Two researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering have developed a new technique to construct biological structures the size of a grain of sand with unprecedented precision, a discovery that could herald better construction of artificial tissues.

While biomedical researchers have been able to assemble structures on a nano-scale, constructing precise, medium-scale structures—those that are the size of a grain of sand—has long posed a significant challenge.

“People are really good at making things that are astonishingly small, but it’s really hard to do stuff in the middle,” said Casey N. Grun ’14, the project’s undergraduate research assistant. “It’s about trying to establish things in this meso-scale...which is a sweet spot.”

Meso-scale structures involve combinations of biocompatible hydrogel blocks: water-based biological substances that can be inserted in the human body without causing adverse effects. A downside to using gel blocks, however, has been combining them in the right order. Ali Khademhosseini and Peng Yin, two professors at the Harvard Medical School, tackled the problem with a technique they dubbed “DNA glue.”

“Think about glue in everyday—with everyday glue, you can more or less make any two objects stick together,” Yin said. “But with DNA glue, if we made some blocks blue and some blocks red, we could make the glue so that only the red color can stick the red color, [and] the blue color only sticks to the blue color.”

A strand of DNA consists of a sequence of nucleotides, and nucleotides can only combine in certain patterns. By coating gel blocks with specific DNA sequences, Khademhosseini and Yin were able to ensure that the blocks connected correctly.

Grun worked in Peng’s lab with a software that allowed him to design the sequences of DNA that bound the blocks together. He had to ensure that the “DNA glue” only attached to other DNA. “It is a challenging problem because it’s not immediately obvious how to design long sequences of DNA that don’t bind spuriously with other things,” said Grun.

Khademhosseini and Yin said they hope further research could apply this new technique in medical procedures, such as the treatment of damaged human tissues.

They detailed their process in the Sept. 9, online issue of Nature Communications, and Khademhosseini described the improvements that this technique could facilitate in artificial tissue development and implementation in an email to The Crimson.

“By using these gels that can be self-assembled with DNA glue, we can aim to recreate such architectures to better enable the formation of engineered tissues,” Khademhosseini wrote. “Of course, this is far away still but [it is] one way that we can try to go about engineering artificial tissues.”

—Staff writer Sonali Y. Salgado can be reached sonali.salgado@thecrimson.com. Follow her on Twitter @SonaliSalgado16.