Scaling up tissue engineering with a new bioprinting technique

Bioprinting technique creates thick 3D tissues composed of human stem cells and embedded vasculature, with potential applications in drug testing and regenerative medicine

A team at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School for Engineering and Applied Sciences (SEAS) has invented a method for 3D bioprinting thick vascularized tissue constructs composed of human stem cells, extracellular matrix, and circulatory channels lined with endothelial blood vessel cells. The resulting network of vasculature contained within these deep tissues enables fluids, nutrients and cell growth factors to be controllably perfused uniformly throughout the tissue. The advance is reported March 7 in the journal Proceedings of the National Academy of Sciences.

“This latest work extends the capabilities of our multi-material bioprinting platform to thick human tissues, bringing us one step closer to creating architectures for tissue repair and regeneration,” says Wyss Core Faculty member Jennifer A. Lewis, Sc.D., senior author on the study, who is also the Hansörg Wyss Professor of Biologically Inspired Engineering at SEAS.

To date, scaling up human tissues built of a variety of cell types has been limited by a lack of robust methods for embedding life-sustaining vascular networks. Building on their earlier work, Lewis and her team have now increased the tissue thickness threshold by nearly tenfold, setting the stage for future advances in tissue engineering and repair. The method combines vascular plumbing with living cells and an extracellular matrix, enabling the structures to function as living tissues. In the study, Lewis and her team showed that their 3D bioprinted tissues could sustain and function as living tissue architectures for upwards of six weeks.

In the study, Lewis’ team demonstrated the 3D printing of one centimeter-thick tissue containing human bone marrow stem cells surrounded by connective tissue. By pumping bone growth factors through the supporting vasculature lined with the same endothelial cells found in our blood vessels, the team induced cell development toward bone cells over the course of one month.

“This research will help to establish the fundamental scientific understanding required for bioprinting of vascularized living tissues,” Zhijian Pei, National Science Foundation Program Director for the Directorate for Engineering Division of Civil, Mechanical and Manufacturing Innovation, which funded the project. “Research such as this enables broader use of 3-D human tissues for drug safety and toxicity screening and, ultimately, for tissue repair and regeneration.”

Learn more: Scaling up tissue engineering

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