A valve made of human collagen derived from cell cultures opens up new possibilities for treating pediatric heart diseases, according to a study published in Science Translational Medicine.
Two Types of Reconstruction
Researchers from the BioTis laboratory (Inserm/University of Bordeaux, Bordeaux, France) have developed a pulmonary valve using human collagen. Such a device could revolutionize the treatment of pediatric heart diseases like tetralogy of Fallot, a congenital heart malformation characterized by pulmonary stenosis. In this disease, the blood flow from the right ventricle of the heart to the pulmonary artery is restricted, preventing normal blood flow to the lungs and leading to a decrease in oxygen levels in the patient's blood.
This anomaly can be corrected through surgery, which aims to restore the normal blood flow to the pulmonary artery by widening it. This involves removing the pulmonary valve, which then needs to be reconstructed either using synthetic materials like Teflon membranes or through so-called "biological" leaflets made from chemically treated animal tissue.
Both solutions have major drawbacks, however. First, an immune system rejection reaction can occur, which, along with chronic inflammatory reactions, may lead to other complications such as thrombosis and calcification. Second, valves made from these materials are prone to bacterial infections. Nor are they designed to accommodate the patient's growth and morphologic changes over time. This means that as the patient ages, further operations will be necessary to replace the initial valve.
Creating a Valve
The team led by Inserm researcher Fabien Kawecki has developed a "next-generation" biologic pulmonary valve made from collagen-rich leaflets derived from cell cultures. The researchers relied on the approach developed over the past decade at the BioTis laboratory, which involves cultivating human cells in the laboratory to obtain collagen-rich extracellular matrix deposits.
These collagen deposits form leaflets that can be used to design, as in this study, pulmonary valves. A significant advantage is that these fully biological and nonchemically denatured leaflets are not subject to rejection by the body.
The researchers tested the use of their biological leaflets to reconstruct a pulmonary valve in an "organosynthetic" heart model developed by their American collaborators at the Massachusetts Institute of Technology in Cambridge. Then, working with cardiac surgeons from the Bordeaux University Hospital, Bordeaux, France, the scientists also implanted the valve for 7 days in an animal model (ie, a sheep), performing the same surgical procedures and using the same tools as those used in such operations in humans.
"Thanks to our two models, we have obtained a proof of concept that the valve we designed is functional and can be implanted easily following the same surgical procedures as in humans, which is promising if we want to advance to clinical studies within a few years. The implantation of our valve restored the blood flow direction through the pulmonary artery without causing valve leakage. We also observed that after only 7 days of implantation, there was good integration of the valve with the native tissue of the animal. Furthermore, we observed the presence of smooth muscle cells on our valve that will play a key role in its remodeling and growth," said Kawecki in an Inserm press release.
The team's next step is to implant the valve for longer periods (16 weeks, then 1 year) in animal models to ensure that it functions well in the long term and accommodates the animal's growth over time. In the longer term, if the results are positive, 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 hopes to test its utility in various cardiovascular diseases in adults and children in the future.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.