Call to bring tissue-engineered grafts from “bench to bedside”

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The promise of autologous vascular prostheses justifies great efforts to transfer them “from the bench to the bedside”, according to Stefan Jockenhoevel of the Universitaetsklinikum Aachen, Germany.

The vascular field is looking to tissue engineering to improve on the low patency rate of small-calibre synthetic grafts.


“The aim of vascular tissue engineering is the production of a vascular graft which is autologous, as much as possible, has complete immunological integrity, has a viable, functionally active endothelial cell layer, with mechanisms of remodelling and self-repair, and with high resistance against infection,” said Jockenhoevel, speaking at the European Vascular Course, Maastricht, in February.


But, he said, production times and costs are currently prohibitive.


He described a few of the techniques currently being explored by researchers, including the unusual scaffold-free approach being pioneered by Nicolas L’Heureux and his team at Université Laval, Canada, in which layers of cells are cultivated and rolled up. Grafts developed in this way can withstand a burst pressure of more than 3,000mmHg.

 

“This approach has one major disadvantage,” said Jockenhoevel, “and that is that production time is around six to eight months to get one nice graft.”


Jockenhoevel’s own team in Aachen took a different approach: “We started with the hypothesis that successful tissue engineering has to mimic the process of tissue regeneration. And tissue regeneration is closely connected to haemostasis, as we see every day in the operating room.


“Fibrin, as the main protein of haemostasis, seems to provide a physiological substrate for tissue regeneration and therefore also for tissue engineering.” And, fibrin gel, he said, has proved an effective material for a scaffold on which to cultivate cells.


He admitted, however, that they allowed themselves a compromise on the goal of a completely autologous graft in order to reduce production time.


The race between these and other techniques for the production of bioactive grafts is still ongoing. “We don’t know which of them will be the best in clinical application,” he said. “The problem is that the production and the logistics are expensive and not yet suitable for daily use.”


Indeed, he said that the cost of a tissue-engineered graft is currently around €20,000-30,000.


“Nonetheless,” he added, “tissue-engineered grafts could be useful in particular applications; as small calibre grafts in difficult cases, dialysis shunt and cases of vasculitides.


“What we need,” he told delegates, “is people like you; surgeons with ideas to help to bring this concept forward.”

Papers from the European Vascular Course are published by Edizioni Minerva Medica.

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