September 29, 2021
Israeli Breakthrough: Printing Blood Vessel Networks For Implantation
Printing Blood Vessel Networks for Implantation L-R Dr. Ariel Alejandro Szklanny and Professor Shulamit Levenberg / Technion

For the first time, Technion scientists succeeded in constructing a network of major and small blood arteries, crucial for giving blood to implanted tissue

Researchers lead by Technion Professor Shulamit Levenberg, who specialises in tissue engineering, have succeeded in establishing a hierarchical blood artery network, crucial for giving blood to implanted tissue. In the research published in Advanced Materials, Dr. Ariel Alejandro Szklanny employed 3D printing for constructing huge and small blood arteries to form for the first time a system that comprised a functioning combination of both. The breakthrough took accomplished in Prof. Levenberg’s Stem Cell and Tissue Engineering Laboratory in the Technion’s Faculty of Biomedical Engineering.

The heart pumps blood into the aorta, which branches out into progressively smaller blood arteries, bringing oxygen and nutrients to all the tissues and organs. Transplanted tissues, as well as tissues created for transplantation, require similar blood vascular support.

Printing Blood Vessel Networks for Implantation

Previous experiments with synthetic tissue containing hierarchical vessel networks have involved an intermediary step of transplanting first into a healthy limb, enabling it to be infiltrated by the host’s blood vessels, and then transferring the structure into the damaged location.

Notably, whereas prior studies employed animal collagen to create the scaffolds, the Israeli company CollPlant modified tobacco plants to make human collagen, which was successfully used for 3D bioprinting the vascularized tissue structures.

This study is a significant step forward in the direction of individualized medicine. Large blood vessels with the precise shape required can be manufactured and inserted alongside the tissue to be implanted. This tissue can be created using the patient’s own cells, hence avoiding the possibility of rejection.

Notably, whereas prior studies employed animal collagen to create the scaffolds, the Israeli company CollPlant modified tobacco plants to make human collagen, which was successfully used for 3D bioprinting the vascularized tissue structures.

This study is a significant step forward in the direction of individualized medicine. Large blood vessels with the precise shape required can be manufactured and inserted alongside the tissue to be implanted. This tissue can be created using the patient’s own cells, hence avoiding the possibility of rejection.

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The future of personalised medicine: Technion team built blood tree from scratch

Currently, transplanted grafts need to be implanted into a healthy part of the body so that the patient can generate new blood vessels to support it.

Engineered blood vessels in Technion study. Vascular structures in the scaffold lumen (brown) communicate with vessels located in the surrounding hydrogel (green).
(photo credit: Courtesy)

Skin flaps, bone grafts, implanted tissue – recent advancements in medicine have changed the face of surgery in terms of autologous – meaning self – transplantations.

While extensive damage to organs once meant a nearly sure amputation or need for an external transplant, today’s science focuses on harvesting cells and tissue from a person’s own body to complete the injured pieces of the puzzle, using grafts and flaps to repair skin, vessels, tubes and bones.

Yet, ask any surgeon attempting to insert a flap and they would tell you that the most important – and restrictive – component of a graft’s success is ample blood supply.

A team of researchers at the Technion recently found a way to meet this need. For the first time, these scientists succeeded in 3D printing a network of big and small blood vessels that could provide blood to implanted tissues just like the human body.

Up until now, medicine hasn’t been able to mimic the body’s ability to create a suitable hierarchy in the blood vessel tree. In our bodies, the heart pumps blood into a large tube called the aorta, which measures roughly 2-3 cm in diameter. The blood vessels then branch off into smaller and smaller tubes that are appropriate to each organ’s need and capacity, until they reach minuscule arterioles of only 5 to 10 micrometers.

HUMAN BODY circulatory system showing the heart and blood vessels (credit: FLICKR)

Dr. Ariel Alejandro Szklanny of the Technion team, led by Professor Shulamit Levenberg, a specialist in tissue engineering, found a way to use 3D printing to form a system containing a functional combination of both the large and small vessels.

The new breakthrough may allow a tissue flap to be created in a lab already connected to a blood network suited to its size and function.

Currently, transplanted grafts need to be implanted into a healthy part of the body so that the patient can generate new blood vessels to support it; then, the graft is relocated to an affected area as healthy tissue.

The new technique could potentially eradicate this intermediate step, drastically improving recovery times and cutting down on the number of procedures a patient would need to undergo.

In his recently published study in Advanced Materials, Dr. Szklanny described how he created a polymeric scaffold filled with small holes, mimicking the large blood vessels of the body. These holes allowed the connection of smaller vessels to join into the engineered large vessels. With collagen bio-ink, the team then printed and assembled a complex network around and within the main scaffold, later covering it with endothelial (human blood vessel lining) cells. A week later, the incubated artificial apparatus joined with the cells to create a hierarchical structure just like the human blood vessel tree. 

While previous studies in this field used animal-borne collagen, the Technion team used engineered tobacco plants created by the Israeli company CollPlant.

The mesh was transplanted into a study rat and attached to the main artery in its leg. The blood through the artery spread through the network exactly as it would within the body, carrying oxygen and nutrients to the distant parts of the implanted tissue, and without any leaks.

This achievement is an important tool in the world of personalized medicine and could be a huge leap forward in tissue engineering and treatment.

 

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