3Rs-Centre Utrecht Life Sciences

Faculteit Dierengeneeskunde
 
April 2017
3Rs in development of microsurgery techniques at Elana

This month, the 3Rs-Centre ULS visited Elana bv. This company develops and manufactures medical devices for bypass surgery. Their product is based on the invention of Prof. C. Tulleken and his research team, at the department of Neurosurgery at the University Medical Centre Utrecht (UMCU). The innovative technique is developed almost entirely without the use of laboratory animals. Saskia Redegeld is the research and lab manager at Elana. She has been working here since 2009. The company was founded in 2004.

ELANA (Excimer Laser Assisted Non Occlusive Anastomosis) is an exceedingly refined suture technique. It provides a solution for a selection of patients with vascular diseases that have no other options left but to get a bypass in the brain. A unique feature of the ELANA technique is that there is no temporary occlusion of the blood-flow during the surgery. This can significantly diminish the risk of stroke in the patient. A detailed illustration of the bypass technique is found in this video.

Waking up bright and early for biomaterials
Almost everything Saskia and her colleagues do in the lab to refine the ELANA technique is done ex vivo. They use biomaterials, which they obtain at the slaughter house. For example, a lot of their research is performed on rabbit arteries. The rabbit aorta strongly resembles human cranial vessels. Moreover, rabbit blood vessels are not used for consumption and are therefore considered as waste products in the food industry. For the development of a specific technique at Elana bv, the aorta is isolated from the rabbit cadaver. The thoracic tissue of the aorta is then used as the donor in the procedure, the abdomen tissue is used as the receiver. Redegeld: “When we need new rabbit cadavers, we have to get up very early in order to collect them at the slaughter house. However, this is quite rewarding since in return we do not have to sacrifice any animals for our research.”

The catheter used in the technique is tested in 18 different configurations, in order to establish which one is the best. After that, the catheter is tested together with an Elana clip (which is an updated version of the ring in the video). The tests are performed on rabbit aorta’s, which are kept under pressure. This facilitates the performance of many tests. Only after the best catheter-clip combination is found, which could be after something between 100 or 1000 tests, the procedure is tested in living rabbits. The added value of this in vivo test is the influence of  blood instead of water during the procedure. These experiments are terminal, and aim to study side-effects like back-wall damage in the artery. If these procedures have succeeded, the technique is tested in a long-term experiment in pigs. These studies are still necessary to investigate the development of the bypass over time.


Optimizing the ELANA technique on a rabbit aorta.

The Dura project
Another project that is executed at Elana bv is the dura project. This project aims to develop a sealant, that can be used to close the dura, the thick mesodermal membrane that surrounds the brain and spinal cord, and block the passage of fluids after surgery. In this project, dura tissue is again obtained from the slaughter house. The tissue is used to test and evaluate burst pressure of newly developed glue products. “Normally, these products are tested on intestinal membrane, but that has a structure quite different from the dura,” explains Redegeld. After two years of research in the lab, the project has now proceeded to a study in pigs. For the sake of refinement, the pigs are placed in hammocks after surgery. This prevents them from hurting themselves while they recover from the surgical procedure.
All in all, Elana shows that many steps towards the development of high quality medical innovations can be achieved without sacrificing animals. This may serve as an inspiration to others in this field.



Experimental setting at the Dura project: Under the red cones, sealant products are evaluated on burst pressure. Picture taken by Saskia Redegeld.



If you would like to read more on research performed at Elana, we recommend the following articles:

  • Thines, L., Proust, F., Marinho, P., Durand, A., van der Zwan, A., Regli, L., & Lejeune, J. P. (2016). Giant and complex aneurysms treatment with preservation of flow via bypass techniqueNeurochirurgie, 62(1), 1-13.

  • Bremmer, J., van Doormaal, T. P., Verweij, B. H., van der Zwan, A., Tulleken, C. A., & Verdaasdonk, R. (2016). Vessel wall perforation mechanism of the excimer laser-assisted non-occlusive anastomosis techniqueLasers in medical science, 31(6), 1169-1175.