Tissue engineers experimenting with bioprinting techniques have found a way to 3D-print tissue constructs with multiple types of cells and tiny blood vessels, and by doing so have made a major step towards the goal of creating human tissue constructs realistic enough to test the effectiveness and safety of new drugs.

Harvard University's Wyss Institute for Biologically Inspired Engineering reports that the advancement could also be an important step toward building fully functional, bioprinted replacements for damaged or diseased tissue.

"This is the foundational step toward creating 3D living tissue," said the Wyss Institute's Jennifer Lewis, senior author of the research, which appears in the journal Advanced Materials.

Previous attempts at bioprinting functional tissue have fallen short because printing at too great a thickness would lead the cells in the tissue's interior to become starved of oxygen and nutrients. With no way to remove carbon dioxide and other waste, the tissue would suffocate and die.

Natural tissue is woven with a network of tiny, thin-walled blood vessels that deliver oxygen and remove waste, allowing our skin to be thicker and more functional than anything so far replicated in a lab.

This latest research centers around a variety of "bio-inks" that contain the essential ingredients of living tissues. One such bio-ink developed by the researchers to print blood vessels has the unusual characteristic of melting as it cools, rather than as it warms. This ink allowed the team to print an intricate network of filaments, then melt them by chilling the tissue and suctioning the melted liquid out, leaving hollowed-out blood vessels behind.

"They 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," Harvard's Wyss Institute reported in a news release. "Moreover, when they injected human endothelial cells into the vascular network, those cells regrew the blood-vessel lining. Keeping cells alive and growing in the tissue construct represents an important step toward printing human tissues."

Lewis said that the immediate potential impact of the work will be found in creating 3D-printed tissues that are realistic enough to screen drugs for safety and effectiveness. The material could also be of benefit to research on wound healing, blood vessel growth or tumor development.

"Tissue engineers have been waiting for a method like this," said Don Ingber, the 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."

The series of videos below shows the printing process. More information on this study can be found at https://wyss.harvard.edu