengineered tissue is used every day in research labs around the world, thanks to the work of engineers like Executive Director of the Singapore Centre for 3D Printing (SC3DP) and Professor of NTU Engineering’s School of Mechanical and Aerospace Engineering (MAE), Paulo Bartolo.

And after spending their careers developing suitable materials to make it possible, Bartolo and colleagues have now broken through a long-held problem in the field. They’ve devised a way to keep the printing bioink at a temperature that maintains cell and tissue health without sacrificing its ability to hold shape.

Temperature vs viscosity

At its core, bioprinting works much like ordinary 3D printing. A computer guides a nozzle to deposit material layer by layer, gradually building a three-dimensional shape in a process known as direct printing.

But unlike ordinary 3D printing that uses materials like plastic, the printer uses a special gel of living cells called bioink. Those cells are first grown in the lab, then collected and blended into the gel to create a printable, living mixture.

3D printed cornea, courtesy of the SC3DP

The cells remain delicate, staying healthiest when handled gently and kept close to a physiological body temperature of around 37ºC.

Unfortunately, this isn’t the optimal temperature for producing material that is both printable and will maintain the complex shapes necessary to produce a tissue or organ.

“At body temperature, conventional hydrogels lose viscosity, making it hard to produce well-defined, stable structures,” explained researcher Boyang Huang. “You can increase viscosity to improve printability, but it risks exposing the cells to damaging stresses during extrusion.”

Another method of printing, known as embedded printing, has the bioink printed inside a supportive gel or bath, which acts like a temporary scaffold for shaping more delicate structures. It can tolerate a wider range of temperatures, but not for the multiple hours it takes to print more complex tissues.

Extended fabrication time becomes especially problematic for larger constructs, where cells may be kept outside physiological conditions long enough to trigger stress or cell death. It is one of the reasons engineering of entire organs has remained elusive.

“In 2005, I attended a meeting at the National Science Foundation in the United States. It was the early days of tissue engineering, and everyone wanted a clear target, so we agreed we should be able to print a kidney by 2020,” stated the professor. “It’s now 2025, and we still don’t have that capability.”

“We’re getting closer to organ printing now that we’ve shown we can successfully expand bioprinting capability at body temperature for both direct and embedded bioprinting,” he added.

Devising a balancing act

By blending gelatin methacryloyl (GelMA) with methylcellulose (MC/MCMA), the team paired two polymers that react differently to heat, one stiffening as it cools, the other as it warms. Together, the polymers create a material with a stable, predictable viscosity across a broader temperature range, including the 37ºC needed to keep cells healthy.

To lock the printed structure into place, the researchers added a light-activated setting step that triggers the polymers to form a stable network.

This combination of thermal responsiveness and photochemical stability makes the material unusually adaptable. It can be extruded directly onto a surface in neat, self-supporting lines or be used as a support bath to allow complex printing such as blood vessel networks.

The result was a single bioink that works well in both direct and embedded printing, flows smoothly during extrusion, is considered self-healing as it quickly rebuilds its structure afterward, and keeps the cells inside it safe and healthy.

The team didn’t stop at proving the material could be printed; they needed to show that living cells could actually thrive inside it. In a series of live-cell tests using human adipose-derived stem cells, printed structures at body temperature showed more than 90 per cent viability, indicating the bioink shields cells from mechanical stress.

Furthermore, once embedded in the printed structures, the cells began to spread and proliferate, their behaviour shifting depending on the polymer concentration and cell density. That response suggests the material isn’t just a temporary carrier but a supportive environment capable of nurturing early tissue development and hints at longer-term regenerative potential.

“What we demonstrate in this paper is that we are able to tune these materials for different types of tissue and printing applications,” detailed study co-author Cian Vyas.

Researcher Boyang Huang loads the BIO X6 extrusion-based 3D bioprinting device

Are organs on the horizon?

According to Bartolo, the first major hurdle in bioprinting was developing materials that could support living cells. With those materials now in place, he points to two more challenges: biomaterials that guide cells to form bone, skin or other tissues, and hardware capable of printing complex tissues.

Tissues range in complexity, with different regions having their own demands, even within the same construct. Cartilage, pancreas, and vascular channels each require their own mechanical cues and resolutions, and no single machine can yet shift effortlessly between them.

“There is still no commercial system capable of seamlessly integrating multiple 3D printing technologies and operating across the diverse scales required for functional organs,” he explained.

He added that his teams are currently trying to combine different technologies to address multi-material, hierarchical, complex tissues. “The field is progressing very fast,” the professor conceded.

A printed kidney may still not be on the horizon for the industry five years past the deadline, but the science is undeniably closing the distance. If the materials are now ready, the machines may soon follow.

Rethinking how things are made

When Bartolo relocated from the UK to Singapore in 2021 to become Executive Director of the SC3DP, the centre was already well established. At the time, its strengths lay in aerospace, construction, and marine engineering. Bioprinting existed, but without a clear centre of gravity.

Bartolo holds a printed aircraft nozzle in front of the centre’s LaserTec 65 3D printing machine

Bartolo’s arrival brought an opportunity to turn healthcare into a core research pillar and build a coherent programme around biomedical application. Today, SC3DP is one of only a handful of research centres worldwide combining multi-sector 3D printing expertise with scalable facilities and deep industry collaboration. That reach has enabled partnerships with global players such as Boeing, Aramco and Panasonic, alongside advanced manufacturing leaders including Makino, Evonik and Arkema.

For Bartolo, the technology is about more than machines. “3D printing allows us a chance to rethink how things are made,” he said. Traditional manufacturing cuts from solid blocks and discards the rest; additive manufacturing builds only what is needed.

That philosophy stands on display in an unlikely showpiece on the centre floor: a prefabricated bathroom unit printed with a lattice structure that reduced material use, cutting costs by 34 per cent and CO₂ emissions by 86 per cent. The amusing part, noted Bartolo, is that despite prominent warning signs that it is only a display, centre visitors still try to use it. “People think it works all the time,” Bartolo laughed. “We have to stop them.”

Story by Laura Dobberstein, NTU College of Engineering

This story also appeared in the 2026 NTU Engineering Annual Magazine.