For the first time, Technion scientists succeeded in forming a network of big and small blood vessels, necessary for supplying blood to implanted tissue.

Researchers led by Technion Professor Shulamit Levenberg, who specialises in tissue engineering, have succeeded in creating a hierarchical blood vessel network, necessary for supplying blood to implanted tissue. In the study, recently published in Advanced Materials, Dr. Ariel Alejandro Szklanny used 3D printing for creating big and small blood vessels to form for the first time a system that contained a functional combination of both. The breakthrough took place in Prof. Levenberg’s Stem Cell and Tissue Engineering Laboratory in the Technion’s Faculty of Biomedical Engineering.

In the human body, the heart pumps blood into the aorta, which then branches out into progressively smaller blood vessels, transporting oxygen and nutrients to all the tissues and organs. Transplanted tissues need similar support of blood vessels, and consequently so do tissues engineered for transplantation. Until now, experiments with engineered tissue containing hierarchical vessel networks have involved an intermediary step of transplanting first into a healthy limb, allowing the tissue to be permeated by the host’s blood vessels, and then transplanting the structure into the affected area. (e.g. this study by Idan Redenski about engineered bone grafts, published earlier this year.) With Dr. Szklanny’s new achievement, the intermediary step might become unnecessary.

To create in the lab a tissue flap with all the vessels necessary for blood supply, Dr. Szklanny combined and expanded on two separate techniques. First, he created a fenestrated polymeric scaffold that mimics the large blood vessel, using 3D printing technologies. The fenestration served to create not just a hollow tube, but a tube with side openings that allowed the connection of smaller vessels to the engineered larger vessel. Using a collagen bio-ink, tissue was then printed and assembled around that scaffold, and a network of tiny blood vessels formed within. Finally, the large vessel scaffold was covered with endothelial cells, which are the type of cells that constitute the inner layer of all blood vessels in the body. After a week of incubation, the artificial endothelium created a functional connection with the smaller 3D bio-printed vessels, mimicking the hierarchical structure of the human blood vessel tree.

The resulting structure was then implanted in a rat, attached to its femoral artery. Blood flowing through it did what we would want blood to do: it spread through the vessel network, reaching to the ends of the structure, and supplied blood to the tissue without leaking from the blood vessels.

One interesting point to note is that while previous studies used collagen from animals to form the scaffolds, here, tobacco plants were engineered by the Israeli company CollPlant to produce human collagen, which was successfully used for 3D bioprinting the vascularized tissue constructs.

This study constitutes an important step towards personalized medicine. Large blood vessels of the exact shape necessary can be printed and implanted together with the tissue that needs to be implanted. This tissue can be formed using the patient’s own cells, eliminating rejection risk.

The study received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme.

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