When biologists think about the role of sugar in cellular biology and the respiration of tissues, they’re typically not thinking of the kind you can find in your kitchen cabinet. But for bioengineers at Rice University, that’s a perfect place to start when you want to create blood vessels from scratch.
Using a blend of powdered sugars—and a computer-controlled laser beam capable of fusing the fine grains together—the researchers showed they could build intricate, gossamerlike networks of channels in 3D, capable of serving as blood vessels needed to feed a constructed organ.
"One of the biggest hurdles to engineering clinically relevant tissues is packing a large tissue structure with hundreds of millions of living cells," said Ian Kinstlinger, a bioengineering graduate student in Rice's Brown School of Engineering and lead author of the team’s paper, published in Nature Biomedical Engineering. "Delivering enough oxygen and nutrients to all the cells across that large volume of tissue becomes a monumental challenge.”
The researchers showed their 3D-printed sugar networks could help keep a large amount of densely packed cells alive for two weeks by mimicking human vasculature—a necessary step toward building living tissues capable of addressing disease or injury.
"The 3D-printing process we developed here is like making a very precise creme brûlée," said study co-author Jordan Miller, an assistant professor of bioengineering at Rice.
Using an open-source, modified laser cutter in Miller’s lab, the team was able to build the 3D structure one 2D layer at a time. Known as selective laser sintering, the process is similar to the more commonly used extrusion method of 3D printing, where an object is built with material flowing from an articulated nozzle.
"There are certain architectures—such as overhanging structures, branched networks and multivascular networks—which you really can't do well with extrusion printing," said Miller, who has been working on the laser-sintering approach at Rice since 2013. "Selective laser sintering gives us far more control in all three dimensions, allowing us to easily access complex topologies while still preserving the utility of the sugar material."
Once printed, the sugar network is surrounded by living cells. After the structure begins to solidify, the sugar is dissolved and flushed out of the system with water, leaving open channels behind for the transport of nutrients and oxygen.
The computational algorithm used to generate the treelike vascular architecture was developed in collaboration with Nervous System, a design studio that uses computer simulations to make art, jewelry and housewares.
"We're using algorithms inspired by nature to create functional networks for tissues," said Jessica Rosenkrantz, co-founder and creative director of Nervous System, and a study co-author. "Because our approach is algorithmic, it's possible to create customized networks for different uses."
The team has seeded the linings of the channels with endothelial cells while surrounding them with rodent liver cells.
"We showed that perfusion through 3D vascular networks allows us to sustain these large liverlike tissues,” Miller said. “While there are still long-standing challenges associated with maintaining hepatocyte function, the ability to both generate large volumes of tissue and sustain the cells in those volumes for sufficient time to assess their function is an exciting step forward."