The technology for 3D printing human tissue has improved over the years, but it’s still an extremely slow process. Part of this is due to how each cell needs to be arranged, as well as how easily they damage during printing. However, recent advancements have allowed researchers not only to 3D bioprint tissues ten times faster than existing procedures, but do so directly onto a wound for faster healing times.
A study published in Nature Communications by a team at Penn State lays out the key factor for speeding up tissue generation: tiny cell clusters known as spheroids. Unlike previous bioprinting options that lack the necessary, spheroids better approximate cell densities seen in the human body. Ibrahim Ozbolat, study co-author and professor of engineering science and mechanics, biomedical engineering, and neurosurgery, likens it to building a wall, with cells as the bricks and bioink as the mortar.
“This technique… enables the bioprinting of tissues in a high-throughput manner at a speed much faster than existing techniques with high cell viability,” Ozbolat said in a statement.
Ozbolat and colleagues previously invented an aspiration-assisted bioprinting system that used a pipette’s tip to lift, transfer, and position individual spheroids into a shape that fostered self-assembly and growth into solid tissue. But such an incremental process meant that it took engineers days to create one cubic centimeter of material.
Additional research and analysis has allowed Ozbolat’s team to subsequently develop what they call the High-throughput Integrated Tissue Fabrication System for Bioprinting (HITS-Bio). Instead of manual assembly, HITS-Bio employs a four-by-four array of pipette nozzles that are digitally directed to move in three dimensions, all while also handling multiple spheroids at once. The multinozzle tool can handle as many as 16 spheroids at a time, moving them into exact configurations in a bioink substrate. In this way, HITS-Bio can exponentially speed up 3D bioprinting cell structures.
“We can then build scalable structures very fast. It’s 10-times faster than existing techniques and maintains more than 90% high cell viability,” said Ozbolat.
Researchers undertook two separate tests to showcase the new technique’s abilities. In the first experiment, the team used HITS-Bio to make a one-cubic-centimeter block from about 600 spheroids of cells able to grow into cartilage. Instead of days of work HITS-Bio built its spheroid sample in less than 40 minutes.
[Related: Bioprinting breakthrough uses acoustic waves to create lab-grown human tissue.]
The technique already shows promise beyond the laboratory, too. In another experiment, Ozbolat and colleagues used HITS-Bio during surgery to spheroid-infused bioink directly into a wound located on a rat’s skull—a world first. With the help of microRNA technology to control gene expression, researchers steered the spheroids to grow into actual bone. Post-surgery, the wound was almost entirely healed in about six weeks.
“It actually sped up the bone repair,” Ozbolat said.
Researchers next want to work on scaling the HITS-Bio method to tackle more complex tissues, possibly through the addition of more nozzles. If they can figure out how to incorporate blood vessel cell printing—necessary for clinically and surgically viable transplant tissue—the team believes the technology may one day even help print entire organs such as livers.
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