Bioprinting Promises 3D Tissue Constructs with Multiple Cell Types and Blood Vessels

A promising and frankly incredible new bioprinting method seems to be having some success as it aims to create human tissue constructs realistic enough to test drug safety and effectiveness.

Background

Tissue engineers have tried for years to produce lab-grown vascularised human tissues robust enough to serve as replacements for damaged human tissue. Previous methods have yielded human tissue, but they have been limited to thin slices. When scientists try to print thicker layers of tissue, cells on the interior starve for oxygen and nutrients, and have no good way of removing carbon dioxide and other waste, leading to rapid tissue necrosis.

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard School of Engineering and Applied Sciences (SEAS) set out to mimic natural tissue’s blood supply, resorting to 3D printing methods that seem to be all over the news at the moment.

To print 3D tissue constructs with a predefined pattern, the researchers needed functional inks with useful biological properties, so they developed several “bio-inks” – tissue-friendly inks containing key ingredients of living tissues. One ink contained extracellular matrix, the biological material that knits cells into tissues. A second ink contained both extracellular matrix and living cells.

To create blood vessels, they developed a third ink with an unusual property: it melts as it is cools, rather than as it warms. This allowed the scientists to first print an interconnected network of filaments, then melt them by chilling the material and suction the liquid out to create a network of hollow tubes, or vessels.

The Harvard team then printed 3D tissue constructs with a variety of architectures, culminating in an intricately patterned construct containing blood vessels and three different types of cells – a structure approaching the complexity of solid tissues.

Perhaps the most exciting stage came when they injected human endothelial cells into the vascular network. It seems those cells regrew the blood-vessel lining, in so doing keeping cells alive and growing in the tissue construct.

The possibilities are endless for this technology if it proves out over the next few months. The initial focus is on creating functional 3D tissues that are realistic enough to screen drugs for safety and effectiveness, an area where it could have an immmediate impact.

But the holy grail for the technology would be if it could help to build fully functional replacements for injured or diseased tissue. Imagine if CAT scan data using computer-aided design (CAD), printed in 3D at the push of a button, could be used by surgeons to repair or replace damaged tissue.

Researcher comments

“This is the foundational step toward creating 3D living tissue,” said Jennifer Lewis, Ph.D., senior author of the study, who is a core faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University, and the Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard SEAS. Along with lead author David Kolesky, a graduate student in SEAS and the Wyss Institute, her team reported the results February 18 in the journal Advanced Materials.

“Tissue engineers have been waiting for a method like this,” said Don Ingber, M.D., Ph.D., Wyss Institute founding director. “The ability to form functional vascular networks in 3D tissues before they are implanted not only enables thicker tissues to be formed, it also raises the possibility of surgically connecting these networks to the natural vasculature to promote immediate perfusion of the implanted tissue, which should greatly increase their engraftment and survival”.

Source: Wyss Institute for Biologically Inspired Engineering at Harvard University

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