Blood vessels from a bioreactor

Whether it is the veins that carry deoxygenated blood to the heart, or the arteries that transport blood in pulse waves all the way from the heart to the tiniest blood vessels and supply the tissue with oxygen – clogged blood vessels cause problems. In the worst case scenario, a person whose arteries have become calcified may suffer a stroke or heart attack. Nearly 40 percent of all deaths in Germany were caused by such cardiovascular diseases in 2015. In the under-65 age group, they were even responsible for almost half of all deaths Europe-wide.

Bypasses save lives

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Bioartificial vascular prostheses could significantly reduce the risks following bypass operations.

If a patient is diagnosed with chronic atherosclerosis, a vascular bypass is the most common solution, especially if the arteries are affected. This involves implanting a section of artificial blood vessel directly next to the blocked vessel to reroute the blood flow. Such vascular prostheses are made of artificial fibres or tissue taken from the patient's veins.

The working groups led by the doctor and kidney expert Cornelia Blume and the electrical engineer Holger Blume at Leibniz University Hannover have developed a device that they hope will allow artificial vessels to be grown from biomaterials and the body's own cells. "Our bioreactor imitates the environment in which a blood vessel in the body grows. In other words, we generate a pulse wave just like in the arteries and control the pressure, supply of nutrients and the oxygen content", explains Cornelia Blume. The bioreactor uses sensors to continuously monitor the levels and automatically adjust them if necessary.

Artificial blood vessels could be produced in a two-stage process

The first step is to create a blood vessel model that is five centimetres long and has a diameter of between 0.8 and one centimetre. So that it can grow in the bioreactor, a 3D printer is used to produce a tubular scaffold made of biodegradable plastic. Its surface must have countless tiny bulges to which cells encased in gel are attached in a separate printing process. After two to three weeks of growth in the bioreactor, this results in a carpet of tissue.

Theoretically, a vascular bypass of this kind has many advantages for the patient: as it is populated with the patient's own cells in the bioreactor, rejection reactions are unlikely. And because the artificial scaffold gradually dissolves and is replaced by the body's own tissue following implantation, the replacement blood vessels promise to be almost as versatile and flexible as the original. This means that patients would no longer need to take coagulants after surgery. Currently, there is always a risk of renewed clogging due to the turbulence that occurs at the comparatively rigid artificial blood vessels.

Improving the bioreactor

Before the new transplants can undergo animal testing, however, a number of problems still need to be resolved: "The surface structure of the vascular prostheses must be very delicate. We are reaching the limits of what is technically possible with the 3D printers currently available", says Cornelia Blume. And that is not the only hurdle. The pressure of the nutritional fluid on the cells in the bioreactor has to be regulated even more precisely.

In the NIFE research association, the two Hanover-based working groups want to find solutions to these technical problems in the next few years. Their objective of more accurately replicating a human blood vessel will not be achieved in anything like the near future, however. This would require the implant not only to be populated with the endothelial cells that line the vascular walls, but also with three other cell types: muscle cells, the connective tissue cells that ensure elasticity, and the capillary cells that are responsible for blood circulation. "Constructing such a complex structure is a long-term goal", explains Cornelia Blume.

A vision for the future: replacement organs grown in the lab

When talk turns to the production of whole organs, the doctor is even more cautious. "The tissue in a kidney for example is far more complex and is made up of highly specialised cells. Although research has discovered to some extent how such a structure forms in the body, we do not know which signalling processes the structure is based on at the cellular level", says kidney expert Blume. For now, the notion that we could grow entire replacement organs in the lab and thus end our reliance on donor organs will remain but an exciting vision for the future.

 

Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE)

Founded ten years ago, NIFE pools expertise in biomedical engineering in and around Hanover, the Lower Saxony state capital. Under its umbrella, doctors, engineers and natural scientists from Hannover Medical School, Leibniz University Hannover, the University of Veterinary Medicine Hannover and the Laserzentrum Hannover collaborate in 34 working groups. Their goal is to develop artificial, semi-artificial and biological implants, including not only vascular implants but also heart valves and replacement tissue for oral and maxillofacial surgery. The NIFE scientists are for example also working on developing audio and neural prostheses that interact directly with the nerve cells, allowing a person's hearing to be restored completely rather than only in part. Their cooperation allows biomedical technologies to be rapidly transferred into clinical practice.

www.nife-hannover.de