In patients with end-stage renal disease treated by hemodialysis, the veins and arteries, into which needles are inserted several times per week, end up being irreparably damaged. They then need to be replaced. But current prostheses are not accepted by the body over the long term. Nicolas L’Heureux, Inserm Research Director, is therefore working on new artificial blood vessels, which are woven and contain no polyester.
What is the objective of the project for which you received a European Research Council (ERC) Advanced Grant?
The objective is to produce a new artificial blood vessel model which, unlike those currently available, contains no polyester. When we replace a vein or an artery, the substitute must immediately be able to resist blood pressure. That is why, unlike skin grafts, the current prostheses cannot be obtained by simply cultivating cells and reinforcing their cohesion with collagen gel: although it is a natural product, it is denatured during the preparation stage. The immune system of the person receiving the graft identifies it as damaged and, when attacking it, weakens the tissue. So what manufacturers currently do is to combine the cell cultures with a polyester-based synthetic matrix, which the white cells are unable to break down. However, their response is to induce chronic inflammation, which thickens and eventually blocks the inside wall of the prosthesis. The prosthesis must then also be replaced.
You have been working on the development of such artificial biological vessels for the past 20 years. What obstacles have you encountered?
I began working on the subject right from my PhD, which I obtained in 1996. To begin with, it was about being able to cultivate the patient’s own cells by inciting them to produce the collagen which strengthens their cohesion. Like that we were able to obtain very robust sheets of tissue, containing no synthetic compounds. We rolled these sheets around a rod to obtain several superimposed layers and placed the tissue in a bioreactor in order for the layers to meld. The walls of the resulting vessels were thick and resistant, able to withstand high pressures of up to 2,500 mm of mercury, i.e. a little less than an artery can tolerate without bursting (3,000 mmHg) but much more than normal blood pressure (80 to 120 mmHg). The first trials conducted in the years 2000 were very promising. But it was a very costly solution and would have been difficult to market. The production times were long and because it involved grafts produced from the patient's own cells (autologous grafts), it was impossible to have vessels available in advance when needed by the patient. So, when I joined Inserm Bordeaux in 2015, I developed a new approach: once the sheets of tissue are ready, the cells are killed without altering the collagen matrix. Like that, the universal and stabilized material could be stored and used on demand, even between unrelated individuals. Once implanted, we hope that the patient’s own cells will naturally recolonize it. Another thing we have changed is that rather than superimposing the sheets and waiting for them to meld, we now cut them into thin strands. We then twist them like threads and then weave or knit them to obtain vessels that are highly resistant.
How will you use this 2.5-million-euro five-year ERC funding?
We will be able to expand the team of the BioTis laboratory, the Inserm/Université de Bordeaux joint research unit specialized in tissue bioengineering which I head up. We will hire researchers, technicians and post-docs whose sole focus will be to develop the initial trials verifying the mechanical resistance of our artificial vessels and their good tolerance by the immune system. To begin with, this work will be conducted in sheep because their vessels are the same size as ours.