A new approach to 3D printing human organs
Adding blood vessels overcomes important limitations. Paul Biegler reports.
Scientists have taken cues from the “lost wax” technique for making renaissance bronzes to 3D print human mini-organs with their very own blood vessels.
It’s an advance that moves the field closer to creating life-saving organ transplants for the more than 100,000 people on US waiting lists alone, 20 of whom die each day.Mini versions of the brain, kidney and heart – so-called “organoids” – have been grown in labs for the last decade to study diseases including dementia, cancer and heart attacks.
But those models have stayed tiny, up to the size of a lentil, because of a critical ceiling. They lack tubes that mimic blood vessels and so researchers have struggled to get oxygen and nutrients into their core.
That crucial limitation has, thus far, put the kibosh on organoids fulfilling their grail-like destiny – to become full size transplant organs right there in the lab, tailor-made from patients’ own cells and not subject to rejection.
Now researchers, led by Jennifer Lewis at the Wyss Institute for Biologically Inspired Engineering at Harvard University in the US, have come up with an ingenious way of sculpting channels that meander like real blood vessels through mini-organs.
It even comes with its own, rather gothic moniker – Sacrificial Writing into Functional Tissue, or SWIFT.
They start by making “organ building blocks” from human stem cells, which they chemically cajole into becoming mini hearts and brains.
Hundreds of thousands of those organ breeze blocks are mixed into a slurry and compacted, at low temperature, to form a matrix of cells with roughly the density of human tissue.
Then they make the magic happen.
Using a 3D printer, a nozzle containing an ink made of red dye and gelatin descends into the mixture, depositing its contents through the cell matrix according to a pre-ordained branch pattern.
Once the network is printed, they heat the mix to 37 degrees Celsuis. The ink melts, leaving channels which the researchers line with the endothelial cells found in human vessels.
Donatello would surely approve – it’s a step not unlike the melting of wax to make bronze castings in quattrocento Florence.
All that is left is to perfuse the mini-organs with a liquid rich in oxygen and nutrients. When the team did this, they kept a 1.5-centimetre mini-heart beating on its own for more than a week.
"Forming a dense matrix from these organ building blocks kills two birds with one stone: not only does it achieve a high cellular density akin to that of human organs, but the matrix's viscosity also enables printing of a pervasive network of perfusable channels within it to mimic the blood vessels that support human organs," says co- author Sébastien Uzel from the Wyss Institute.
The researchers couldn’t, however, resist adding a couple of cadenzas to their feat.
They injected a drug through those vessels that increases heart rate in people. It promptly doubled the pace of the mini-heartbeat. They also made a wedge of heart tissue and 3D-printed a replica of the main coronary artery and one of its branches onto it – which could be very handy for any future heart transplant.
"The ability to support living human tissues with vascular channels is a huge step toward the goal of creating functional human organs outside of the body," says Wyss Institute Founding Director Donald Ingber.
You may, or may not, wish to call them cell sculptors of the bio-renaissance.
The study appears in the journal Science Advances.