Inside the Agilent measurement suite at Imperial’s Molecular Sciences Research Centre. Credit: Imperial College London
Replacement heart valves that develop inside the body are one step closer to reality following studies by Imperial researchers. The results are published in Communication biology.
Surgery to replace faulty heart valves has been possible for more than 60 years, but the treatment has medical drawbacks, whether for mechanical or biological valves. What if the body’s natural repair mechanisms could be harnessed to build a living heart valve right where it’s needed? Recent studies by researchers at Harefield Hospital and Imperial’s National Heart and Lung Institute suggest this approach is entirely possible.
Heart valve replacement is a life-saving treatment, but it is rarely a long-term solution. Both mechanical and biological valves have their own drawbacks. Patients with mechanical valves must take medications for the rest of their lives to prevent blood clotting.
Biological valves, on the other hand, only last 10 to 15 years. Treatment is especially difficult for children with congenital heart defects because the valves do not grow with their bodies and must be replaced several times before they reach adulthood.
The new approach developed by Sir Magdi Yacoub’s team at Harefield and Imperial is much more adaptable. “The goal of the concept we developed is to produce a living valve in the body, which would be able to grow with the patient,” explains Dr. Yuan-Tsan Tseng, a biomaterials researcher working at the National Heart and Stroke Institute. lung. and the Harefield Cardiac Science Centre.
The procedure begins with a nanofibrous polymer valve, but made from a biodegradable polymer scaffold rather than a durable plastic. “Once inside the body, the scaffold recruits cells and controls their development, so the body functions as a bioreactor to grow new tissues,” explains Dr. Tseng. “The scaffolding gradually breaks down and is replaced by our body’s own tissues.”
The key innovation is the scaffolding material used to make the valve. “It has the ability to attract, harbor and instruct the appropriate cells in the patient’s body, thereby facilitating tissue generation and maintenance of valve function.”
Build, destroy
The design and manufacturing of the valve are detailed in an academic article, along with validation of its laboratory performance and initial results from animal testing. The valves were transplanted into sheep and monitored for up to six months.
“The valves worked very well,” says Dr. Tseng. “They continued to work throughout the six months of the trial and also showed good cell regeneration.”
In particular, the study shows that the scaffold was able to attract cells from the bloodstream that then developed into functional tissues, a process known as endothelial-to-mesenchymal transformation (EndMT). “We also saw nerves and fatty tissue growing into the scaffold, as would be expected in a normal valve.”
During this time, the polymer could degrade to make way for the new tissue. This degradation process was monitored using gel permeability chromatography (GPC) in the Agilent Measurement Suite (AMS), a facility at Imperial’s Molecular Sciences Research Center in White City, equipped with advanced analytical instruments provided by Agilent.
“GPC was able to tell us the molecular weight of the polymer in samples taken from the valves at different times during the in vivo study,” says Dr. Tseng. This showed that the structure was gradually degrading, but without affecting the performance of the valve.
“If there was no regeneration, the valve would collapse as the polymer degrades. But what we see is continuous functionality, meaning cell regeneration occurs over time. time. This proves that our idea of in vivo regeneration works.”
Further work is needed to determine exactly which processes cause polymer degeneration and how closely it is linked to tissue regeneration. “But tissue regeneration is certainly sufficient to ensure the structural integrity and functionality of the valve,” says Dr. Tseng.
Let’s move on to clinical trials
The next step is to continue animal studies, to follow the tissue regeneration process for longer. This data will be essential to obtain regulatory approval of the first clinical trials, hopefully within the next five years.
Additional work will also be needed on the processes used to manufacture the valves. “There are various improvements to be made on the manufacturing side, and we will potentially use the Agilent measurement suite again to help us optimize the polymer, so that it performs in the desired way,” says Dr. Tseng.
As work on the replacement valves progresses, the team will also begin seeking commercial partners to help with the final stages of clinical trials. “It requires a different type of expertise, which we don’t have in academia.”
Although the current focus is on heart valve replacement, this approach could have many other applications. “Once you have the scaffold, it becomes a technology platform that you can use to engineer other tissues,” says Dr. Tseng.
Possibilities include treating vascular conditions, such as repairing blood vessels damaged during dialysis and creating cardiac patches to repair damage to the heart.
More information:
Magdi H. Yacoub et al, Valvulogenesis of a living innervated lung root induced by an acellular scaffold, Communication biology (2023). DOI: 10.1038/s42003-023-05383-z
Provided by Imperial College London
Quote: New heart treatment could help the body develop a replacement valve (January 31, 2024) retrieved January 31, 2024 from
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