Researchers develop first voxel building blocks for 3D-printed organs

A research team at the University of Virginia School of Engineering and Applied Science has developed a template for the first voxel building blocks that could be printed on demand.

Led by Liheng Cai, assistant professor of materials science and chemical engineering, and his graduate student Jinchang Zhu, a biomaterial has been developed with mechanical properties similar to various human tissues. This development could represent an important step towards the production of human-compatible organs on demand.

In the study published on Saturday in the journal Nature Communications, Cai and Zhu present their innovative bioprinting method, known as digital assembly of spherical particles (DASP). This technique uses water-based particles of biomaterials deposited in a support matrix to build 3D structures that provide a suitable environment for cell growth. The method uses so-called “voxels”, the 3D equivalent of pixels, to construct objects.

“Our new hydrogel particles represent the first functional voxel we have ever made,” Zhu said. “With precise control over mechanical properties, this voxel may serve as one of the basic building blocks for our future printing constructs. “For example, with this level of control, we could print organoids, which are 3D cell-based models that function as human tissue, to study disease progression in the search for cures.”

The particles consist of polymer hydrogels that mimic human tissue by modifying the arrangement and chemical bonds of individual monomers. Real human cells are enclosed within the particles. Compared to other hydrogel bio-inks, the materials developed by Cai and Zhu are less toxic and more biocompatible. Their “double network” hydrogels, which consist of two interwoven molecular networks, are mechanically strong and highly adaptable to mimic the physical properties of human tissue.

Cai and Zhu first presented their DASP technology in 2021 in the journal Advanced Functional Materials. This work proved the concept of using biomaterial voxels as building blocks and demonstrated through laboratory experiments a DASP-printed material that functioned like a pancreas and responded to glucose with insulin release.

In their latest publication in Nature Communications, Cai and Zhu present DASP 2.0, which introduces an improved hydrogel bio-ink with a “click chemistry” process to rapidly crosslink the molecular structures. Part of this advancement was also the improvement of the team’s bioprinter. They developed a multi-channel nozzle that mixes the hydrogel components on demand as cross-linking is very fast, going from liquid droplets to an elastic, water-filled gel within 60 seconds.

DASP achieves the required replication of mechanical properties by depositing large droplets from a narrow, fast-moving nozzle into the matrix, where they are immediately suspended.

“Precise manipulation of viscoelastic voxels represents both a fundamental and technological challenge in soft matter science and 3D bioprinting,” Cai said in 2022, when they published their second paper on DASP. “We’ve now laid the foundation for voxelated bioprinting,” he said. “When fully realized, DASP’s applications will include artificial organ transplant, disease and tissue modeling, and screening candidates for new drugs. And it probably won’t stop there.”

The research was funded by the National Science Foundation and several other institutions.