There were more than 11,000 people on the waiting list for organ transplant in Germany alone at the beginning of this year, although on the average hardly half as many transplants are performed. The aim of tissue engineering is to create organs in the laboratory for opening up new opportunities in this field. Unfortunately, researchers have still not been able to supply artificial tissue with nutrients because they do not have the necessary vascular system.

Five Fraunhofer-institutes joined forces in 2009 to come up with bio-compatible artificial blood vessels. It seemed practically impossible to build structures such as capillary vessels, that are so small and complex, especially the branches and spaces in between. But production engineering came to the rescue, because rapid prototyping makes it possible to build workpieces specifically according to any complex 3-D model.

Now, the Fraunhofer scientists are working on transferring this technology to a generation of tiny biomaterial structures by combining two different techniques: 3-D printing technology established in rapid prototyping and multi-photon polymerisation developed in polymer science.

Successful combination
A 3-D inkjet printer can generate 3-D solids from a wide variety of materials very quickly. It applies the material in layers of defined shape and these layers are chemically bonded by UV radiation. This already creates microstructures, but 3-D printing technology is still too imprecise for the fine structures of capillary vessels.

This is why the researchers combine this technology with two-photon polymerisation. Brief, intensive laser impulses impact the material and stimulate the molecules in a very small focus point so that cross-linking of the molecules occurs. The material becomes an elastic solid, due to the properties of the precursor molecules that have been adjusted by the chemists in the project team.  In this way highly precise, elastic structures are built according to a 3D building plan. 

Dr. Günter Tovar (right)  is the project manager at the Fraunhofer Institute for Interfacial Engineering andBiotechnology IGB based in Stuttgart.

When ink is an artificial vessel system
You have to have the right material to manufacture 3-dimensional elastic solids. This is the reason why the researchers came up with special inks, because printing technology itself calls for very specific properties. Blood vessels have to be flexible and elastic and interact with the natural tissue. Therefore, the synthetic tubes are bio-functionalised so that living body cells can dock onto them.

The scientists integrate modified biomolecules - such as heparin and anchor peptides - into the inside walls. They also develop inks made of hybrid materials that contain a mixture of synthetic polymers and biomolecules right from the beginning. 

The second step is where endothelial cells that form the innermost wall layer of each vessel in the body can attach themselves in the tube systems.  Tovar points out "the lining is important to make sure that the components of the blood do not stick, but are transported onwards."  The vessel can only work in the same fashion as its natural model to direct nutrients to their destination if we can establish an entire layer of living cells.

Opportunities for Medicine
The virtual simulation of the finished workpieces is just as significant for project success as the new materials and production techniques. Researchers have to precisely calculate the design of these structures and the course of the vascular systems to ensure optimum flow speeds while preventing back-ups.

The scientists at Fraunhofer are still at the dawn of this entirely new technology for designing elastic
3-D shaped biomaterials, although the technology offers a whole series of opportunities for further development.

Tovar acknowledges "We are establishing a basis for applying rapid prototyping to elastic and organic biomaterials. The vascular systems illustrate very dramatically what opportunities this technology has to offer, but that's definitely not the only thing possible."

"One example would be building up completely artificial organs based on a circulation system with blood vessels created in this fashion to supply them with nutrients. They are still not suited for transplantations, but the complex of organs can be used as a test system to replace animal experiments.

"It would also be conceivable to treat bypass patients with artificial vessels. In any event, it will take a long time until we will actually be able to implant organs from the laboratory with their own blood vessels."

This is a project in which the Fraunhofer Institutes for Applied Polymer Research IAP in Potsdam, Interfacial Engineering and Biotechnology IGB in Stuttgart, Laser Technology ILT in Aachen, Manufacturing Engineering and Automation IPA in Stuttgart,and Material Mechanics IWM in Freiburg, Germany are all participating and  exhibiting a large model of an artificial blood vessel printed with conventional rapid prototyping technologies and samples of their current developments in Hall 9, Stand D10 at the Biotechnica Fair.