The 4D hydrogel-based material changes shape in response to water. In the image, the grey side of the material absorbs water faster than the blue side, causing it to bend into a 'C' shape. Image: Yu Bin Lee.
The 4D hydrogel-based material changes shape in response to water. In the image, the grey side of the material absorbs water faster than the blue side, causing it to bend into a 'C' shape. Image: Yu Bin Lee.

New hydrogel-based materials that can change shape in response to physiological stimuli, such as water, could provide the next generation of materials for bioengineering tissues and organs, according to a team of researchers at the University of Illinois, Chicago (UIC).

In a new paper in Advanced Functional Materials, the research team that developed the substances, led by Eben Alsberg, professor of biomedical engineering, reports that the unique materials can curl into tubes in response to water, making them good candidates for bioengineering blood vessels or other tubular structures.

In nature, embryonic development and tissue healing often involve a high concentration of cells and complex architectural and organizational changes that ultimately give rise to final tissue morphology and structure.

In tissue engineering, biodegradable polymer scaffolds are often cultured with cells in biochambers filled with liquid nutrients that keep the cells alive. Over time, when provided with appropriate signals, the cells multiply in number and produce new tissues that take on the shape of the scaffold as it degrades. For example, a scaffold in the shape of an ear seeded with cells capable of producing cartilage and skin tissue may eventually become a transplantable ear.

However, a geometrically static scaffold cannot grow tissues that dynamically change shape over time or facilitate interactions with neighboring tissues that change shape. A high density of cells is also typically not used and/or supported by the scaffolds.

"Using a high density of cells can be advantageous in tissue engineering as this enables increased cell-cell interactions that can promote tissue development," said Alsberg, who is also professor of orthopaedics, pharmacology and mechanical and industrial engineering at UIC.

Enter 4D materials, which are like 3D materials but change shape when exposed to specific environmental cues, such as light or water. These materials have been eyed by biomedical engineers as potential new structural substrates for tissue engineering, but most currently available 4D materials are not biodegradable or compatible with cells.

To take advantage of the promise of 4D materials for bioengineering applications, Alsberg and his colleagues developed novel 4D materials made from gelatin-like hydrogels that change shape over time in response to the addition of water. These hydrogels are also cell-compatible and biodegradable, making them excellent candidates for advanced tissue engineering. In addition, they support very high cell densities, so can be heavily seeded with cells.

In the paper, the researchers describe how exposure to water causes the hydrogel scaffolds to swell as the water is absorbed. The amount of swelling can be tuned by, for example, altering aspects of the hydrogel material such as its degradation rate or the concentration of cross-linked polymers – strands of protein or polysaccharide in this case – that make up the hydrogels. The higher the polymer concentration and crosslinking, the less and more slowly a given hydrogel will absorb water to induce a change in shape.

The researchers found that when they formed stacks of hydrogel layers with different properties, the difference in water absorption between the layers will cause the stack to bend into a 'C'-shaped conformation. If the stack bends enough, a tubular shape is formed, which resembles structures like blood vessels and other tubular organs.

By calibrating the system, the researchers found they could control the timing and the extent of the shape change. They could also embed bone marrow stem cells into the hydrogel at very high density – the highest density of cells ever recorded for 4D materials – and keep them alive, a significant advance in bioengineering that has practical applications.

In the paper, the researchers describe how their shape-changing, cell-laden hydrogel could be induced to become bone- and cartilage-like tissues. By implementing 4D bioprinting of this hydrogel, they could also obtain unique configurations to achieve more complex 4D architectures.

"Using our bilayer hydrogels, we can not only control how much bending the material undergoes and its temporal progression, but because the hydrogels can support high cell densities, they more closely mimic how many tissues form or heal naturally," said Yu Bin Lee, a biomedical engineering postdoctoral researcher and first author of the paper. "This system holds promise for tissue engineering, but may also be used to study the biological processes involved in early development."

This story is adapted from material from the University of Illinois, Chicago, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.