Vascularized tissues were obtained by a new 3D printing method
An important step on the way to printing living tissues
NanoNewsNet based on the materials of the Wyss Institute: An Essential Step towards Printing Living TissuesA new bioprinting method developed by scientists at the Wyss Institute for Biologically Inspired Engineering of Harvard University and the Harvard School of Engineering and Applied Sciences allows you to create complex three-dimensional tissue structures from several types of cells with the smallest blood vessels.
This work represents an important step towards the long–standing goal of tissue engineers - to create structures from human tissues that are realistic enough to test the safety and effectiveness of medicines on them.
In addition, the development of this method is the first but important step towards creating fully functional structures that surgeons can use to replace or repair damaged or diseased tissues. With the help of a computer-aided design system, based on computed tomography data, such three-dimensional structures can be created by simply pressing the button of a 3D printer.
"This is a fundamental step towards creating three–dimensional living tissues," says study leader Jennifer Lewis, PhD. Together with lead author David Kolesky, her group published their results in the journal Advanced Materials (Kolesky et al., 3D Bioprinting of Vascularized, Heterogenic Cell-Laden Tissue Constructs).
In a new 3D printing method developed by Jennifer Lewis and her group,
several print heads and special inks are used.
(Photo: Wyss Institute and Harvard School of Engineering and Applied Sciences)
Tissue engineers have been trying for many years to create vascularized human tissues that are reliable enough to serve as a replacement for damaged tissues of a living organism. Human tissues have been printed before, but their samples are no more than a third of a dime thick. In structures of greater thickness, cells located deep in the tissue suffer from a lack of nutrients and oxygen and are unable to remove carbon monoxide and other toxic metabolic products. They suffocate and die.
Nature solves this problem by providing tissues with a network of tiny thin-walled blood vessels that feed cells and remove waste, and Koleski and Lewis decided to imitate this most important invention of hers.
3D printing does an excellent job of creating finely detailed three-dimensional structures, usually made of inert materials such as plastics or metals. Dr. Lewis and her group are pioneers in developing a wide range of new inks that harden into materials with useful electrical and mechanical properties. Such inks allow 3D printing to move from reproducing a form to reproducing the inherent function of that form.
In the human body, a network of small blood vessels nourishes the tissue and removes waste. Jennifer Lewis and her colleagues have developed a 3D printing method for tissue structures that allows creating a single structure of several types of cells "glued" into the tissue by an extracellular matrix, with a vascular network embedded in it. (Photo: Wyss Institute for Biologically Inspired Engineering at Harvard University)To print three-dimensional fabric structures with a given structure, the researchers needed functional ink with useful biological properties, and they developed several bio-ink containing key ingredients of living tissues.
Some ink contained an extracellular matrix, a biological material that binds cells into tissue. The second ink contained both extracellular matrix and living cells. To create blood vessels, researchers have developed a third ink with an unusual property: it melts when cooled, not when heated. By printing a network of threads, melting them by cooling the material and removing the resulting liquid, they obtained a network of hollow tubes simulating vessels.
To evaluate the possibilities and versatility of their method, the scientists printed three-dimensional fabric structures with different architectures. The culmination was a complex structure containing blood vessels and three different types of cells. In terms of complexity, such a structure approaches solid tissues of higher organisms.
Moreover, human endothelial cells introduced into the vascular network formed the lining of blood vessels. What Lewis and her colleagues have achieved – the ability to support the life and growth of cells in such a tissue structure – is an important step towards printing human tissues.
"Ideally, we want biology itself to do the most work," comments Dr. Lewis.
Currently, Lewis and her group are creating functional 3D tissues suitable for drug screening, but by working with printed tissue structures, scientists can already shed light on the fundamental processes occurring in living tissues with complex architecture – wound healing, blood vessel growth, tumor development, and stem cell interaction with their niches.
"Tissue engineers have been waiting for such a method to appear for a long time," says Don Ingber, MD, founding director of the Wyss Institute. "The ability to form functional vascular networks in 3D tissues before their implantation not only makes it possible to create tissues of greater thickness, but also opens up the prospect of surgical connection of these networks to natural vasculature, which, providing immediate perfusion of the implanted tissue, will significantly increase its engraftment and survival."
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