UIC engineers develop a new 4D platform to create artificial tissues

Engineers at the University of Illinois Chicago have developed a new bioprinting platform for creating artificial tissues. The materials made by this technology, which consist of living cells and polymers and can change shape using the cells' own forces, could allow researchers to engineer implants that more realistically replicate body tissues.

Researchers can use bioprinting to make three-dimensional structures like blood vessels, cartilage and bones. They can make these static structures "four-dimensional" by exposing them to stimuli like heat or light that cause them to change their shape over time. The new platform, however, doesn't require an external stimulus. It uses cell-generated forces to morph the bioprinted constructs into complex shapes.

"In other traditional systems, an external stimulus like light, heat, electricity or a magnetic field is used. In our system, we use a different strategy. We utilize an internal, intrinsic stimulus derived from the cells within the constructs," said Aixiang Ding, research assistant professor of biomedical engineering at UIC. Ding and coauthors recently published a paper on the new 4D bioprinting in the journal Matter.

In the body, tissues change their shape over time when they grow and heal. It would be valuable, the researchers said, to create tissue implants that can morph, regenerate and otherwise behave like natural tissues without needing additional external stimuli or signals. It could be challenging to, for example, shine light on a structure inside the body to get a tissue implant to change shape, Ding explained.

One of the researchers' goals is to establish a system that can emulate the dynamic movements of tissue that are observed in vivo, said Kaelyn L. Gasvoda, who worked on the project as a PhD candidate at UIC and is now a postdoctoral research fellow at the Mayo Clinic. "We want to be able to apply this for healing complex defect areas like airways and joints."

The team, led by Eben Alsberg, the Richard and Loan Hill Chair and Distinguished Professor in the College of Engineering, has been pioneering novel approaches for 4D bioprinting for several years and creating biomaterials that can morph in response to external stimuli. However, external stimuli can be difficult to apply in the body or may alter cell or tissue behavior, said Ding. For this reason, the researchers wanted to explore a natural cell behavior: cell contractile forces, the mechanical forces a cell generates when it uses its internal infrastructure to move, change shape and form tissues.

"This study centers around the innovation of using a normally occurring cell process, force generation, to drive the formation of tissue curvature," said Gasvoda.

In previous studies, Alsberg's team developed 4D materials that can form complex curvatures. They added stem cells to these materials and made sure they could stay alive within them, then tested how well the cells could produce different tissue types like bone and cartilage while changing shape.

"Our goal isn't just to create some tissue curvatures while maintaining cell viability," said Gasvoda. "We want to also produce functional tissues that can be used for therapeutic regeneration applications."

In the current study, to test the bioink's ability to make different shapes, the researchers printed the bioink into centimeters-long structures and then transferred these structures to tissue-culturing devices. They arranged layers of bioink containing cells and layers of bioink without cells into specific patterns. The layer with the cells contracted or shrunk due to the contractile forces, causing entire structures to curve in a pre-designed direction.

"Through careful design of the system parameters, it is possible to engineer bending, twisting or curling transformations to form complex shapes," said Ding. "With specifically designed patterns, we can program the shape change." The team created tubes, U-shapes, S-shapes, spirals and arc-like constructs with the 4D platform.

While shape changes can happen faster with external stimuli (structures made with this new 4D technology usually take a few days to form), harnessing cell contractile forces more accurately mimics a natural mechanism the body uses during development, the researchers said. They have not tested it in a living system yet, but the potential is promising.

"This could potentially be used for modeling the curvature of a gland because we are able to achieve such intricate curvatures within our constructs here. Alternatively, we could use this for the formation of a native blood vessel because we're able to create tubular shapes similar to a native blood vessel," said Gasvoda.

Ding, Gasvoda and David Cleveland share co-first authorship on the paper.