1. History of discovery
2. Physico-chemical properties of HA
3.Biological role of HA
4.Synthesis and metabolism of HA in the human body
5. Preparation and modification of HA
6. Active biological functions of HA in the human body
7.Use of HA in cosmetology and plastic surgery
8. Injection techniques for administering hyaluronic acid and their complications
1. History of discovery
Hyaluronic acid(hyaluronate, hyaluronan) (HA) is a non-sulfonated glycosaminoglycan that is part of connective, epithelial and nervous tissues. It is one of the main components of the extracellular matrix and is found in many biological fluids (vitreous body, synovial fluid, etc.). The name “hyaluronic acid” was given to this substance in 1934 by K. Meyer. The chemical structure of hyaluronic acid (was established in the 1950s by K. Meyer and J. Palmer, who first identified it from the vitreous humor of the eye.
2. Physico-chemical properties of HA
Hyaluronic acid is a polymer consisting of D-glucuronic acid and D-N-acetylglucosamine residues linked alternately by β-1,4- and β-1,3-glycosidic bonds. A HA molecule can contain up to 25,00 such disaccharide units. Natural HA has a molecular weight from 5 to 20,000 kDa, is also produced by some bacteria (e.g. Streptococcus) [Murry R. et al., 2009], but does not exist in a free state, only in the form of salts of Na, Ca, etc., therefore, when talking about HA, we always mean some kind of salt.
3.Biological role of HA
Even a 1% solution of HA has a noticeable viscosity, since its molecules form something like a network in water. It is not for nothing that hyaluronic acid is sometimes called a molecular sponge [Signore Jean-Marc, 1998]. Due to its physicochemical properties (high viscosity, specific ability to bind water and proteins and form proteoglycan aggregates), HA contributes to the manifestation of numerous functions of connective tissue and is one of the main components of the extracellular matrix, the vitreous body of the eye and synovial fluid. [Stroitelev V., Fedorishchev I., 2000].
Studies of HA have shown that the uniqueness of this substance also lies in the fact that HA molecules with different polysaccharide chain lengths have different effects on cellular behavior:
— Short chain HA(with a molecular weight of less than 30,000) have an anti-inflammatory effect;
— Medium molecular HA(with a molecular weight of more than 500,000) suppresses angiogenesis, inhibits cell migration and proliferation, as well as the production of interleukin-1b and prostaglandin E2, as a result of which it is widely used in ophthalmology and the treatment of post-traumatic and degenerative arthritis;
— High molecular weight fraction of HA with a pier weighing 50,000-100,000 has the ability to stimulate cell migration and proliferation in the skin, and also has a high water-holding capacity. One molecule of the high molecular weight fraction of HA binds up to 500 water molecules. Therefore, the dermis, which contains a significant amount of HA, is optimally saturated with water, which provides the skin with elasticity and resistance to external influences.
4.Synthesis and metabolism of HA in the human body
Unlike other glycosaminoglycans synthesized in the Golgi apparatus, GA is synthesized on the inner surface of the plasma membrane. As the polymer chain lengthens, HA is released through the membrane to its outer surface. Outside the cell, HA can form complexes with hyaluronate-binding proteins called hyalatherins.
All hyaladherins contain a hyaluronate binding motif or proteoglycan tandem repeat (PTR) in one (CD44 and TSG-6) or two (vernican, binding protein, aggrecan, neurocan, brevican) copies. Different tissues contain different sets of hyaladherins, which is due to the structural features and functions of specific connective tissue. Thus, aggrecan and a binding protein were found in cartilage, while versican was found in the softer connective tissue of the dermis.
The synthesis of hyaluronate is carried out by the enzyme hyaluronate synthase. In humans there are three hyaluronate synthases HAS1, HAS2 and HAS3. They are encoded by different genes, which are located on different chromosomes and descended from a common ancestor. Each of the synthesized HAS proteins (hyaluronate synthases) can play a specific role in the biosynthesis of hyaluronate:
— HAS1 protein carries out slow synthesis of high molecular weight hyaluronate;
— HAS2 protein significantly more active than HAS1 and also synthesizes high molecular weight hyaluronate (up to 2 x 106 Da);
— HAS3 protein the most active of the three HAS proteins, but synthesizes shorter hyaluronate chains ((2-3) x 105 Da).
Hyaluronate molecules of different lengths have different effects on cell behavior. This may play an important role in physiological regulation mechanisms.
HA is degraded by a group of tissue enzymes called hyaluronidases. The decomposition products of HA (oligosaccharides and extremely low molecular weight hyaluronates) exhibit proangiogenic properties (stimulate the formation of new capillaries from existing vessels. In addition, recent studies have shown that fragments of HA, unlike the native high molecular weight polysaccharide, are capable of inducing an inflammatory response in macrophages and dendritic cells for tissue damage and rejection of transplanted skin. The body of a 70 kg person on average contains about 15 grams of HA, a third of which is converted (broken down or synthesized) every day.
5. Preparation and modification of HA
For practical purposes in medicine and cosmetology, HA is isolated from various biological tissues - the vitreous body of animals, synovial fluid, umbilical cords, membranes of various strains of microorganisms, etc. The main and most promising source of HA is the combs of birds.
An equally important task is to purify HA extracts from foreign protein fractions and nucleic acids and then impart the desired properties to the drug by modifying it to ensure its rheological and viscoelastic properties, as well as increasing resistance to degradation under the influence of body enzymes and external factors. Such a change in the properties of HA expands the scope of application as a component of various drugs and medicinal substances.
One modification method is provided photopolymerization or photo-cross-linking of hyaluronic acid molecules under the influence of quantum/laser radiation of certain wavelengths from 514 to 790 nm.
6. Biological functions of HA in the human body
Regenerating: Strengthening the migration and secreting ability of fibroblasts
Anti-inflammatory: Improving blood microcirculation
Antimicrobial: Activation of bactericidal factors on the surface of the skin and wound surfaces
Antitoxic: Reduced endogenous intoxication rates
Immunomodulatory: Increased phagocytosis, changes in lymphocyte activity
Antioxidant: Acceptance of reactive oxygen species, blocking free radical oxidation of lipids
Hemostatic: Activation of hemostasis components with thrombus formation
Due to its unique properties, HA, as monotherapy or in combined synergy with quantum phoresis and other physiotherapeutic factors (electrophoresis, iontophoresis, magnetic therapy, etc.), is widely used in treatment and rehabilitation programs in various areas of medical practice and cosmetology: orthopedics, traumatology, sports medicine, surgery, gynecology, neurology, urology, dermatology, aesthetic medicine, etc.
7. Application of HA in cosmetology and plastic surgery
The presence of hyaluronic acid in the skin was first shown by K. Meyer in 1948. It has now been established that the skin (both epidermis and dermis) is one of the tissues with the highest content of hyaluronate, which largely determines not only the structure, but also the protective and regenerative properties of the skin.
Hyaluronic acid is a natural moisturizer and skin scaffold.
In the dermis, HA forms a framework to which other glycosaminoglycans (and primarily chondroitin sulfate) and proteins, called hyalathherins for their ability to selectively bind to HA, are attached to form a polymer network that fills most of the extracellular space, providing mechanical support for tissues and rapid diffusion of water-soluble substances. molecules and cell migration. On the other hand, in the epidermis, HA is localized in the pericellular space, creating a cell membrane that protects it from the action of toxic substances.
It should be noted that only the HA fraction with a molecular weight of 50,000-100,000 has the ability to stimulate cell migration and proliferation in the skin, and also has the highest possible level of water-holding capacity. One molecule of the high molecular weight fraction of HA binds up to 500 water molecules. Therefore, the skin, containing a significant amount of HA, is maximally saturated with water, which provides the skin with elasticity and resistance to external influences.
One of the main signs of skin aging is a decrease in HA content and a closely related decrease in the supply of moisture in the skin. The largest amount of hyaluronic acid is found in the connective tissue of newborns. Up to 30-35 years, the amount of HA in the dermis remains quite stable, after which it begins to decrease quite quickly, which is signaled by the signs of biological aging that appear at this time - loss of moisture, deterioration of skin elasticity and tone, and the appearance of wrinkles.
In addition, with age, the own synthesis of hyaluronic acid in the dermis and epidermis decreases and its destruction accelerates under the influence of various external and internal factors [Signore Jean-Marc, 1998].
Due to its unique properties, HA is widely used in various areas of medical practice and cosmetology.
Currently extremely popular are procedures aimed at rejuvenating the skin of the face, hands and other exposed parts of the body and eliminating visible signs of aging through intradermal injection of HA, which is called hyaluronic biorevitalization (hyaluroplasty), that is, restoring the amount of HA in the skin characteristic of young age.
8. Injection techniques for administering hyaluronic acid and their complications.
The traditional form of such replenishment is the method of injecting hyaluronic acid into the skin, which has a number of disadvantages and complications that depend on many external and internal factors, including those associated with personnel errors, individual characteristics and increased sensitivity of the skin to the allergenic nature of the drug entering the blood, as well as the presence of concomitant diseases and contraindications.
The most common complications of injection administration of HA include:
- emerging swelling, severe granulomatous reactions, varying degrees of edema and erythema at the injection sites due to local hypersensitivity reactions such as angioedema, which can persist for a long time and have negative aesthetic consequences;
— after injection of HA, a recurrence of herpetic eruptions quite often occurs as a result of stimulation of the latent herpes virus, especially in the lip area;
- the use of an infected or poorly purified drug provokes the development of infectious skin processes or reactions to foreign bodies;
- changes in skin pigmentation in the injection area;
- inflammatory skin diseases in the areas to be treated make injection biorevitalization impossible - the consequences can be very negative and provoke diffusion of the inflammatory process;
— the presence of a number of concomitant diseases;
— injection biorevitalization during pregnancy and breastfeeding is also unacceptable;
— complications after injection biorevitalization are inevitable if there is an allergy to the components of the drug or autoimmune diseases;
- taking anticoagulants (blood thinning drugs, for example acetylsalicylic acid in aspirin) can also cause negative consequences of injection biorevitalization;
— if there is an increased tendency to form keloid scars, injection biorevitalization is not recommended, since the consequences can be unpredictable;
— by manipulating the needle, the cosmetologist is not able to fully control the subcutaneous area of drug administration and avoid introducing the drug into a blood vessel, especially in the eye area. On the other hand, too superficial administration of the drug can cause the appearance of uneven skin surfaces, while at the same time, excessively deep administration may be ineffective;
- pain of the procedure;
- economic factor and relative high cost of the procedure.
All these negative manifestations of the hyaluronic acid injection technique can be avoided by using the alternative technology of laser phoresis (quantophoresis) QUANTOL.
This technique is not inferior in its effectiveness in cosmetology and even surpasses the still existing and most common method of injecting hyaluronic acid into the skin, which has a number of disadvantages and complications, depending on many factors, including those related to personnel errors, local skin factors, hypersensitivity of the skin, the presence of chronic diseases.
With this method of biorevitalization, a much more voluminous and uniform distribution of hyaluronic acid in the skin is achieved compared to injection methods.
In essence, QUANTOLA technology is a combined technique of photodynamic rejuvenation (biorevitalization) of the skin and attracts the attention of specialists due to its safety, effectiveness, painlessness, absence of unwanted side effects and availability for widespread use.
In a broader aspect, in addition to the purposes of skin rejuvenation, this method can be successfully used to treat a number of skin diseases, such as photodamage to the skin, hyperplasia of the sebaceous glands, acne and many other conditions encountered by dermatologists and cosmetologists, etc. (learn more...)
The site provides reference information for informational purposes only. Diagnosis and treatment of diseases must be carried out under the supervision of a specialist. All drugs have contraindications. Consultation with a specialist is required!
Hyaluronic acid is a polymer molecule consisting of small compounds with a carbohydrate structure. This compound was discovered about 75 years ago, and is still being intensively studied by chemists, biologists, pharmacists, doctors and scientists in other biomedical specialties. The physical properties of hyaluronic acid are unique - it is capable of holding water molecules, forming a gel-like structure, and in addition, this compound is involved in many important processes in the human and animal body, such as cell division and migration, gene switching, wound healing, fertilization, growth and development of the fetus, the formation of malignant tumors, etc.Currently, hyaluronic acid is widely used in aesthetic medicine (it is part of cosmetic products such as creams, masks and others, and is also used for biorevitalization procedures and other manipulations aimed at slowing down the aging process and maintaining youthful tissues). In addition to the aesthetic field, hyaluronic acid is widely used in medical practice, for example, in the treatment of eye and joint diseases, in the complex therapy of malignant tumors, in wound healing and in immunology. Let's consider the properties and use of hyaluronic acid in various fields (both aesthetic and medical).
Hyaluronic acid - general characteristics, properties and methods of production
Hyaluronic acid is a polysaccharide, which means that its molecule consists of many identical small fragments, which in their structure are carbohydrates (simple saccharides). Simple sugars join together in a chain and form a long molecule of hyaluronic acid. Depending on the number of fragments that make up the hyaluronic acid molecule, it can have different weights and lengths. Based on the mass of the molecule, two types of hyaluronic acid are distinguished - high molecular weight And low molecular weight. High molecular weight varieties of hyaluronic acid are molecules with a mass of more than 300 kDa. All hyaluronic acid molecules with a mass of less than 300 kDa are classified as low molecular weight. Both types of the substance have a number of identical properties, but at the same time, some other physical properties and the biological role of high molecular weight and low molecular weight hyaluronic acids are different.
Thus, both high and low molecular weight hyaluronic acid are able to bind and retain water molecules, forming a jelly-like mass. This jelly-like mass has a certain viscosity, allowing it to serve as an ideal substrate for any fluids and lubricants in the body (for example, saliva, vaginal and joint lubrication, amniotic fluid, etc.), as well as for the extracellular matrix in which biochemical reactions occur and undergo other important processes. The degree of viscosity of the jelly-like mass formed by hyaluronic acid depends on its mass. The greater the molecular weight of the hyaluronic acid molecule, the more viscous will be the jelly-like mass formed by it in combination with water.
The extracellular matrix, formed by a jelly-like mass of water retained by hyaluronic acid, is a unique environment that connects the cells of organs and systems with each other, and also ensures their interaction. Cells and biologically active substances move through the intercellular matrix, entering it from blood vessels. It is thanks to the jelly-like viscous matrix that various substances can reach every cell of an organ or tissue, even if there is no blood vessel passing next to it. That is, some substance or cell exits a blood vessel into the intercellular matrix and passes through it to cellular structures lying deep in the tissues and not in contact with the blood vessels.
In addition, cell waste products, toxins of viruses and bacteria, as well as dead cellular structures are removed from organs and tissues precisely through the intercellular matrix. First, they enter the intercellular substance, then move along it towards the lymphatic or blood vessels, upon reaching which they penetrate into them and are finally eliminated from the body. Such movement between cells in the intercellular matrix is possible precisely due to its jelly-like consistency provided by hyaluronic acid.
In addition, hyaluronic acid is a necessary component of intra-articular lubrication and eye fluid, and is also part of the dermis and connective tissue. This compound imparts viscosity to intra-articular lubricant and eye fluid, ensuring their optimal properties. In the dermis, hyaluronic acid keeps collagen and elastin fibers in the correct position, thereby maintaining skin turgor, elasticity and youth. In addition, by binding water, hyaluronic acid provides the optimal amount of moisture in the skin, which also prevents aging and the appearance of wrinkles. In connective tissue, hyaluronic acid also ensures its turgor, elasticity, extensibility and sufficient moisture.
With a lack of hyaluronic acid, tissues dry out due to a lack of water, which is not retained in them. As a result, tissues become thinner, brittle, inelastic and easily broken, which leads to their aging and the development of various diseases. Hyaluronic acid also takes part in a number of very important processes, such as cell migration and reproduction, gene switching, conception and subsequent growth of the fetus, the formation of malignant tumors, the development of the immune response, etc. Thus, it is simply impossible to overestimate the properties of hyaluronic acid necessary for the normal functioning of organs and tissues at the cellular level.
The body of a person weighing 70 kg constantly contains about 15 grams of hyaluronic acid. Moreover, every day approximately 1/3 of the total amount of hyaluronic acid found in various organs and tissues is broken down and utilized, and new molecules are formed instead. The half-life of hyaluronic acid molecules in joint lubricants ranges from 1 to 30 weeks, in the epidermis and dermis - 1 - 2 days, and in the blood - several minutes. With age, the body loses the ability to synthesize hyaluronic acid in the required quantity, as a result of which the aging process begins. That is why, to slow down aging, mature people need to obtain hyaluronic acid from the outside, from food or from dietary supplements (dietary supplements).
For use in medicine and the aesthetic industry, hyaluronic acid is produced on an industrial scale from two types of raw materials:
1.
Vertebrate tissues;
2.
Bacteria that form a protective capsule of hyaluronic acid molecules (for example, hemolytic streptococci types A and B).
To obtain hyaluronic acid, the following tissues of vertebrate animals, which contain the largest amounts of this substance, are most often used:
- Rooster combs;
- Vitreous body of the eye;
- Synovial fluid of joints;
- Hyaline cartilage;
- Umbilical cord;
- Epidermis and dermis of the skin;
- Amniotic fluid.
Bacteria are used to produce hyaluronic acid in the following way: the required strain is placed on a nutrient medium and provides it with ideal conditions for reproduction. When the nutrient medium becomes viscous, this means that the bacteria have produced a sufficiently large amount of hyaluronic acid, which only needs to be isolated and cleaned of impurities.
Hyaluronic acid, isolated from animal raw materials and bacteria, has a significant drawback - it contains impurities of proteins and peptides, which cannot be completely removed even after special treatment. These proteins and peptides can provoke allergic reactions in people, which narrows the scope of application of hyaluronic acid.
Ready-made hyaluronic acid is produced by pharmaceutical factories in the form of powders and granules containing molecules of varying weights. These powders are used to prepare solutions, which are then added to creams, masks, medications, etc. Before use, prepared solutions of hyaluronic acid are sterilized in autoclaves.
Biological role of hyaluronic acid
Hyaluronic acid is a polysaccharide with a high degree of hydration (bound to water) and is part of the intercellular matrix, due to which it has very diverse functions and takes part in the processes of reproduction, migration, recognition and differentiation of cells of various organs and tissues.Depending on the number and size of hyaluronic acid molecules in the intercellular matrix, gels of varying degrees of viscosity are formed, which further determine the properties and functions of tissues, organs, and systems. Thus, gels formed by hyaluronic acid determine the amount of water in the tissue, the intensity of ion exchange in cells (potassium, sodium, magnesium, zinc, etc.), the rate of transport of various biologically active substances and toxins, the impermeability of the medium to large molecules and cells, and etc.
The ability of hyaluronic acid to make any part of the gel medium of the intercellular matrix impermeable to large molecules provides tissues with protection from toxins and the penetration of microbes (bacteria, protozoa and fungi).
Retention of a large amount of water by hyaluronic acid creates incompressibility and swelling effects, on the basis of which effective resistance to various mechanical effects aimed at compressing tissues and organs is realized. Thanks to this, organs and tissues retain their shape and are not subject to compression, and, consequently, injury. It is thanks to this effect of hyaluronic acid that we can, for example, squeeze the skin with our fingers without damaging its structures.
The viscosity of the joint fluid created by hyaluronic acid allows it to act as a lubricant for the rubbing cartilaginous surfaces of the two articulating bones, and also reduce the negative effects of excess pressure.
It is an aqueous solution of hyaluronic acid that fills the vitreous body of the eye, as well as an integral part of other structures of this organ. Hyaluronic acid is very important for the normal functioning of the eye, since its solutions are transparent and stable, which creates the necessary environment for the passage of a light beam to the retina without any distortion.
Hyaluronic acid plays a huge role in egg fertilization. The fact is that when leaving the ovary during ovulation, the egg is covered with two structures that protect it, called the zona pellucida and the corona radiata. Both the zona pellucida and the corona radiata in the intercellular matrix contain a large amount of hyaluronic acid, thanks to which they, in fact, exist. The egg is capable of fertilization only as long as its corona radiata and zona pellucida are completely intact. Once the corona radiata is destroyed in the fallopian tube, the egg will lose its ability to fertilize and die. Thus, if there is a lack of hyaluronic acid in the body, even healthy and full-fledged eggs can be useless, since they quickly die in the fallopian tube, being unable to be fertilized by sperm.
In addition, after fertilization, the remains of the zona pellucida with hyaluronic acid prevent the already fertilized egg from sticking to the walls of the fallopian tube, which is a mechanism for preventing ectopic pregnancy.
Hyaluronic acid also plays a huge role in subsequent fetal growth after fertilization. The fact is that whole molecules and fragments of hyaluronic acid trigger the process of division, migration and maturation of cells in the fertilized egg, as well as the formation of organs and systems from them.
Inside cells, hyaluronic acid takes part in the process of division, that is, it is necessary for the reproduction and formation of new cellular elements to replace old or damaged ones. Thanks to this effect, hyaluronic acid stimulates the process of repairing damage in organs and tissues. For example, in case of bone fractures, it is hyaluronic acid that stimulates the rapid fusion of fragments. Stimulation of repair processes occurs not only due to the activation of cell division, but also due to the ability of hyaluronic acid to activate the growth of blood vessels, which are necessary for newly forming tissue. Unfortunately, the ability of hyaluronic acid to stimulate the growth of blood vessels can also play a negative role, for example, during the growth of a malignant tumor. After all, the faster new vessels that feed the tumor are formed, the faster it increases in size, and the sooner it metastasizes.
Hyaluronic acid is also a component of innate immunity, which every person possesses from the moment of birth. In the skin and connective tissue, hyaluronic acid performs a number of very important functions due to the fact that it maintains collagen and elastin threads in their normal position and condition. Thus, this molecule protects the skin, preventing pathogenic microbes from penetrating deeper from its surface in the presence of damage (wounds, scratches, etc.). In addition, hyaluronic acid maintains the hydrobalance of the dermis and epidermis, reducing water evaporation and at the same time helping to attract and retain moisture from the air on the skin surface. Thanks to these properties, hyaluronic acid moisturizes the skin and also makes it smooth and elastic, preventing damage, thinning and drying, and thereby slowing down aging.
Summarizing the above, we can summarize that All types of hyaluronic acid have the following properties:
- Maintains and restores the normal degree of hydration (moisture) of the skin;
- Improves the elasticity of tissues, including skin;
- Normalizes tissue tone, including skin;
- Improves microcirculation;
- Accelerates the process of cell renewal in all tissues, including the skin;
- Relieves inflammation and eliminates swelling of the skin.
Low molecular weight varieties of hyaluronic acid, having a mass of less than 30 kDa, have the following properties:
- They pass through barriers formed by cell membranes, as a result of which they can penetrate from the surface of the skin into the deep layers of the dermis;
- Stimulate the growth of lymphatic and blood vessels;
- Improve microcirculation and skin nutrition.
- Accelerate wound healing;
- Stimulate cell division;
- Accelerate cell migration into the wound.
- Suppress cell division and migration to the area of damage;
- Do not penetrate from the surface of the skin into the deeper layers;
- Suppress the growth of lymphatic and blood vessels;
- Stop inflammation;
- Prevents cartilage destruction.
Areas of application of hyaluronic acid
Hyaluronic acid is widely used in the aesthetic field and in applied medicine in areas such as ophthalmology, arthrology, oncology, wound healing and immunology. Let's look at ways to use hyaluronic acid in various areas.Hyaluronic acid in the aesthetic field
Modern aesthetic medicine and cosmetology cannot be imagined without hyaluronic acid, since it is used very widely. Thus, in cosmetology, hyaluronic acid is included in various creams, serums, masks, gels and other products designed to moisturize, rejuvenate or reduce the severity of age-related changes in the skin.In aesthetic medicine, hyaluronic acid is the most popular product used to rejuvenate the skin, as well as eliminate age-related changes and “minus tissue” defects that have arisen after surgical interventions. Hyaluronic acid is used in injection rejuvenation techniques, such as filler implantation, biorevitalization and mesotherapy. The widespread use of this compound in injection methods of aesthetic medicine is due to a number of factors: firstly, the introduction of hyaluronic acid into the skin is safe, since allergic reactions to the drug do not occur; secondly, an implant made from a long hyaluronic acid molecule lasts for a long time, that is, the effect of the procedure lasts from 1 to 1.5 years. Finally, hyaluronic acid injections are easy to administer and painless.
Thus, it is obvious that hyaluronic acid is a very important component of modern cosmetics and a necessary substance for a number of non-surgical skin rejuvenation methods. Let's take a closer look at how hyaluronic acid is used in cosmetic products and used in non-surgical skin rejuvenation methods.
Injections with hyaluronic acid (hyaluronic acid injections)
The general name “hyaluronic acid injections” usually refers to several methods of non-surgical skin rejuvenation and elimination of the severity of age-related changes, which are united by the common essence of their production - the introduction of “hyaluronic acid” preparations into the structures of the skin using injections. That is, hyaluronic acid is injected into the skin using an ordinary syringe or a special roller. After injections of hyaluronic acid, made by any method, a person’s skin is smoothed, wrinkles either completely disappear or their severity becomes less pronounced, turgor appears and sagging is eliminated, and the degree of moisture in the structures of the skin increases. After all, skin aging, the appearance of wrinkles, sagging, dryness and dullness are caused precisely by a deficiency or decrease in the amount of hyaluronic acid in the deep layers of the skin, and therefore its management is an effective way to rejuvenate and eliminate dryness. Methods collectively called “hyaluronic acid injections” include the following procedures:
- Biorevitalization;
- Bioreparation;
- Contour plastic with fillers.
So, mesotherapy produced according to the principle “rarely, little, in the right place.” That is, hyaluronic acid is injected in small quantities only into those areas that need correction (for example, in the area of wrinkles, etc.). In addition, the "rare" principle means that injections are given once every few days. Mesotherapy has a cumulative effect due to the fact that hyaluronic acid is introduced in small quantities, and therefore, to obtain a good result, it is necessary to make several injections into the same area. The effect of mesotherapy lasts for several months.
Biorevitalization is performed using the same injection techniques (papular, tracer, canal) as mesotherapy, but large quantities of high molecular weight hyaluronic acid are used. Therefore, biorevitalization is performed at one time. This procedure gives immediate and delayed results. Immediate results include smoothing of wrinkles, which is noticeable immediately after the procedure. However, this immediate effect lasts approximately 1 – 2 weeks, after which it disappears. Next, the hyaluronic acid introduced into the skin is destroyed by special enzymes, and short fragmentary molecules are formed. These molecules stimulate the production of your own hyaluronic acid, collagen and elastin, which is the main goal of the biorevitalization procedure, since as a result of this process restoration and rejuvenation of the skin occurs. It is the restoration of the structures of aging skin that is the long-term result of biorevitalization, which is manifested by an improvement in tone, the disappearance of sagging, and a decrease in the number and depth of wrinkles. Long-term results of biorevitalization last for 1 – 1.5 years.
Bioreparation is a procedure similar to biorevitalization. However, bioreparation differs from biorevitalization in that its production uses complex preparations containing, in addition to hyaluronic acid, vitamins, minerals and other biologically active substances. As a result of the introduction of hyaluronic acid, vitamins and minerals into the skin structures, a long-lasting and pronounced rejuvenation effect is achieved, and minor unevenness and defects of the skin (for example, scars, acne marks, etc.) are eliminated.
Contour plastic with fillers is the introduction of special long threads of high molecular weight hyaluronic acid stitched together into certain areas of the skin that require correction. These threads are called fillers and are located on problem areas. Thanks to the introduction of fillers, you can correct the line of your cheekbones, the shape of your face, eliminate bags under the eyes, etc.
All hyaluronic acid injection methods are performed under local anesthesia, so the procedures themselves are painless. However, after the local anesthetic wears off, you may experience mild pain for 2 to 4 days, as well as persistent swelling and redness of the skin.
Lip augmentation with hyaluronic acid
This procedure is a private variant of hyaluronic acid injections, which are performed in the lip contour area. When hyaluronic acid in the form of fillers is injected into the lips, it fills the tissue and attracts water, which leads to an increase in their volume, and also makes the contour clearer and more beautiful. As a result, lips become fuller, plump and smooth with a clear contour, and also acquire a rich color. The achieved result lasts approximately 8 – 18 months. During the procedure, a small volume of hyaluronic acid is injected into the lips through puncture injections. Depending on the amount of hyaluronic acid injected, lip volume can be increased moderately or significantly. The more hyaluronic acid is introduced, the more the lip volume will increase.
The procedure itself lasts half an hour and is carried out under local anesthesia, and the full result is formed in two days. After lip augmentation with hyaluronic acid, swelling, redness and pain may persist for 2 to 7 days, which then completely disappear.
Hyaluronic acid under the eyes
Hyaluronic acid can be used to eliminate wrinkles and dark circles under the eyes, as well as make the thin skin in the area more elastic, firm and hydrated. Hyaluronic acid under the eyes can be used both in the form of injections and as part of special creams, serums, gels or mousses containing it as an active component.Indications and contraindications for hyaluronic acid injections (including for lip augmentation)
Hyaluronic acid injections using various methods are indicated in the following cases:- Dry and dehydrated skin;
- Loose skin on the face, abdomen, thighs and shoulders;
- Wrinkles in the eye area, oval face and décolleté;
- Circles under the eyes;
- Dull and unhealthy complexion;
- Enlarged pores on the skin of the face;
- Increased sebum production;
- Facelift;
- Improving the cheekbone line;
- Elimination of wrinkles;
- Increasing the amount of moisture in the skin;
- Increased skin elasticity and turgor;
- Normalization of skin texture;
- Increasing volume and improving lip contour.
- Intolerance or allergic reactions to hyaluronic acid;
- During pregnancy and breastfeeding ;
- Acute period of any acute and infectious diseases;
- Autoimmune diseases;
- Connective tissue pathology;
- Malignant tumors;
- Hypertonic disease;
- Tendency to form scars on the skin;
- Diabetic angiopathy;
- Blood clotting disorders;
- The presence of inflammation or moles in the area of the intended injections;
- Skin diseases;
- Taking medications that affect blood clotting (anticoagulants, antiplatelet agents, etc.).
Preparations for injections of hyaluronic acid
Currently, a variety of preparations are used for hyaluronic acid injections, produced in different countries and intended for different purposes. Below in the table we provide a list of the main high-quality certified hyaluronic acid preparations, indicating the indications for their use and the duration of the achieved effect.| Hyaluronic acid preparation | Indications for use of the drug | Duration of the achieved effect |
| Varioderm | Correction of medium and deep wrinkles Lip contour correction | 6 – 12 months |
| Varioderm Fineline | Elimination of superficial wrinkles Correction of crow's feet Correction of the red border of the lips | 6 – 12 months |
| Varioderm Plus | Correction of deep wrinkles Correction of facial oval | 6 – 12 months |
| Varioderm Subdermal | Correction of very deep wrinkles Increase in tissue volume | 6 – 12 months |
| Hylaform (Hylan-B age) | Lip shape correction | 12 months |
| Hyalite (Puragen) | Lip shape correction Elimination of nasolabial folds | 12 months |
| Teosyal Global Action | Correction of medium wrinkles | 12 months |
| Teosyal Deep Lines | Correction of deep wrinkles and skin folds | 12 months |
| Teosyal Kiss | Correction of lip volume and contour | 12 months |
| Prevelle | 3 – 6 months | |
| Captique | Correction of fine and medium wrinkles | 3 – 6 months |
| Repleri | Correction of medium and deep wrinkles | 12 – 18 months |
| Juvederm Ultra | 6 – 8 months | |
| Juvederm Ultra Plus | Correction of medium to deep wrinkles and folds | 6 – 12 months |
| Sirgiderm 18 | Correction of fine wrinkles | 6 months |
| Sirgiderm 30 | Elimination of deep skin depression Replenishment of tissue volume deficit | 9 months |
| Sirgiderm 24 XP | Elimination of moderate skin depression Lip contour correction | 9 months |
| Sirgiderm 30 XP | Elimination of deep and moderate skin depression Replenishment of tissue volume deficit Correction of lip contour and shape | 9 months |
| Belotero Basic | Scar removal Correction of deep and medium wrinkles or furrows Correction of facial contours Increase in volume and correction of lip contour | 6 – 9 months |
| Belotero Soft | Correction of fine superficial wrinkles | 6 – 9 months |
| Joliderm 24+ | Correction of deep expression wrinkles Correction and restoration of lip contour | 6 – 9 months |
| Jolidermis 24 | Correction of medium and deep expression wrinkles | 6 – 9 months |
| Joliderm 18 | Correction of fine wrinkles | 6 – 9 months |
| Restylane | Correction of moderate wrinkles | 6 – 12 months |
| Restylane Lipp | Increased lip volume Correction of the red border of the lips | 6 – 12 months |
| Restylane Perlane | Correction of deep folds Correction of facial oval | 6 – 12 months |
| Restylane SubQ | Elimination of age-related tissue volume deficit Elimination of soft tissue asymmetry | 12 – 18 months |
| Restylane Touch | Correction of very fine wrinkles (including in the orbital area of the eye and mouth) | 6 months |
| Eugulon B | Correction of fine and deep wrinkles and post-acne | 6 months |
| Hyaluform | Correction of fine wrinkles | 6 – 7 months |
| Hyaluform 1.8% | Correction of average wrinkles and folds | 8 – 9 months |
| Hyaluform 2.5% | Elimination of tissue volume deficit | 6 – 8 months |
| Gialripayer-0.1 | Correction of fine and deep wrinkles | 10 – 14 months |
Hyaluronic acid before and after – photo
This photograph shows the effect achieved by injections of hyaluronic acid produced using the biorevitalization method.
This photo shows the effect of hyaluronic acid injections with Restilane.
Lips after hyaluronic acid – photo
This photo shows the effect of increasing lip volume with hyaluronic acid.
Cream, serum and masks with hyaluronic acid
Various creams, masks, serums and other cosmetic products with hyaluronic acid are intended for external use to moisturize the skin, as well as reduce the severity of age-related changes. Cosmetics with hyaluronic acid tighten the skin, reduce sagging, rosacea and the size of enlarged pores, as well as even out the complexion and improve the texture of the skin. However, in order to get a visible effect from cosmetics with hyaluronic acid, they must be used regularly for at least a month.When choosing a cosmetic product, you need to focus on the quantity and quality of hyaluronic acid in it. Thus, serums contain the highest concentration of hyaluronic acid, so these cosmetics are recommended to be chosen for caring for skin that is in poor condition, as well as for obtaining the fastest possible effect. It is recommended to use serums with hyaluronic acid at the initial stage, and then switch to using creams with hyaluronic acid.
Creams may contain high or low molecular weight hyaluronic acid. High-molecular hyaluronic acid in the creams covers the skin with an invisible film, from which it is absorbed into the upper layers of the epidermis, making it moisturized, tightened, with an even and radiant color. Low molecular weight hyaluronic acid is able to be absorbed from the surface into the deep layers of the skin, where it stimulates the production of collagen and elastin, which leads to a more pronounced and lasting effect. However, creams containing low molecular weight hyaluronic acid are much more expensive than cosmetics containing a high molecular weight form of “hyaluronic acid”. Therefore, to correct superficial age-related changes, it is optimal to use creams with high molecular weight hyaluronic acid. Accordingly, to correct and reduce the severity of deep age-related changes, it is necessary to use creams with low molecular weight hyaluronic acid.
Masks with hyaluronic acid are used according to the same principles as creams. Creams and serums can be used daily, and masks – 1 – 2 times a week. All products with hyaluronic acid must be used only at above-zero temperatures, since in the cold its molecules crystallize and can damage the skin. Therefore, in winter, it is recommended to apply products with hyaluronic acid only in the evening, when you no longer plan to go outside.
However, it must be remembered that cosmetics with hyaluronic acid are not recommended for use by people under 25 years of age, as this may cause the opposite effect. The fact is that in young women, the skin itself produces a sufficient amount of hyaluronic acid and does not need intensive care, and therefore the constant supply of this substance from the outside can lead to the fact that the skin stops producing it. As a result, premature aging of the skin will occur.
Currently, creams, serums, masks and other cosmetics are produced by many companies, so purchasing them is not a problem. Some of the best cosmetics with hyaluronic acid are creams, masks, mousses and serums produced by European, Asian and American companies.
Hyaluronic acid preparations for facial skin: application (injection), effects, possible complications, recommendations of a dermatocosmetologist - video
Creams and injections with hyaluronic acid: how they work, in what cases they are used - video
Creams for moisturizing dry skin: with hyaluronic acid, with film-forming substances, with hydroxy acids - video
What is the difference between the effects of cream, serum and hyaluronic acid injections (answer from a cosmetologist) - video
Hyaluronic acid for joints
Healthy joints always contain a small amount of fluid, which acts as a lubricant. This liquid contains hyaluronic acid, which gives it the necessary properties. With various joint diseases, the concentration of hyaluronic acid in the joint fluid decreases by 2–4 times. Therefore, a method of treating joint diseases is currently being successfully used, which consists of introducing high-molecular hyaluronic acid into its cavity.When hyaluronic acid is injected into a joint for osteoarthritis, pain is relieved and its functional activity is improved, which allows a person to move normally and lead a normal lifestyle. In addition, the use of hyaluronic acid restores the properties of intra-articular fluid, suppresses the inflammatory process and stimulates the restoration of normal tissue structure.
Currently, the following hyaluronic acid preparations are used for joint diseases:
- Viscorneal forto;
- Viscosil;
- Sinvisk (Gilan G-F 20);
- Sinokrom;
- Suplazin;
- Ostenil.
Hyaluronic acid in ophthalmology
Hyaluronic acid preparations are widely used in local and systemic treatment of eye diseases. Thus, hyaluronic acid is included in the composition of “artificial tears” eye drops intended for the treatment of dry cornea. Hyaluronic acid is also used for eye surgery in order to create an optimal operating environment and protect tissue from accidental damage. Hyaluronic acid in wound healing
Hyaluronic acid suppresses the inflammatory process and activates the processes of restoration of normal tissue structure, due to which it is successfully used in the healing of wounds, burns and trophic ulcers. To heal wounds, hyaluronic acid is injected into a special dressing material, which is used to cover various damage to the skin, and the dressings are periodically changed.Bioexplants with hyaluronic acid (thin film) are used to cover sutures on the intestines after surgical interventions, which significantly accelerates wound healing and tissue restoration. In addition, bioexplants with hyaluronic acid are used during laparoscopic operations to cover intestinal loops to prevent accidental injury.
Hyaluronic acid - reviews
Most reviews of hyaluronic acid (from 85 to 90%) in cosmetics are positive, due to the visible aesthetic effect. Reviews indicate that salon procedures with hyaluronic acid very effectively moisturize the skin, make it smoother and more elastic, as a result of which fine wrinkles are smoothed out and new ones do not form. In addition, many reviews indicate that the use of creams with hyaluronic acid leads to the same effect as salon procedures, but only more slowly. If the effect of a salon procedure is noticeable immediately, then when using creams or masks it appears only after a month.Molecular formula: (C14H21NO11)n
Solubility in water: soluble (sodium salt)
LD50:
2400 mg/kg (mice, oral administration, sodium salt)
4000 mg/kg (mice, subcutaneous administration, sodium salt)
1500 mg/kg (mice, intraperitoneal administration, sodium salt)
Related compounds: D-glucuronic acid and DN-acetylglucosamine (monomers)
Hyaluronic acid (hyaluronate or HA) is an anionic, non-sulfated glycosaminoglycan, widely distributed in connective, epithelial and nervous tissue. It is unique among glycosaminoglycans in that it is a non-sulfated form, is formed in the plasma membrane rather than in the Golgi, and can reach very large sizes, with molecular weights often reaching millions. As one of the main components of the extracellular matrix, hyaluronic acid significantly promotes cell proliferation and migration, and may also be involved in the development of some malignant tumors. The average person weighing 70 kg (154 lb) has about 15 grams of hyaluronic acid in their body, one-third of which is replenished (degraded and synthesized) every day. Hyaluronic acid is also a constituent of the streptococcal group A extracellular capsule A, and is believed to play an important role in virulence (the degree to which a microorganism is pathogenic).
Medical use
Hyaluronic acid is sometimes used to treat osteoarthritis of the knee as an injection into the joint. The effectiveness of hyaluronic acid in this use, however, has not been proven, and such use may be associated with potentially serious side effects. Symptoms such as dry, scaly skin (xerosis) caused by, for example, atopic dermatitis (eczema) can be treated using a skin lotion containing sodium hyaluronate as an active ingredient. In some cancers, hyaluronan levels correlate with malignancy and poor prognosis. Hyaluronic acid is thus often used as a tumor marker to detect prostate cancer and breast cancer. The substance can also be used to monitor disease progression. Hyaluronic acid can also be used post-operatively to promote tissue healing, especially after cataract surgery. Current models of wound healing suggest using larger hyaluronic acid polymers in the early stages of healing to physically make room for white blood cells to mediate the immune response. Hyaluronic acid is also used in the synthesis of biological scaffolds for wound healing. These scaffolds typically contain proteins such as fibronectin attached to hyaluronic acid to facilitate cell migration into the wound. This is especially important for people with diabetes and chronic wounds. In 2007, the EMA extended its approval of Hylan GF-20 for the treatment of osteoarthritis pain of the ankle and forearm.
Functions
Until the late 1970s, hyaluronic acid was considered a “sticky” molecule, a common carbohydrate polymer and part of the extracellular matrix. Hyaluronic acid is the main component of synovial fluid, which increases the viscosity of the fluid. Along with lubricin, hyaluronic acid is one of the main lubricating components of the liquid. Hyaluronic acid is an important component of articular cartilage, where it serves as a coating around each cell (chondrocyte). When aggrecan monomers bind to hyaluronic acid in the presence of protein, large, highly negatively charged aggregates are formed. These aggregates absorb water and are responsible for the elasticity of the cartilage (its resistance to compression). The molecular weight (size) of hyaluronic acid in cartilage decreases with age, but its amount increases. Hyaluronic acid is also the main component of the skin and is involved in tissue repair processes. When the skin is overexposed to UVB rays, it becomes inflamed (sunburned) and cells in the dermis stop producing large amounts of hyaluronic acid and increase the rate of its degradation. After ultraviolet irradiation, hyaluronic acid degradation products accumulate in the skin. Present in abundance in the extracellular matrix, hyaluronic acid also affects tissue hydrodynamics, cell movement and proliferation, and is involved in a number of cell surface receptor interactions, including essential receptors, CD44 and RHAMM. CD44 stimulation is widely used as a marker of cell activation in lymphocytes. The effects of Hyaluronan on tumor growth may be due to its interaction with CD44. The CD44 receptor is involved in cell adhesion mediated interactions with tumor cells. Although hyaluronic acid binds to the CD44 receptor, there is evidence that HA degradation products transduce their inflammatory impulse through toll-like receptor 2 (TLR2), TLR4, or both TLR2 and TLR4 into macrophages and dendritic cells. Toll-like receptor and hyaluronic acid play an important role in the formation of innate immunity. High concentrations of hyaluronic acid in the brains of baby rats, and lower concentrations in the brains of adult rats, suggest that HA plays an important role in brain development.
Structure
The properties of HA were first established in 1930 in the laboratory of Karl Meyer. Hyaluronic acid is a polymer of disaccharides that are found in D-glucuronic acid and DN-acetylglucosamine, linked through alternating β-1,4 and β-1,3 glycosidic bonds. Hyaluronic acid can be made up of 25,000 repeating disaccharide units in length. HA polymers can vary in size from 5,000 to 20,000 thousand Da in natural conditions. The average molecular weight of hyaluronic acid in human synovial fluid is 3-4 million Da, and the molecular weight of hyaluronic acid isolated from human umbilical cord is 3,140,000 Da. Hyaluronic acid is an energetically stable substance, in part due to the stereochemistry of its constituent disaccharides. The bulky groups in each sugar molecule are in spatially favored positions, while the smaller hydrogen atoms occupy less favorable axial positions.
Biological synthesis
Hyaluronic acid is synthesized by a class of integral membrane proteins called hyaluronic synthases, three types of which are present in vertebrates: Has1, HAS2, and HAS3. These enzymes gradually lengthen gualuronan by alternately adding N-acetylglucosamine and glucuronic acid as it is expelled through the ABC transporter and through the cell membrane into the extracellular space. The synthesis of hyaluronic acid is inhibited by 4-methylumbelliferone (hymecromone, heparvit), a derivative of 7-hydroxy-4-methylcoumarin. This selective inhibition (without inhibition of other glycosaminoglycans) may be useful in preventing metastasis of malignant tumor cells. Recently, genetically modified (GMO) Bacillus subtilis has been developed to produce HA as a patented product suitable for human consumption.
Cellular receptors for hyaluronic acid
Currently, cellular GC receptors are divided into three main groups: CD44, receptor for HA-mediated motility (RHAMM), and intercellular adhesion molecule-1. CD44 and ICAM-1 were already known cell adhesion molecules with other established ligands before their binding to HA was discovered. The CD44 receptor is widely distributed throughout the body. A formal demonstration of HA-CD44 binding was proposed by Aruffo et al in 1990. Today, CD44 is recognized as the main cell surface receptor for HA. CD44 mediates the interaction of cells with GC and the coupling of the two functions as an important part in various physiological functions such as cell aggregation, migration, proliferation and activation; cell-cell and cell-substrate adhesion; endocytosis of GC, which leads to GC catabolism in macrophages, etc. Two significant roles for CD44 in skin processes have been proposed by Kaya et al. The first is to regulate keratinocyte proliferation in response to extracellular stimuli, and the second is to maintain local GC homeostasis. ICAM-1 (intercellular adhesion factor 1) is known primarily as a cell surface metabolic receptor for HA, this protein may be primarily responsible for the clearance of GC from lymph and blood plasma, and may account for the majority of total GC metabolism in the body. . Thus, ligand binding of a given receptor triggers a highly coordinated cascade of events that includes the formation of an endocytic vesicle, its association with primary lysosomes, enzymatic cleavage to monosaccharides, active transmembrane transport of these sugars in cell sap, phosphorylation of aspartic acid, and enzymatic acetylation. ICAM-1 may also serve as a cell adhesion molecule, and the association of GC with ICAM-1 may contribute to the control of ICAM-1-mediated inflammatory activation.
Split
Hyaluronic acid is broken down by a family of enzymes called hyaluronidases. There are at least seven types of hyaluronidase enzymes in the human body, some of which are tumor suppressors. The breakdown products of hyaluronic acid, oligosaccharides and HA with very low molecular weight, exhibit proangiogenic properties. In addition, recent studies have shown that hyaluronic acid fragments can induce inflammatory responses in macrophages and dendritic cells at the site of damaged tissue and grafted skin.
Action
Wound healing
The skin provides a mechanical barrier to the external environment and acts to prevent the entry of infectious agents. Damaged tissue is susceptible to infection; therefore, rapid and effective treatment is critical to reconstruct barrier function. Skin wound healing is a complex process and involves many interacting processes mediated by hemostasis and the release of platelet factors. The next stages are: inflammation, formation of granulation tissue, epithelialization and reconstruction. HA likely plays a multifaceted role during these cellular and matrix processes. HA has been suggested to play a role in the healing of skin wounds.
Inflammation
Many biological factors such as growth factors, cytokines, eicosanoids, etc. are generated during inflammation. These factors are essential in subsequent stages of wound healing because they are responsible for the migration of inflammatory cells, fibroblasts and endothelial cells at the wound site. At the beginning of the inflammatory phase of the wound healing process, the damaged tissue is saturated with HA. This is likely a reflection of increased GC synthesis. HA acts as a stimulant in the early stages of inflammation and is critical in the healing process of all damaged tissue. To improve cellular infiltration, GC was observed in a mouse air sac model (preclinical studies; a cavity is created in the dorsal region of mice using subcutaneous injection of sterile air) of carrageenan/IL-1-induced inflammation. Kabashi and colleagues showed a dose-dependent increase in the production of the proinflammatory cytokines TNF-α and IL-8 by human uterine fibroblasts at HA concentrations ranging from 10 μg/ml to 1 mg/ml through a CD44-mediated mechanism. Endothelial cells, in response to inflammatory cytokines such as TNF-α, and bacterial lipopolysaccharides, also synthesize HA, which facilitates the primary adhesion of cytokine-activated lymphocytes expressing the GC-linked species CD44 under laminar and static flow conditions. It is interesting to note that HA has opposing dual functions in the inflammatory process. Not only can it promote inflammatory healing as stated above, but it can also induce a mild inflammatory response that can help stabilize the granulation tissue matrix.
Granulation and organization of granulation tissue matrix
Granulation tissue is a perfused, fibrous connective tissue that replaces the fibrin clot during wound healing. It usually grows from the base of the wound and can fill a wound of almost any size. HA is present in abundance in the granulation tissue matrix. The diversity of cell functions that is essential for tissue repair can be attributed to the GC-rich network. These functions include promoting cell migration in the pre-wound matrix, cell proliferation, and organization of the granulation tissue matrix. Initiation of inflammation is critical for the formation of granulation tissue, so the proinflammatory role of HA, as described above, also contributes to this stage of wound healing.
GC and cell migration
Cell migration is essential for the formation of granulation tissue. The early stage of granulation tissue development is mediated by a HA-rich extracellular matrix, which is considered to provide a favorable environment for cell migration within this temporary wound matrix. The role of HA in cell migration can be explained by its physicochemical properties as discussed above, as well as its direct interaction with cells. In the first scenario, HA provides an open water-containing matrix that facilitates cell migration, while in the latter case, directed migration and control of cell motor mechanisms are mediated through specific cell interactions between HA and cell surface HA receptors. As stated previously, the three major cell surface receptors for GC are CD44, RHAMM, and ICAM-1. RHAMM is more related to cell migration. It forms links with several protein kinases associated with cellular locomotion, such as extracellular regulated protein kinase (ERK), p125fak and pp60c-Src. During embryonic development, the migratory pathway through which neural crest cells migrate is rich in GA. HA is closely associated with the process of cell migration in the granulation tissue matrix, and studies suggest that cell movement can be inhibited, at least in part, by degradation of HA or by blocking HA binding to the receptor. Providing dynamic force in the cell, HA synthesis is also associated with cell migration. As a rule, HA is synthesized in the plasma membrane and released directly into the extracellular environment. This may promote hydration of the microenvironment at sites of synthesis, and is important for cell migration by promoting cell shedding.
The role of GC in regulating the inflammatory response
Although inflammation is an integral part of the formation of granulation tissue, for normal tissue repair, the inflammation process must be contained. Granular tissue is susceptible to inflammation and has a high metabolic rate mediated by the degradation of matrix enzymes and reactive oxygen metabolites, which are products of inflammatory cells. Stabilization of the granulation tissue matrix can be achieved by controlling inflammation. GC functions as an important factor in this moderating process, which is contrary to its role in inflammatory stimulation as described above. HA may protect against the harmful effects of free radicals on cells. In studies by Foshee D. and colleagues in a rat model, HA was shown to scavenge free radicals, thereby reducing the damage caused to granulation tissue. In addition to its free radical scavenging role, HA may also function in the negative feedback loop of inflammatory activation through its specific biological interactions with biological components of inflammation. TNF-α, an important cytokine generated during inflammation, stimulates the expression of TSG-6 (TNF-stimulating gene 6) in fibroblasts and inflammatory cells. TSG-6, a GC-binding protein, also forms a stable complex with serum proteinase inhibitor IαI (Inter-α inhibitor), exerting a synergistic effect on the plasmin-inhibitory activity of the latter. Plasmin is involved in the activation of the proteolytic cascade of matrix metalloproteinases and other proteins leading to inflammatory tissue damage. Thus, the action of TSG-6/IαI complexes, which may be further orchestrated by binding to GC in the extracellular matrix, may serve as a powerful negative feedback loop during mild inflammation and stabilize granulation tissue as healing progresses. In a mouse air sac model of carrageenan/IL-1 (interleukin-1β)-induced inflammation, where HA exhibited anti-inflammatory properties, reduction of inflammation could be achieved by administration of TSG-6. The result is comparable to systemic therapy with dexamethasone.
Reepithelialization
HA plays an important role in normalizing the epidermis. HA has important functions in the process of reepithelialization due to several of its properties. It serves as an integral part of the extracellular matrix of basal keratinocytes, which are the main components of the epidermis; HA serves to “cleanse” the skin of free radicals and plays a role in the proliferation and migration of keratinocytes. In normal skin, HA is found in relatively high concentrations in the basal layer of the epidermis, where proliferating keratinocytes are found. CD44 binds to GC in the basal layer of the epidermis, where it is expressed on the plasma membrane, encountering GC-rich matrix sacs. The main functions of HA in the epidermis are to maintain the extracellular space and provide an open and hydrated structure for the passage of nutrients. Tammy P. and other colleagues found an increase in HA levels in the presence of retinoic acid (vitamin A). The proposed effects of retinoic acid on photodamage and skin aging may be due, at least in part, to an increase in HA content in the skin, causing an increase in tissue hydration. It has been suggested that the free radical scavenging properties of HA contribute to solar protection, supporting the role of CD44 as a HA receptor in the epidermis. Epidermal HA also functions as a manipulator in the process of keratinocyte proliferation, which is very important for the normal functioning of the epidermis, as well as during epithelialization during tissue repair. During wound healing, HA is expressed at the edges of the wound, in the connective tissue matrix. Kaya et al showed that suppression of CD44 expression using a specific transgene results in GC deficiency and various morphological changes in basal keratinocytes and abnormal keratinocyte proliferation in response to mitogen and growth factors in animals. Decreased skin elasticity, impaired local inflammatory response, and impaired tissue repair were also observed. Their observations support an important role for HA and CD44 in skin physiology and tissue repair.
Fetal healing of wounds and scars
The absence of fibrous scars is the main sign of wound healing in the fetus. Even over longer periods, HA content in fetal wounds is higher than in adult wounds, suggesting that HA, at least in part, reduces collagen deposition and therefore leads to reduced scar formation. This suggestion is consistent with studies by West et al., which showed that GC withdrawal in adults and in the fetus during late pregnancy causes fibrotic scars.
Role in metastasis
Hyaluronic acid synthases (HAS) play a role in all stages of cancer metastasis. By producing anti-adhesive HA, GCS can allow tumor cells to free themselves from the primary tumor mass, and if HA binds to receptors such as CD44, GTPase activation can promote epithelial-mesenchymal transition (EMT) of cancer cells. During the processes of intravasation or extravasation, the interaction of GCs producing GC receptors such as CD44 and RHAMM provokes changes in cells that allow cancer cells to enter the circulatory or lymphatic systems. During movement in these systems, HA produced by GCS protects cancer cells from mechanical damage. Finally, in the formation of metastatic lesions, GCS produces GC to allow cancer cells to interact with native cells at the secondary site and produce tumor. Hyaluronidases (HAase or HYAL) also play multiple roles in the formation of cancer metastases. By helping to break down the extracellular matrix surrounding the tumor, hyaluronidases help cancer cells escape from the primary tumor mass and play an important role in invasion, allowing the breakdown of the basal lymphatic membrane or blood vessel. Hyaluronidases are involved in the creation of metastatic lesions by promoting extravasation and clearing the extracellular matrix. Finally, hyaluronidases play a key role in the process of angiogenesis. HA fragments stimulate angiogenesis and the hyaluronidases that produce these fragments. Interestingly, hypoxia also increases GC production and hyuloronidase activity. The hyaluronic acid receptors, CD44 and RHAMM, are the most extensively studied for their role in cancer metastasis. Increased CD44 expression clinically positively correlates with metastasis in a number of tumor types. CD44 affects the adhesion of tumor cells to each other and to endothelial cells, rearranges the cytoskeleton through Rho GTPase, and increases the activity of destructive enzymes of the extracellular matrix. Increased expression of RHAMM has also been clinically correlated with cancer metastasis. Mechanistically, RHAMM promotes cancer cell motility through a number of pathways, including focal adhesion kinase (FAK), MAP kinase (MAPK), PP60 (c-SRC), and GTPases. The GC-induced motility receptor may also interact with CD44 to promote angiogenesis toward metastatic disease.
Hyaluronic acid injections
Hyaluronic acid is a common ingredient in skin care products. Until recently, hyaluronic acid fillers were injected using a classic sharp hypodermic needle. The needle passed through nerves and blood vessels, causing pain and bruising. In 2009, a new technique was developed in which the skin is pierced with a sharp needle, and then a microscopic hollow needle slides under the skin without piercing it deeper.
Additives in horse breeding
Hyaluronic acid is used to treat joint problems in horses, especially during competition or heavy work. GK is prescribed for carpal and hock dysfunction, in the absence of suspicion of sepsis or fracture. Often used for synovitis associated with osteoarthritis in horses. The substance can be injected directly into the affected joint, or intravenously for less localized disorders. May cause slight heating of the ligaments when injected directly, but does not affect clinical results. When administered intra-articularly, the drug is completely metabolized in less than a week. Please note that, according to Canadian regulations, hyaluronic acid, HY-50, should not be administered to animals intended for slaughter. In Europe, however, they do not believe that this drug has any effect or affects the taste of horse meat.
Etymology
Hyaluronic acid is extracted from hylos (Greek for "vitreous humor") and uronic acid, as it was first isolated from the vitreous humor and has a high uronic acid content. The term "hyaluronate" refers to the conjugate base of hyaluronic acid. Because the molecule typically occurs naturally in a polyanionic form, it is commonly referred to as hyaluronic acid.
Story
Hyaluronic acid is found in many tissues of the body, such as skin, cartilage and vitreous body. Therefore, it is well suited to complement biomedical supplements targeting these tissues. The first biomedical HA product, Healon, was developed in the 1970s and 1980s. Pharmacia, and was intended for use in eye surgery (namely, corneal transplantation, cataract surgery, glaucoma, and retinal detachment surgery). Other biomedical companies also produce brands of HA for use in eye surgery. The original hyaluronan has a relatively short half-life (as shown in experiments on rabbits), so various production technologies have been developed to increase the chain length and stabilize the molecule for medical use. Methods used include the introduction of protein-based cross-links, the introduction of free radical scavenging molecules such as sorbitol, and minimal stabilization of the HA chains using chemical agents such as stabilized non-animal hyaluronic acid. In the late 1970s, intraocular lens implantation was often accompanied by severe corneal edema due to damage to endothelial cells during surgery. It was apparent that a viscous, clear, physiological lubricant was required to prevent such scraping from the endothelial cells.
Research
Due to its high biocompatibility and presence in the extracellular matrix of tissues, hyaluronic acid is becoming popular as a biomaterial in tissue engineering research. In particular, a number of research groups have discovered the special properties of hyaluronic acid in the field of tissue engineering. This additional feature allows researchers to formulate the desired shape as well as reproduce therapeutic molecules. Hyaluronic acid can be created by the addition of thiols (trade name: Extracel, HyStem), methacrylates, hexadisyl amides (trade name: Hymovis), and tyramines (trade name: Corgel). Hyaluronic acid can also be created directly from formaldehyde (trade name: Hylan-A) or from divinyl sulfone (trade name: Hylan-B). Due to its ability to regulate angiogenesis by stimulating endothelial cell proliferation, hyaluronic acid can be used to create hydrogels to study vascular morphogenesis. These hydrogels have properties similar to human soft tissues but are also easily controlled and modified, making HA a very suitable substance for tissue engineering research. For example, HA hydrogels are used to reconstitute vasculature from endothelial progenitor cells using appropriate growth factors such as VEGF and Ang-1 to promote proliferation and vasculature formation. These gels exhibit a vacuole (small cavity) and lumen formation, followed by branching and growth through hydrogel degradation and ultimately forming a complex network construct. The ability to generate vascular networks using HA hydrogels leads to the possibility of clinical application of HA. In an in vivo study, when HA hydrogel with endothelial colony-forming cells was implanted into mice three days after hydrogel formation, the replicated vasculature engrafted within 2 weeks of implantation. This indicates the viability and functionality of the vasculature.
Buy hyaluronic acid
Hyaluronic acid is a fairly important component that is part of connective tissue, and is also found in biological fluids (in particular, synovial fluid) and is produced by hyaluronate synthetases (a class of membrane proteins). Hyaluronic acid is a transdermal delivery system for many other active ingredients necessary for healthy facial skin. There are a lot of drugs on the market containing hyaluronic acid as a component and used in cosmetology and medicine.
Hyaluronic acid– a natural polysaccharide of animal origin. Widely distributed in nature, it is found in the ground substance of many types of connective and nervous tissue (skin, ligaments, umbilical cord, heart valves, vitreous body of the eye, cornea, etc.) and biological fluids (saliva, synovial and articular fluid, etc.). In the connective tissue of the dermis, hyaluronic acid is located between collagen and elastin fibers, in the cells of the stratum corneum - in corneocytes.
Thus, hyaluronic acid is one of the main components of the extracellular matrix. Takes a significant part in cell proliferation and migration. Produced by some bacteria (for example, Streptococcus ).
The amount of hyaluronic acid in various sources can be up to 5% of tissue dry weight. The body of a 70 kg person on average contains ~15 g of hyaluronic acid.
Receipt
In industry, hyaluronic acid is produced in two ways: physical-chemical and biotechnological.
Physico-chemical method. Using this method, hyaluronic acid is obtained mainly from rooster combs, human umbilical cords and cattle eyes. The technological scheme for obtaining hyaluronic acid from the above-mentioned biomass includes the following stages: enzymatic digestionconnective tissue with the release of hyaluronic acid or extraction hyaluronic acid from biomass with dilute solutions of alkali or acid, subsequent specific fractionation of the isolated product to remove protein and lipid components, several stages of purification, precipitation and drying.
Recently, hyaluronic acid has increasingly been produced in a more cost-effective manner. biotechnologically from plant raw materials (wheat substrate) using bacterial cultures ( Streptococcus zooepidermicus or Streptococcus equi). The stages of obtaining hyaluronic acid using biotechnology are as follows: strictly controlled biosynthesis hyaluronic acid bacterial cells(bacteria multiply and are placed in a fermentation tank, where they synthesize hyaluronic acid under special conditions); isolation of accumulated hyaluronic acid from bacteria and its further purification; precipitation and drying. All processes of biotechnological production of hyaluronic acid are carried out under conditions of constant bacteriological and rheological control, ensuring high quality of the resulting product and, most importantly, the specified molecular weight of hyaluronic acid.
Chemical structure and molecular structure
Hyaluronic acid– non-sulfonated glycosaminoglycan. Under natural conditions, hyaluronic acid is synthesized by a class of embedded membrane proteins called hyaluronate synthetases. Vertebrates contain three types of hyaluronate synthetases: HAS1, HAS2 and HAS3. These enzymes are thought to connect molecules glucuronic acid And N -acetylglucosamine in strictly alternating order.
The structural formula of a fragment of the hyaluronic acid macromolecule is shown in Fig. 1. Macromolecular chains are built from alternating units of residues β- D -glucuronic acid And β- N -acetylglucosamine related β-(1→4)- And β-(1→3)-glycosidic bonds.
Hydrogen atoms of COOH groups of some elementary units β- D-glucuronic acid can be replaced by Na or K. Such polysaccharides are called sodium or potassium salt of hyaluronic acid ( sodium hyaluronate or potassium hyaluronate).
The elementary repeating unit of the hyaluronic acid macromolecule is the disaccharide fragment. As an example, Fig. 2 shows the elementary unit of the macromolecule of the sodium salt of hyaluronic acid
The most energetically favorable conformation of the elementary unit of the hyaluronic acid molecule is the chair conformation C1 (Fig. 3).
Bulk substituents on the pyranose ring are located in sterically favorable equatorial positions, and smaller hydrogen atoms occupy less favorable axial positions.
Due to the presence of β-(1→3)-glycosidic bonds, the macromolecule of hyaluronic acid, numbering several thousand monosaccharide residues, takes on a helix conformation (Fig. 4).
There are three disaccharide blocks per turn of the helix. The hydrophilic carboxyl groups of glucuronic acid residues located on the outer side of the helix can bind Ca 2+ ions.
Hyaluronic acid (HA), also known as (acid salt) or hyaluronan (a unifying designation for an acid and its salt), is an anionic natural polysaccharide (a non-sulfonated simple glycosaminoglycan), which is an important component of nervous, epithelial, connective tissues and the main ingredient of the extracellular matrix.
Hyaluronic acid is also part of many biological fluids inherent in living organisms (synovial fluid, saliva, etc.). This substance can be produced by certain bacteria (for example, streptococci ) and excreted from animal organs (rooster comb, vitreous body and cartilaginous tissue of cattle).
A human body weighing about 70 kilograms contains on average about 15 grams of this endogenous acid, a third of which is converted (broken down or synthesized) every day.
Structure and structure
The structural diagram of HA is characteristic of a linear polysaccharide, consisting of alternating residual parts N-acetyl-D-glycosamine And D-glucuronic acid, sequentially connected by β-1,3 and β-1,4 glycosidic bonds.
One molecule of this acid can include up to 25 thousand similar disaccharide units. HA of natural origin has a molecular weight varying between 5000-20000000 Da. In humans, the average molecular weight of the polymer found in the synovial fluid is 3,140,000 Da.
The acid molecule is energetically stable, including due to the stereochemistry of the disaccharides included in its composition. In the pyranose ring, bulky substituents are located in sterically favorable positions, while smaller hydrogen atoms are located in less favorable axial positions.
Education: Graduated from Vinnitsa National Medical University named after. N.I. Pirogova, Faculty of Pharmacy, higher pharmaceutical education – specialty “Pharmacist”.
Experience: Work in the pharmacy chains "Konex" and "Bios-Media" with the specialty "Pharmacist". Work as a Pharmacist in the Avicenna pharmacy chain in the city of Vinnitsa.
Comments
By the way, I also take hyaluronic acid in a tablet. By the way, Evalar is good, yes, but the effect is cumulative, you need to drink it for 2 months and don’t forget
There were many problems with the skin: it peeled, cracked, and wrinkles began to appear. Because of this, I decided to try hyaluronic acid in tablets, but I ended up taking it. I have already completed 6 courses, my skin has become much better, even the cold is no longer a problem.
Thanks for the good article. I myself have been taking hyaluronic acid for a long time. I tried both cream and injections, but settled on tablets. I think that this is still the most practical thing that has been created.