Using Cotton Candy Machines to Create Synthetic Blood Vessels

The topic of tissue engineering comes up from time to time here, and I ran across a story in Design News that I thought was really cool.  Dr. Leon Ballan of Vanderbilt University has developed a way to use a cotton candy machine to create networks of tiny blood vessels - capillaries - that are essential to grow other tissues on.

Leon Bellan, assistant professor of mechanical engineering at Vanderbilt University, said he began working with a cotton-candy machine several years ago as a graduate student. He used a process called electrospinning to make nanofibers to form nanochannels, which led him to the idea that it could be used to form artificial capillary system, he told Design News.

During his research Bellan said that by chance he spoke with a reconstructive surgeon, who mentioned that a major hurdle in the field of tissue engineering was the difficulty of building a vascular network.  

“I figured that my nanofibers and nanochannels looked like capillaries, but were too small, so I had the idea to try cotton candy instead,” he said in an interview. Bellan paid about $40 for his first machine at a local Target store.  

His team eventually built a custom fiber-spinning device to makes fibers from solution for their latest research -- a paper about which has been published in Advanced Healthcare Materials -- but it is still “effectively a cotton candy machine,” Bellan added.

Of course it's not just as simple as buying a cotton candy machine and dumping some sugar in it; and it's a modified cotton candy machine, no longer the $40 machine from Target.  If an experimenter creates a network of fibers using sugar, when they pour a hydrogel on it, the sugar dissolves away because the hydrogel is mostly water.  The key was to have a chemical with the right physical characteristics.  

“First, the material has to be insoluble in water when you make the mold so it doesn’t dissolve when you pour the gel. Then it must dissolve in water to create the microchannels because cells will only grow in aqueous environments,” Bellan said. 

After experimenting with many different materials, Bellan's group discovered that 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 cell-friendly.  

A three-dimensional slab of gelatin that contains a microvascular network. (Bellan Lab / 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 degrees) 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 degrees. 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.

Experimentally, they've shown that in their perfused microchannels, 90 percent of the cells in a scaffold remained alive and functional after seven days, compared to only 60 to 70 percent in scaffolds that were not perfused or did not have microchannels.  Their task now is to develop methods that will allow other researchers to create the artificial vasculature needed to sustain artificial livers, kidneys, bone and other organs 

Tissue engineering at the level of growing replacement parts for those damaged by injury or disease has remained elusive.  As with this example, it appears that the key is to develop the right substrates so that the required 3D structures can organically form.  As an engineer, it has always seemed to be to be the real answer to a lot of problems.  

15 years ago a technician I was working with asked me if I'd like to live forever.  I surprised him by saying no.  Tissue engineering might provide an exception.  I think his idea came from someone (Ray Kurzweil?), who said if we can survive until the year 2030, we will have the option of immortality.  I think that's wildly optimistic.  Before that would be reasonable, every disease would have to be cured, and it would have to be possible to surgically fix or grow a replacement for every part of the body.  Spinal cord repair would have to be as reliable as changing a fuse in a car.  All those annoying things that happen as you age would have to be eradicated; things like old injuries turning arthritic, deteriorating hearing, metabolic problems, all the rest.  Not to mention replacing all the scars from every little cut and injury, lest we turn into one continuous mass of scar tissue.  Forever is a long time, and I don't think the futurists have really thought it through.