Scientists bioprint tissue-like structures capable of controlled complex shape changes University of Illinois at Chicago bioprinted cell-rich biological structures showing controlled, complex 4D shape transitions. Image credit: Eben Alsberg and Aixiang DingStandard 3D printing uses digital blueprints to create objects from materials such as plastic or resin, while 3D bioprinting uses living cells or bioink to create biological parts and tissues. A fourth dimension - shape transformation over time - can be achieved by combining materials that allow printed structures to deform multiple times in response to external signals in a pre-programmed or on-demand manner. Bioprinted 4D constructs offer scientists the opportunity to better mimic the shape changes that occur during the development, healing and normal function of real tissues and to fabricate complex structures.

A new study in the scientific journal Advanced Materials describes the development of a new cell-laden bioink consisting of tightly packed sheets of microgels and live cells for bioprinting 4D structures. The new system is capable of producing cell-rich biological structures that can change shape under physiological conditions.

The study, "Clogged Microsheet Hydrogels for Four-Dimensional Live Cell Bioprinting," was authored by engineers at the University of Illinois at Chicago who created bioinks and conducted experiments with prototype hydrogels.

Their experiments yielded a variety of complex biological structures with well-defined configurations and high cell viability, including 4D cartilage-like tissue formation. Further designs demonstrated complex, multiple 3D-to-3D shape transitions in biological constructs fabricated in a single print.

"This bioink system offers the opportunity to print biological structures that are capable of achieving more complex structural changes over time than previously possible. With pre-programmable and controlled shape deformation, these cell-rich structures promise to better mimic the natural developmental processes of the human body and could help scientists make more accurate studies of tissue morphogenesis and greater advances in tissue engineering," study corresponding author Eben Alsberg, Richard and Loan Hill, chair who holds positions in biomedical engineering, mechanical and industrial engineering, pharmacology and regenerative medicine, and orthopedics, said.

Alsberg said the bioink advances prior technology in a number of ways.

"This bioink has so-called shear thinning and fast self-healing properties that allow smooth extrusion-based printing with high resolution and high fidelity without a support bath. The printed biological structures are further stabilized by light-based cross-linking while remaining intact - for example - bending, twisting or undergoing any number of multiple deformations. With this system, it is possible to bioengineer cartilage-like tissues with complex shapes that evolve over time," Alsberg said. "Another key achievement is the design of a system that is capable of fabricating biological structures capable of complex 3D-to-3D shape transformations."

"This is the first system to meet the demanding requirements of bioprinting 4D structures: loading live cells in bioink, being able to print large complex structures, triggering shape transformation under physiological conditions, supporting long-term cell viability and promoting desired cellular functions such as tissue regeneration," UIC postdoctoral fellow and first author of the paper Aixiang Ding said. "We are working to translate the system into clinical applications for tissue engineering because of the severe shortage of available donor tissues and organs."

UIC's Oju Jeon, David Cleveland, Kaelyn Gasvoda, Derrick Wells and Sang Jin Lee are co-authors of the paper.

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