Scientists at Brown University, Rhode Island Hospital, and the Warren Alpert Medical School say they have developed a new instrument that might eventually build replacement human organs the way electronics are assembled today: with precise picking and placing of parts.
In this case, the parts are not resistors and capacitors, but 3-D microtissues containing thousands to millions of living cells that need a constant stream of fluid to bring them nutrients and to remove waste. The researchers have published a paper (“Bio-Pick, Place, and Perfuse: A New Instrument for 3D Tissue Engineering”) in Tissue Engineering Part C, published by Mary Ann Liebert..
“We have developed an innovative instrument, the Bio-Pick, Place, and Perfuse (Bio-P3), which picks up large complex multicellular building parts, transports them to a build area, and precisely places the parts at desired locations while perfusing the parts,” wrote the investigators. These assembled parts subsequently fuse to form a larger contiguous tissue construct.
Because it allows assembly of larger structures from small living microtissue components future versions of BioP3 may finally make possible the manufacture of whole organs such as livers, pancreases, or kidneys, according to Jeffrey Morgan, Ph.D., a Brown University bioengineer and founder of MicroTissues, which sells such culture-making technology.
“For us it's exciting because it's a new approach to building tissues, potentially organs, layer by layer with large, complex living parts,” said Dr. Morgan, who is professor of molecular pharmacology, physiology, and biotechnology. “In contrast to 3-D bioprinting that prints one small drop at a time, our approach is much faster because it uses pre-assembled living building parts with functional shapes and a thousand times more cells per part.”
The BioP3, made mostly from parts available at Home Depot for less than $200, seems at first glance to be a small, clear plastic box with two chambers: one side for storing the living building parts and one side where a larger structure can be built with them. It's what rests just above the box that really matters: a nozzle connected to some tubes and a microscope-like stage that allows an operator using knobs to precisely move it up, down, left, right, out and in.
The plumbing in those tubes allows a peristaltic pump to create fluid suction through the nozzle's finely perforated membrane. That suction allows the nozzle to pick up, carry and release the living microtissues without doing any damage to them, as shown in the paper.
Once a living component has been picked, the operator can then move the head from the picking side to the placing side to deposit it precisely. In the paper, the team shows several different structures made by Andrew Blakely, M.D., a surgery fellow at Rhode Island Hospital, including a stack of 16 donut rings and a stack of four honeycombs. Because these are living components, the stacked microtissues naturally fuse with each other to form a cohesive whole after a short time.
Because each honeycomb slab had about 250,000 cells, the stack of four achieved a proof-of-concept, million-cell structure more than 2 millimeters thick.
That's not nearly enough cells to make an organ such as a liver (an adult's has about 100 billion cells), according to Dr. Morgan, but the stack did have a density of cells consistent with that of human organs. In 2011, Morgan's lab reported that it could make honeycomb slabs 2 centimeters wide, with 6 million cells each. Complex stacks with many more cells are certainly attainable, he said.
In the paper the team made structures with a variety of cell types including H35 liver cells, KGN ovarian cells, and even MCF-7 breast cancer cells (building large tumors could have applications for testing of chemotherapeutic drugs or radiation treatments). Different cell types can also be combined in the microtissue building parts. In 2010, for example, Dr. Morgan collaborated on the creation of an artificial human ovary unifying three cell types into a single tissue.