So, here's something you can do with that cotton-candy machine that has been gathering dust in the back of your kitchen cabinet: Instead of sugar, throw in a polymer and, presto, spin out some artificial capillary systems, a necessary step to the ultimate creation of artificial organs. The process is a bit more complicated than that but, in essence, that's what Leon Bellan, Assistant Professor of mechanical engineering at Vanderbilt University, has achieved. In an article published online by Advanced Healthcare Materials on Feb. 4, Bellan and his team of researchers reported that they were successful at producing a three-dimensional artificial capillary system that can keep living cells viable and functional for more than a week. And it all started with a $40 cotton-candy machine Bellan bought at Target.
While attending a lecture on tissue engineering that discussed the need to create an artificial vascular system to support cells in thick engineered tissue, it occurred to Bellan, then a graduate student, that electrospinning can produce networks resembling capillaries on a very small scale.
"The analogies everyone uses to describe electrospun fibers are that they look like silly string, or Cheez Whiz, or cotton candy," Bellan told David Salisbury, who reported on the project for Research News @ Vanderbilt. "So I decided to give the cotton candy machine a try. I went to Target and bought [one] for about $40. It turned out that it formed threads that were about one-tenth the diameter of a human hair—roughly the same size as capillaries—so they could be used to make channel structures in other materials." Getting from there to the point of publishing a paper on the succesful application of that technology required considerable tinkering, of course, as well as finding a suitable material.
Because their properties can be tuned to mimic the biological material that surrounds cells in the body, hydrogels are typically used to build scaffolds that support cells within artificial organs. But, notes Salisbury, if you create a network of fibers using sugar, when you pour a hydrogel—which is mostly water—on it, the sugar dissolves. To create a viable artificial sacrificial structure, "the material has to be insoluble in water when you make the mold, so it doesn't dissolve when you pour the gel," explains Bellan. "Then it must dissolve in water to create the micro channels, because cells will only grow in aqueous environments." The solution proved to be a polymer—PNIPAM, Poly (N-isopropylacrylamide)—which is insoluble at temperatures above 32° C and soluble below that temperature.
Here is how it works, as described in Research News @ Vanderbilt:
The researchers first spin out a network of PNIPAM threads using a machine closely resembling a cotton-candy machine. Then they mix up a solution of gelatin in water (a liquid at 37°) and add human cells, like adding grapes to jello. Adding an enzyme commonly used in the food industry (transglutaminase, nicknamed "meat glue") causes the gelatin to irreversibly gel. This warm mixture is poured over the PNIPAM structure and allowed to gel in an incubator at 37°. Finally, the gel containing cells and fibers is removed from the incubator and allowed to cool to room temperature, at which point the embedded fibers dissolve, leaving behind an intricate network of microscale channels. The researchers then attach pumps to the network and begin perfusing them with cell culture media containing necessary chemicals and oxygen.
Bellan's cotton-candy spinning technique can produce channels ranging from 3 to 55 microns, with a mean diameter of 35 microns. Other methods have been unable to create networks with micro channels smaller than 100 microns, about 10 times the size of capillaries, notes Bellan.
"Our experiments show that, after seven days, 90% of the cells in a scaffold with perfused micro channels remained alive and functional compared to only 60 to 70% in scaffolds that were not perfused or did not have micro channels," Bellan reported.
To learn more, watch the video embedded below. But first grab a snack or two; you might get a craving for some sweets.