Biodegradable stents
Scientists develop stents from biopolymers
A team of Krasnoyarsk researchers from the Siberian Federal University, the Krasnoyarsk Scientific Center SB RAS and the Krasnoyarsk Center for Cardiovascular Surgery is working to create "ideal" stents from biopolymers. Scientists have managed to select such a composition of the material, in contact with which blood cells do not have negative effects. Biodegradable and biocompatible products should significantly facilitate the treatment of atherosclerosis. The large-scale research is supported by the Russian Scientific Foundation.
Article by Shishatskaya et al. The effect of the chemical composition and structure of polymer films made from resorbable polyhydroxyalkanoates on blood cell response is published in the International Journal of Biological Macromolecules.
Krasnoyarsk scientists are conducting long-term studies of natural polymers with a unique set of properties. These structural materials have biocompatibility and biodegradability, which opens up almost limitless prospects for practical applications, including in regenerative medicine. Products made of these materials are able to retain the shape that researchers give them, that is, they can be used to make various complex implants and volumetric products for tissue engineering.
Biodegradable polymers are produced by microbiological biosynthesis, a process in which specific bacteria accumulate a substance inside their cells. For the biosynthesis of polymers, bacteria have a special enzyme that connects individual organic molecules into long chains. These reserve macromolecules are synthesized by bacteria when they grow under suboptimal conditions, for example, when they lack nutrients.
As part of a project supported by the Russian Science Foundation, Krasnoyarsk scientists have started developing individual coatings for vascular stents. They are used after myocardial infarctions and to relieve patients from angina pectoris. The task arose in response to a number of medical problems with traditional vascular stenting. When installing a stent, which is made by filigree laser cutting of the thinnest, up to two millimeters in diameter, steel tubes, there is a risk of repeated narrowing of the vessel in the same place due to the fact that a foreign body irritates the vessel.
In fact, the need for a stent in the heart is short-lived, about two to three weeks. During stenting, an atherosclerotic lipid plaque is destroyed – an outgrowth that narrowed the vessel and caused discomfort and pain. The stent acts as a spacer, which prevents the compression that has become habitual and ensures stable blood flow. The reaction is eliminated in two to three weeks, after which the spacer is no longer needed.
However, it is impossible to remove the "ingrown" stent – it has become part of the vessel and interferes with the formation of a "healthy" inner layer of cells. A metallic foreign body becomes the cause of chronic inflammation and the development of repeated, often rapid, atherosclerotic changes. The vessel in this place becomes less durable than a healthy one, the wall is more fragile, which may be the cause of rupture, that is, vascular catastrophe.
It is not surprising that the world is developing temporary stents made of destructible materials – polymers or metals. Magnesium and alloys based on it are used as a biodegradable metal. The biocompatibility of such materials is low. In contrast, biopolymers of Krasnoyarsk scientists are not rejected by living tissues. Moreover, by changing the structure of the polymer during its biosynthesis, researchers can regulate the lifetime of the product in the body, its flexibility and elasticity, and the relief of the surface.
When developing bioengineered structures implanted into living tissue, it should be taken into account that their surface affects the activity of tissue cells. This is due to the transfer of mechanical force applied to the cell surface into biochemical reactions inside the cell. A cell in a tissue or organ is in a state of compression-stretching balanced from different sides. On the one hand, it is stretched from the outside by neighboring cells and external components of tissues – elements of the extracellular matrix. On the other hand, the forces formed by the interaction of the internal structures of the cell with the membrane act on it from the inside.
In response to changes in external physical parameters, the cell can change its shape, functional state, and even specialization. This means that by developing an external cellular framework with certain parameters, scientists can make it change in the right direction. For example, in the case of atherosclerosis, "prohibit" atherosclerotic plaques from re-forming, "ordering" the inner layer of vascular wall cells to form a strong cellular layer.
Currently, Krasnoyarsk scientists are studying the mechanical and chemical interactions between biopolymers of different compositions and blood cells of patients who have atherosclerotic plaques in the heart vessels. Blood for research is provided by the Krasnoyarsk Cardiology Center, where it is taken from patients who are planning to install stents. In laboratory conditions, cells from the blood of patients begin to accumulate lipids due to the fact that their donors suffer from atherosclerosis, that is, their lipid metabolism is "spoiled". The task of scientists is to study the nature of the interaction of cells with various materials, and, in the future, with the help of a biodegradable coating, to achieve the "shutdown" of negative reactions.
In addition to the visible accumulation of lipids – small dense droplets filling the cytoplasm, atherosclerotic cells after contact with the biopolymer significantly change the shape and production of molecules characteristic of the disease, such as prostaglandins and leukotrienes. Scientists have found that the reaction of cells to polymer films of different composition is different. In the future, this opens up opportunities for managing their condition.
"Our task is to bring the study to such a stage when it will be possible to recommend the composition of the material for coating a biodegradable stent for a person suffering from atherosclerosis of a specific stage and having certain shifts in homeostasis. The "ideal" material will allow the affected heart vessels to heal without a trace of the fact that they once had plaques. Subsequently, this material can be used for the production of the entire stent, and even for more complex implants, for example, fragments of vessels, valves and a whole heart," explains Ekaterina Igorevna Shishatskaya, head of the Department of Medical Biology at Siberian Federal University, chief researcher at the Institute of Biophysics of the FITC KNC SB RAS, Doctor of Biological Sciences.
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