Sacrificial glass lattices made of sugar provide a new way to pattern blood vessels to create large engineered tissues that could be used to construct artificial organs, a team of researchers reports (Nat. Mater., DOI: 10.1038/nmat3357).
Cells in the center of thick lab-grown tissues usually die because they are too far away from a source of nutrients. The lack of methods to incorporate blood vessels remains a major hurdle to growing three-dimensional tissues on the scale needed for artificial organs.
“In our bodies, every cell is probably within a couple hundred micrometers of a capillary blood vessel,” says team leader Christopher S. Chen, a bioengineer at the University of Pennsylvania. Until now, engineered tissues have been limited to 0.5-mm thickness because there haven’t been good ways to vascularize larger tissues.
“The inclusion of vascular structure within 3-D cultures of cells is a crucial step in the realization of the long-term goals of tissue engineering and regenerative medicine,” says Abraham D. Stroock, a bioengineer at Cornell University who is also working to vascularize engineered tissues.
Chen and his coworkers have now come up with a way to make larger tissues than previously had been possible. They use what Chen jokingly calls “dessert technology” to fabricate carbohydrate glass scaffolds that dissolve “just like candy on your tongue” when a gel polymerizes around them. After the solid sugar rods dissolve, they leave behind a network of channels.
The researchers make the glass lattices by extruding a solution of glucose, sucrose, and dextran through the nozzle of a 3-D printer. The dextran gives the lattices the extra stability that structures made of just glucose and sucrose lack. To prevent the lattice from disappearing before the gel can polymerize, the researchers coat the rods with thin polymer layers that dissolve more slowly than the sugar.
The sugar lattice is compatible with a range of polymers that can be used as the gel. That means that the method should work for tissue vascularization no matter what types of matrices or cells are involved. Chen’s group has used the scaffold to make tissues with various cell types, including those from the liver and kidneys.
So far, Chen has made tissues that are bigger than anything previously possible but smaller than he would ultimately like. “We’re pretty comfortable making centimeter-scale tissues,” he says. “To get to heart-sized tissues, you’re going to need larger vessels that branch into smaller ones,” a capability that has not yet been achieved.
“An important open question about their technique is whether it can be used to form smaller vessels that are representative of the microvasculature in human tissues,” Stroock says. “Future efforts that combine microfabrication, printing technologies, and composite materials will allow for the formation of truly physiologically relevant microvasculature and open the door for the growth of appropriate tissues for the clinic.”