2024-07-10 18:05:28
MRI image showing the reconstructed pulmonary valve (red circles) that closes perfectly after 7 days of implantation. © Fabien Kawecki/Inserm
Inserm researchers have developed a pulmonary valve from human collagen. A device that could ultimately be a game-changer in the treatment of pediatric heart disease, such as tetralogy of Fallot. These results are part of the wider work carried out within the tissue bioengineering laboratory BioTis (Inserm/Bordeaux University) in Bordeaux, which works to develop tissues made from biological material obtained from human cells. The study, published in the journal Translational Medicine Scienceit opens up new therapeutic avenues in the long term for young patients suffering from tetralogy of Fallot, for whom current therapeutic options still cause numerous complications.
Tetralogy of Fallot is a congenital heart malformation that affects one in 4,000 births. It is characterized in particular by “pulmonary stenosis”, that is to say that the exit route of the blood from the right ventricle of the heart towards the pulmonary artery. diluted. This prevents the normal flow of blood to the lungs, reducing the patients oxygen level.
This anomaly can be corrected by surgery, the purpose of which is to restore normal blood flow through the pulmonary pathway by widening it. This involves removing the pulmonary valve, which must then be reconstructed, using synthetic TeflonTM membranes or using so-called “biological” sheets made from chemically treated animal tissue.
Both solutions have major disadvantages, firstly a reaction of the immune system, which seeks to reject these foreign bodies. Along with a chronic inflammatory reaction, this phenomenon can also lead to other complications such as thrombosis and calcification.[1]. In addition, there are valves made of these materials that help the development of bacterial infections. Finally, they are not designed to support the patient’s growth and change in morphology over time: this means that as the patient ages, further operations will be required to replace the anterior valve.
Valve from human cells
Therefore the team led by Inserm researcher Fabien Kawecki was trying to find new solutions. So she developed a “new generation” biological pulmonary valve, designed from collagen-rich sheets produced by cells. Collagen is a very abundant structural protein in the human body, which helps support many tissues and organs. The researchers therefore relied on the approach developed over the past ten years in the BioTis laboratory (Inserm/Bordeaux University), which consists of cultivating human cells in the laboratory to obtain extracellular matrix deposits.
These collagen deposits form sheets that can be used to design pulmonary valves, as in this study. A big advantage: because collagen does not vary from person to person, the body does not consider these sheets to be foreign bodies that are completely biological and non-chemically denatured.
In the study, Fabien Kawecki and his team tested the use of their biological leaflets to recreate a pulmonary valve in an “organic-synthetic” heart model developed by their American collaborators from Massachusetts Institute of Technology (MIT). It is a bio-artificial heart that reproduces the functioning of the human heart and controls the heartbeat using pneumatic muscles. From this model, valuable data can be gathered on the functionality of the valve. Then, working with cardiac surgeons from Bordeaux University Hospital, the scientists implanted the valve for seven days in an animal model (sheep), performing the same surgical procedures and using the same tools as those used to during this type of operation in humans.
“Thanks to our two models, we obtained a proof of concept that the valve we designed is functional and can be easily implanted following the same surgical procedures as in humans, which is promising if we want to move on to clinical studies within a few years. . The implantation of our valve made it possible to restore the direction of blood circulation through the pulmonary pathway without generating a valve leak. We also observed that after only 7 days after implantation, there was good integration of the valve with the animal’s native tissue. In addition, we saw on our valve the presence of smooth muscle cells that will play an important role in its remodeling and growth,” explains Fabien Kawecki.
From the data collected in the two models, the scientists were also able to develop a digital model that will allow testing the functionality and clinical utility of different biomaterials before implantation in animals.
« This digital model as well as the organo-synthetic heart could be valuable tools for researchers and surgeons, especially to allow them in the future to test new biomaterials and medical devices, as well as train approaches new surgery on animals and then on humans”, explains Fabien Kawecki.
For the team, the next step is to implant the valve over longer periods of time (16 weeks, then a year) in animal models, to ensure that it is functional in the long term and supports the animal’s growth with passage of time. . Even in the long term, if the results are inconclusive, clinical trials could be considered.
The team has already filed a patent for the use of the biomaterial designed in the laboratory as a pulmonary valve and in the future they hope to test its uses in various cardiovascular diseases in adults and children.
[1] Deposition of calcium salts in organic tissues
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