To mimic this architectural complexity in their engineered tissues, the researchers embedded a mixture of brain cells taken from the primary cortex of rats into sheets of hydrogel. They included components of the extracellular matrix, which provides structural support and helps regulate cell behavior.
Those sheets were then stacked in layers, which can be sealed together using light to crosslink hydrogels. By covering layers of gels with plastic photomasks of varying shapes, the researchers could control how much of the gel was exposed to light, thus controlling the 3-D shape of the multilayer tissue construct.
The process used is similar to the photolithography process used in semiconductor manufacturing. But unlike semiconductor photomasks—which can cost hundreds of thousands of dollars—the research team developed a much less expensive way to assemble tissues using masks made from sheets of plastic, similar to overhead transparencies, held in place with alignment pins, they said.
The tissue cubes can be made with a precision of 10 microns, comparable to the size of a single cell body, according to the researchers. At the other end of the spectrum, the researchers are aiming to create a cubic millimeter of brain tissue with 100,000 cells and 900 million connections.
The researchers believe their work can have far-reaching ramifications for studying how brain cells interact with each other. In the longer-term, the researchers believe the work can help provide a better understanding of how to design tissue implants that could be used to replace damaged tissue in patients and to create patient-specific medications.
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