Selected from stanford.edu
By David Levin
Machine Heart Compilation
Machine Heart Editorial Department
Using advanced 3D printing technology, Stanford researchers converted pastes made from living cells into hearts and other organs.
The heart is the most amazing organ of the human body, its chamber can be pumped evenly for a long time, the material is flexible, and it can be contracted as needed. It's a structural marvel – however, when the heart goes wrong, its inherent complexity makes it a real challenge for repair. As a result, thousands of young people with congenital heart disease must deal with the disease for life.
Mark Skylar-Scott, assistant professor of bioengineering at Stanford University, said, "Pediatric heart disease is one of the most common congenital diseases in the United States. This poses a huge difficulty for the patient's family. Some methods can prolong the lives of children through surgery, but these children will still be limited in their activities and live a life full of uncertainty. Only by replacing damaged or deformed tissue in some way can a truly curative solution be obtained."
Mark Skylar-Scott, assistant professor of bioengineering at Stanford University
That's exactly what Skylar-Scott is studying, who is working on new ways to treat congenital heart disease by building engineered heart tissue in the lab. Skylar-Scott notes that it's not just about growing cells in a Petri dish. Most existing techniques implant heart cells or stem cells into temporary "scaffolds": a porous, spongy substance that fixes cells in three dimensions. Although this method allows researchers to grow tissue in the lab, this method only works on extremely thin cell layers.
"If your scaffold is only a few cells thick, you can put the cells in the right place." But if you're trying to grow something a centimeter thick, it's hard to grow the cells in the right place so that they can grow tissue, and it's hard to keep the cells alive." Skylar-Scott adds that human organs are not a single sphere of cells, each consisting of complex layers of multiple cell types, resulting in 3D structures that are difficult to replicate.
Print organoids
To solve the problem of organ growth, the Skylar-Scott team used advanced 3D printing technology, they made one layer of thick tissue at a time and placed the desired cells in the correct position. Skylar-Scott notes that this construction method is well suited for replicating complex tissues such as the heart, where 3D forms are important.
Despite the promising prospects, cell 3D printing also presents some profound and tricky challenges. Unlike consumer 3D printers, which can heat and squeeze materials of countless shapes, cells are alive and very fragile.
Skylar-Scott said: "If you try to put only one cell at a time, printing a liver or heart can take hundreds or thousands of years. Even if you put 1,000 cells per second, you still need to put billions of cells to get an organ."
Instead, Skylar-Scott's team is speeding up the printing process by placing dense clumps of cells called "organoids." The team created clumps by placing transgenic stem cells into a centrifuge, which produced a paste-like substance. Using this mixture, they were able to print a large number of cells simultaneously into gel-like 3D structures. The large-scale structure of organs is achieved by printing these organoids.
Cell programming
However, putting stem cells in the right place is only the first step. Once they are printed, the researchers must somehow differentiate them into more specific cell types, forming a multi-layered working cluster of cells that resemble healthy organ tissue. To do this, Skylar-Scott soaks stem cells in a chemical mixture.
Each type of stem cell is genetically engineered to respond to a specific drug, and once they feel the drug, the stem cells differentiate into specific cell types. Some cells are programmed to become cardiomyocytes, which form the core functional tissue of the heart. Others are programmed to become stromal cells that bond tissues together.
Skylar-Scott tests printed tissue in a smartphone-sized bioreactor, which helps keep printed cells alive. The team grew an organ-like structure in the bioreactor: a tube about 2 inches long and half a centimeter in diameter that resembles a vein in the human body, a tiny device that pumps, contracts and expands on its own to allow fluid to pass through itself.
extend
Skylar-Scott soon realized that a larger structure, such as a functional chamber that could be transplanted onto an existing heart, should be printed, but there was still a long way to go. This scenario implies a 16-fold increase in size over an experimental venous pump. In order to produce something closer to that size, a completely new organ, the lab needs to dramatically expand cell production.
Skylar-Scott said: "Scaling up the artificial heart only requires building a larger printer, and the key to that is still the cell itself."
"Right now, it takes a month to grow enough cells to print something tiny, but it's also very expensive, costing tens of thousands of dollars per test." We need to find ways to engineer cells to make them stronger and less expensive to grow. Once the tubes for the new cells are in place, I think we're going to start seeing some incredible progress." Skylar-Scott said.