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Cotton candy machines can hold key to making artificial organs

Cotton candy machines can hold key to making artificial organs

Cotton candy machines may hold the key for making life-sized artificial livers, kidneys, bones and other essential organs.

For several years, Leon Bellan, assistant professor of mechanical engineering at Vanderbilt University, has been tinkering with cotton candy machines, getting them to spin out networks of tiny threads comparable in size, density and complexity to the patterns formed by capillaries - the tiny, thin-walled vessels that deliver oxygen and nutrients to cells and carry away waste. His goal has been to make fiber networks that can be used as templates to produce the capillary systems required to create full-scale artificial organs.

In an article published online by the Advanced Healthcare Materials journal, Bellan, and colleagues report that they have succeeded in using this unorthodox technique to produce a three-dimensional artificial capillary system that can keep living cells viable and functional for more than a week, which is a dramatic improvement over current methods.

Some people in the field think this approach is a little crazy, said Bellan, But now we've shown we can use this simple technique to make microfluidic networks that mimic the three-dimensional capillary system in the human body in a cell-friendly fashion. Generally, it's not that difficult to make two-dimensional networks, but adding the third dimension is much harder; with this approach, we can make our system as three-dimensional as we like.

Many tissue engineering researchers, including Bellan, are currently focusing their efforts on a class of materials similar to hair gel - water-based gels, called hydrogels - and using these materials as scaffolds to support cells within three-dimensional artificial organs.

Hydrogels are attractive because their properties can be tuned to closely mimic those of the natural extracellular matrix that surrounds cells in the body. Unlike solid polymer scaffolds, hydrogels support diffusion of necessary soluble compounds; however, oxygen, nutrients and wastes can only diffuse a limited distance through the gel.

So, to engineer tissues that have the thickness of real organs and keep cells alive throughout the entire scaffold, the researchers must build in a network of channels that allow fluids to flow through the system, mimicking the natural capillary system.

There are two basic methods that researchers use to create artificial capillary systems: bottom-up and top-down.

In the bottom-up process, scientists culture cells in a thin slab of gel, and after some time they spontaneously begin creating capillaries. Although this approach has the advantage of simplicity, it has one fundamental problem.

As a result, Bellan is using a top-down approach. He reports that his cotton-candy spinning method can produce channels ranging from three to 55 microns, with a mean diameter of 35 microns. So far the other top-down approaches have only managed to create networks with microchannels larger than 100 microns, about ten times the size of capillaries, he said. In addition, many of these other techniques are not able to form networks as complex as the cotton candy approach.

The researchers experimented with a number of different materials before they discovered one that worked. The key material is PNIPAM, Poly (N-isopropylacrylamide), a polymer with the unusual property of being insoluble at temperatures above 32 degrees Celsius and soluble below that temperature. In addition, the material has been used in other medical applications and has proven to be rather cell-friendly.

Our experiments show that, after seven days, 90 percent of the cells in a scaffold with perfused microchannels remained alive and functional compared to only 60 to 70 percent in scaffolds that were not perfused or did not have microchannels, Bellan reported.

Now that Bellan and his team have shown that this technique works, they will be fine-tuning it to match the characteristics of the small vessel networks in different types of tissues, and exploring a variety of cell types.

Cotton candy machines can hold key to making artificial organs