Researchers at the Wyss Institute of Biologically Inspired Engineering at Harvard University has found a way to self-assemble complex structures out of gel “bricks” smaller than a grain of salt. The new method could help solve one of the major challenges in tissue engineering: creating injectable components that self-assemble into intricately structured, biocompatible scaffolds at an injury site to help regrow human tissues.
The key to self-assembly was developing the world’s first programmable glue. The glue is made of DNA, and it directs specific bricks of a water-filled gel to adhere only to each other.
“By using DNA glue to guide gel bricks to self-assemble, we’re creating sophisticated programmable architecture,” said Peng Yin, a core faculty member at the Wyss Institute and senior co-author of the study. Yin is also an assistant professor of systems biology at Harvard Medical School (HMS). This novel self-assembly method worked for gel cubes as tiny as a piece of silt (30 microns diameter) to as large as a grain of sand (1 millimeter diameter), underscoring the method’s versatility.
The programmable DNA glue could also be used with other materials to create a variety of small, self-assembling devices, including lenses and reconfigurable microchips as well as surgical glue that could knit together only the desired tissues, said Ali Khademhosseini, an associate faculty member at the Wyss Institute who is the other senior co-author of the study.
“It could work for anything where you’d want a programmable glue to induce assembly of higher-order structures, with great control over their final architecture — and that’s very exciting,” said Khademhosseini, who is also an associate professor at Harvard-MIT’s Division of Health Sciences and Technology, Brigham and Women’s Hospital, and Harvard Medical School.
To fabricate devices or their component parts, manufacturers often start with a single piece of material, then modify it until it has the desired properties. Other times they employ the practice used by auto manufacturers, making components with the desired properties, then assembling the components to produce the final device. Living organisms fabricate their tissues using a similar strategy, in which different types of cells assemble into functional building blocks that generate the appropriate tissue function. In the liver, for example, the functional building blocks are small tissue units called lobules. In muscle tissue, the functional building blocks are muscle fibers. Scientists have tried to mimic this manufacturing strategy by developing self-assembling systems to fabricate devices.
Peng Yin/The Wyss Institute – Gel bricks smaller than a grain of salt (top left) can be programmed to self-assemble into complex structures. The key is to attach a pair of connector cubes coated with matching DNA glue on the gel bricks that are meant to pair up.
Using DNA as programmable, sequence-specific ‘glues’, shape-controlled hydrogel units are self-assembled into prescribed structures. Here we report that aggregates are produced using hydrogel cubes with edge lengths ranging from 30 μm to 1 mm, demonstrating assembly across scales. In a simple one-pot agitation reaction, 25 dimers are constructed in parallel from 50 distinct hydrogel cube species, demonstrating highly multiplexed assembly. Using hydrogel cuboids displaying face-specific DNA glues, diverse structures are achieved in aqueous and in interfacial agitation systems. These include dimers, extended chains and open network structures in an aqueous system, and dimers, chains of fixed length, T-junctions and square shapes in the interfacial system, demonstrating the versatility of the assembly system.
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