Bioengineering researchers around the world are making important strides in the field of bioprinting, moving forward towards the day when we’ll be able to 3D print and transplant complete organs such as livers. We’ve already seen Surgeon Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, 3D print bladders with much success. They and others like a team at the University of Pennsylvania we’ll look at in this article are leading the way towards a future where we will no longer rely on organ donors. In twenty years, the whole concept of donating organs will seem absolutely archaic.
One of the issues holding back researchers from printing large three dimensional organs is something called perfusion: being able to pump blood through tissue so the cells don’t suffocate. The organs require blood vessels in the tissue to deliver nutrients and remove waste products, and creating these vessels has bees problematic.
Thin layers of human tissue are not a problem. But when bioengineers use a 3D printer to create thick tissue or an entire organ, they need to find a way to produce the blood vessels as well. Creating this vasculature structure with a 3D printer has been a big challenge, since attempts at creating hollow channels to mimic blood vessels resulted in structural seams that can push apart from the blood pressure.
But now researchers at the University of Pennsylvania have come up with a novel approach. The team is led by postdoctoral fellow Jordan S. Miller and Christopher S. Chen, the Skirkanich Professor of Innovation in the Department of Bioengineering at Penn, along with Sangeeta N. Bhatia, Wilson Professor at the Massachusetts Institute of Technology, and postdoctoral fellow Kelly R. Stevens in Bhatia’s laboratory.
The new approach is to focus on the vasculature first. What they did is design “free-standing 3D filament networks in the shape of a vascular system that sat inside a mold. As in lost-wax casting, a technique that has been used to make sculptures for thousands of years, the team’s approach allowed for the mold and vascular template to be removed once the cells were added and formed a solid tissue enveloping the filaments.”
But in order for this to work, they needed the right material with which to build the vascular system. It had to be rigid enough keep its three dimensional form, needed to be compatible with a 3D printer, and it also had to be able to dissolve in water without introducing toxicity in the cells.
They came up with something. Here’s how Penn’s site describes the formula:
The formula they settled on — a combination of sucrose and glucose along with dextran for structural reinforcement — is printed with a RepRap, an open-source 3D printer with a custom-designed extruder and controlling software. An important step in stabilizing the sugar after printing, templates are coated in a thin layer of a degradable polymer derived from corn. This coating allows the sugar template to be dissolved and to flow out of the gel through the channels they create without inhibiting the solidification of the gel or damaging the growing cells nearby. Once the sugar is removed, the researchers start flowing fluid through the vascular architecture and cells begin to receive nutrients and oxygen similar to the exchange that naturally happens in the body.
Their experiments in the labs have shown promising results. I won’t try to explain the medical science to you, as I’m just interested here in the 3D printing aspect. If you read the original article you’ll understand it better than I could ever try to explain it to you.
Apologies to Penn for quoting so much of their article below, but I want to point out what they said about using a 3D printer for this process:
With promising indications that their vascular networks will be compatible with all types of cells and gels, the team believes their 3D printing method will be a scalable solution for a wide variety of cell- and tissue-based applications because all organ vasculature follows similar architectural patterns.
“Cell biologists like the idea of 3D printing to make vascularized tissues in principle, but they would need to have an expert in house and highly specialized equipment to even attempt it,” Miller said. “That’s no longer the case; we’ve made these sugar-based vascular templates stable enough to ship to labs around the world.”
Beyond integrating well with the world of tissue engineering, the researchers’ work epitomizes the philosophy that drives much of the open source 3D printing community.
“We launched this project from innovations rooted in RepRap and MakerBot technology and their supporting worldwide communities,” Miller said. “A RepRap 3D printer is a tiny fraction of the cost of commercial 3D printers, and, more important, its open-source nature means you can freely modify it. Many of our additions to the project are already in the wild.”
Several of the custom parts of the RepRap printer the researchers used to make the vascular templates were printed in plastic on another RepRap. Miller will teach a class on building and using these types of printers at a workshop this summer and will continue tinkering with his own designs.
“We want to redesign the printer from scratch and focus it entirely on cell biology, tissue engineering and regenerative medicine applications,” Miller said.
Their work was published in the journal Nature Materials.
Source: University of Pennsylvania