3D printing stem cells to create living tissues

UK scientists have developed a method to 3D print stem cells to form complex living 3D structures — a breakthrough that could potentially revolutionise regenerative medicine.

Interest in 3D printing for organ transplantation is increasing as research gains pace. However, printing high-resolution living tissues is challenging — cells often move within printed structures and the soft scaffolds printed to support the cells can collapse on themselves.

Now, researchers led by Professor Hagan Bayley at the University of Oxford have devised a way to produce tissues in self-contained cells that support the structures to keep their shape. Their work has been published in the journal Scientific Reports.

“We were aiming to fabricate three-dimensional living tissues that could display the basic behaviours and physiology found in natural organisms,” said Dr Alexander Graham, a 3D bioprinting scientist at OxSyBio and lead author on the study. “To date, there are limited examples of printed tissues which have the complex cellular architecture of native tissues. Hence, we focused on designing a high-resolution cell printing platform, from relatively inexpensive components, that could be used to reproducibly produce artificial tissues with appropriate complexity from a range of cells, including stem cells.”

The scientists explained how living mammalian cells were contained within protective nanolitre droplets wrapped in a lipid coating that could be assembled, layer by layer, into living structures. Producing printed tissues in this way improves the survival rate of the individual cells and allowed the team to improve on current techniques by building each tissue one drop at a time to a more favourable resolution. Furthermore, the method enables the fabrication of patterned cellular constructs which, once fully grown, mimic or potentially enhance natural tissues — an essential requirement in order for them to be useful.

A confocal micrograph of artificial tissue containing two populations of human embryonic kidney cells (HEK-293T) printed in the form of an arborised structure within a cube. Image credit: Sam Olof.

“The bioprinting approach developed with Oxford University is very exciting, as the cellular constructs can be printed efficiently at extremely high resolution with very little waste,” said Dr Adam Perriman, a co-author on the study from the University of Bristol. “The ability to 3D print with adult stem cells and still have them differentiate was remarkable, and really shows the potential of this new methodology to impact regenerative medicine globally.”

The researchers hope that the materials could have a wide impact on healthcare worldwide, enabling the production of complex tissues and cartilage that would potentially support, repair or augment diseased and damaged areas of the body. Another potential application includes shaping reproducible human tissue models that could take away the need for clinical animal testing. Over the coming months they will work to develop new complementary printing techniques that allow the use of a wider range of living and hybrid materials, to produce tissues at industrial scale.

“There are many potential applications for bioprinting and we believe it will be possible to create personalised treatments by using cells sourced from patients to mimic or enhance natural tissue function,” said Dr Sam Olof, chief technology officer at OxSyBio and a co-author on the study. “In the future, 3D bioprinted tissues maybe also be used for diagnostic applications — for example, for drug or toxin screening.”

Top image caption: The 3D droplet bioprinter producing mm-sized tissues. Image credit: Alexander Graham.