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<hr />Olga Zabnenkova – Candidate of Medical Sciences, Professor of the Institute of Postgraduate Education of RUDN University, Head of the Department of Cosmetology and Plastic Surgery of MS DETAL LLC (Russia, Moscow); Lyudmila Kamelina is a dermatocosmetologist at the Danishchuk Clinic, a trainer at Fitogen (Russia, Moscow).<hr /> Clinical signs of age-related changes are characterized mainly by atrophic processes affecting not only epidermal-dermal structures, but also subcutaneous fatty tissue, muscle, and bone tissue. Modern anti-age therapy includes systemic (hormone replacement, antioxidant, etc.), injection (botulinotherapy, contour plastic), physiotherapeutic methods of restorative treatment (microcurrent, IPL therapy, RF technologies, etc.). Despite the huge selection of “anti-aging” cosmetic procedures, one of the most physiological and safe methods of restoring the structure of the skin and the volume of subcutaneous fat is the use/introduction of exogenous hyaluronic acid. Native (unmodified) hyaluronic acid is used for the biorevitalization method, and stabilized or reticulated hyaluronic acid is used for bioreinforcement, injection and volumetric contouring. Features of hyaluronic acid Hyaluronic acid is a polysaccharide consisting of alternating structural units represented by a compound of glucuronic acid and N-acetylglucosamine. In 1934, Karl Meyer and his assistant John Palmer described the process of isolating a new substance, glycosaminoglycan, from the vitreous humor of the cow&#39;s eye. This was the birth of one of the most versatile and fascinating macromolecules in nature. The number of repetitions of disaccharides in the complete structure of the molecule can reach 10,000 or more, which amounts to a molecular weight of ~4 million daltons (each disaccharide molecule has a mass of ~400 daltons). The average length of a disaccharide molecule is ~1 nm. Thus, if a hyaluronic acid molecule from 10,000 repeats is stretched into one line, it can reach a length of 10 μm, which is approximately equal to the diameter of a human red blood cell.<blockquote> In the dermis, hyaluronic acid is synthesized by fibroblasts with the help of hyaluronate synthase enzymes, and is destroyed in the intercellular space with the participation of hyaluronidase enzymes and when hyaluronic acid is exposed to free radicals formed as a result of oxidative processes. There is also evidence of the synthesis of hyaluronic acid by epidermal corneocytes.</blockquote> The dermis is characterized by hyaluronic acid weighing on average 2 million daltons, with a half-life of 2 days, while in the epidermis the half-life is 1 day. Synthesized under the fibroblast membrane, hyaluronic acid enters the intercellular space, where it immediately begins to curl into a spiral. The hyaluronan molecule takes the form of a coil in physiological solutions, which occupies a fairly large domain. The actual mass of hyaluronan within this domain is very low - ~0.1% (wt/vol) or less if the macromolecule is in low concentration saline solution. This means that domains of individual molecules will overlap each other at concentrations of 1 mg of hyaluronan per ml or higher. Small molecules, such as water molecules, electrolytes and nutrients, can diffuse freely within the domain boundaries. However, large molecules, such as protein molecules, are partially excluded from the domain due to their hydrodynamic size in solution.<blockquote> Hyaluronic acid attracts water, osmotically active electrolytes, proteins, polysaccharides, and enzymes well. And therefore it is an important component of the intercellular matrix.</blockquote> Studies have shown that there are receptors specific to hyaluronic acid on cell membranes. The presence of these receptors indicates the “interest” of a given cell in hyaluronic acid. CD44 receptors located on the membranes of fibroblasts and keratinocytes have been well studied. The connection of HA with the CD44 receptor on the fibroblast membrane increases the activity of this cell, increasing the synthesis of components of the intercellular matrix, including collagen, elastin and, to a greater extent, hyaluronic acid. In epithelial tissues of an adult, CD44 receptors and hyaluronic acid are present in large quantities in the keratinizing epithelium and are absent in the single-layer non-keratinizing epithelium. CD44 receptors are markers of epidermal growth and normal differentiation of epidermal cells. Another known receptor involved in the interaction of cells with external hyaluronic acid is the receptor for hyaluronan-mediated motility (RHAMM). RHAMM ensures an increase in the quality of epithelization in an environment rich in hyaluronic acid, and the migration of cells to the site of inflammation in the dermis, where the breakdown of hyaluronic acid is activated. Vascular endothelial cells have ICAM receptors, the connection of which with hyaluronic acid causes activation of vascular endothelial cells and leads to the growth of new capillaries.<blockquote> Another important function of hyaluronic acid is to protect DNA from oxidants.</blockquote> The protective mechanism of HA may involve either the capture of iron ions and thereby suppression of the Fenton reaction, as a result of which secondary oxidants are formed; and/or the action of HA as an antioxidant, directly removing primary and secondary reactive oxygen messengers during the decomposition of HA itself. Consequently, hyaluronic acid is a consumable antioxidant and during periods of oxidative stress, which are sun exposure, illness, etc., the dermis, first of all, experiences a lack of hyaluronic acid. Biorevitalization method The idea of introducing unmodified high molecular weight hyaluronic acid into the skin belongs to Professor A. Di Pietro (Milan 2001). He formulated the definition of biorevitalization as “a method of intradermal injections of unmodified hyaluronic acid, allowing to achieve restoration of the physiological environment and normalization of metabolic processes in the dermis, as a result of which the aesthetic effect is prolonged and enhanced over time due to the restoration of the tissue’s own properties.” Breaking down under the influence of hyaluronidases, hyaluronic acid exists in the form of molecules with different molecular weights. And the biological functions of HA molecules directly depend on their molecular weights.<table border="1" cellpadding="1" cellspacing="1"><tbody><tr><td> GK chain length</td><td> Properties</td></tr><tr><td> Long HA chains with a mass greater than 500 kDa</td><td> The extracellular matrix is formed. Suppress the activity of fibroblasts and macrophages. They have a pronounced anti-inflammatory and antioxidant effect.</td></tr><tr><td> Short chains of HA with a mass of 200-100 kDa</td><td> Stimulate cell migration and proliferation. Stimulates the synthesis of hyaluronic acid.</td></tr><tr><td> Oligosaccharides with a mass less than 100 kDa</td><td> Additionally: - stimulate angiogenesis; - have an immunomodulatory effect; - increase the survival rate of fibroblasts; - stimulate proliferation of stem cells.</td></tr></tbody></table> Table 1. Biological functions of hyaluronic acid molecules with different molecular weights (Stern R, 2006) The main indications for biorevitalization are:<ul><li> skin dehydration of various origins, caused by both hormonal changes, unfavorable meteorological conditions, and improper cosmetic care, etc.;</li></ul><ul><li> decrease in turgor caused by a deficiency of endogenous glycosaminoglycans as a result of a decrease in the synthetic activity of fibroblasts;</li></ul><ul><li> photoinduced aging, characterized by hyperkeratosis and hyperpigmentation, chronic inflammation, increased activity of metalloproteases, etc.</li></ul> Currently, the indications for the administration of unmodified HA are expanding and are no longer limited only to clinical signs of dehydration, decreased tone, etc. In our practice, we widely use this technique to reduce the reparative period after chemical peeling procedures, fractional photothermolysis and other skin resurfacing, to increase efficiency physiotherapeutic anti-age methods (photo- and RF-therapy), in the complex treatment of atrophic (post-acne) skin scars. The choice of drugs containing native hyaluronic acid is quite wide (Table 2).<table border="1" cellpadding="1" cellspacing="1"><tbody><tr><td> Name</td><td> Molecular mass</td><td> HA content (mg/ml (%))</td></tr><tr><td> Achyal</td><td> 1000 kDa</td><td> 10.0 (1%)</td></tr><tr><td> Surgilift</td><td> 2500 kDa</td><td> 13.5 (1.35%)</td></tr><tr><td> Ial-System</td><td> 1000 kDa</td><td> 18.0 (1.8%)</td></tr><tr><td> Ial-ACP</td><td> More than 1000 kDa</td><td> 20.0 (2.0%)</td></tr><tr><td> Teosyal meso</td><td> 1000 kDa</td><td> 15.0 (1.5%)</td></tr><tr><td> Mesolis</td><td> 1000 kDa</td><td> 14.0 and 18.0 (1.4% 1.8%)</td></tr><tr><td> Viscoderm</td><td> 1000 kDa</td><td> 8.0 (0.8%) 16.0 (1.6%) 20.0 (2.0%)</td></tr></tbody></table> Table 2. Preparations created on the basis of native HA for the biorevitalization technique. Features of biorevitalization<ul><li> Biological and photoinduced aging</li></ul> The introduction of native hyaluronic acid is carried out primarily to prevent involutional changes. The biorevitalization method can also be recommended for patients in case of oxidative stress, for preparing the skin before sun exposure and recovery after it. This is because hyaluronate reduces inflammatory responses by inhibiting lipid peroxidation that occurs as a result of oxidative stress. Thus, biorevitalization acts as a kind of “airbag”. Additionally, active prolonged hydration is achieved.<blockquote> The course of treatment ranges from 4-6 sessions with a frequency of 1 time in 2-3 weeks, administration technique: papular, linear-retrograde.</blockquote> It must be remembered that in patients with skin phototypes IV-VI (according to Fitzpatrick), if the biorevitalization method is carried out in the spring-summer period, it is necessary to use sunscreen (SPF no less than 30, PPD no less than 10), avoid sun exposure immediately after the procedure and during the next 2-3 days. Otherwise, an inflammatory reaction in the skin at the injection sites can lead to the formation of hyperpigmentation. At the same time, in our clinical practice we rarely use the biorevitalization method in the form of monotherapy. When correcting clinically diagnosed involutional skin changes (patients over 35 years old), we recommend the biorevitalization method to potentiate the clinical effect of physiotherapeutic techniques. Thus, in patients with thin skin and a finely wrinkled type of aging, the combination of RF technologies (radio wave lifting) and the introduction of native HA is optimal. Hydration of the epidermis and dermis increases the permeability of tissues to electric current, thereby improving uniform heating of tissues and protein denaturation, which allows reducing both the number and frequency of RF therapy sessions. If telangiectasias and hyperpigmentation predominate in the clinical picture, in addition to biorevitalization, additional phototherapy (IPL technology) is recommended, aimed at stimulating the dermis with damage to superficially located dilated vessels and destruction of unevenly deposited pigment.<blockquote> The synergy of these two techniques is especially important in the correction of photo-induced skin aging. Since the stimulating effect of phototherapy is based on the fact that photons of light emitted by the device’s LED activate a number of components of the mitochondrial respiratory chain.</blockquote> Thus, the primary infrared photoreceptor is cytochrome oxidase, which activates the mitochondrial respiratory chain, thereby increasing ATP production. The mechanism by which hyaluronic acid creates an environment favorable for cell activity, as well as its antioxidant effect, potentiate the effect of phototherapy. Biorevitalization and photorejuvenation procedures are carried out at intervals of 2 weeks, the course is 3-4 sessions.<blockquote> For patients with thick, porous skin and deep wrinkles, the combination of biorevitalization with fractional non-ablative laser skin damage (fractional photothermolysis) is optimal.</blockquote> Laser radiation with a wavelength of 1550 nm causes coagulation of the epidermis and dermis at a depth of up to 1.5 mm. The stratum corneum of the epidermis is not damaged, thereby maintaining barrier functions. The release of proteolytic enzymes triggers remodeling processes in the intact areas of the dermis surrounding the microthermal treatment zones. Stress mediators in the area surrounding the coagulation zone initiate the metabolic activity of fibroblasts and other cells of the dermal matrix, which leads to activation of the synthesis of the structural components of the dermis - collagen and elastin, and neovascularization. The essence of remodeling induced by fractional photothermolysis is that, simultaneously with the synthesis of new tissue at the site of the damaged tissue, the cellular elements surrounding the damaged areas are also renewed. The fundamental difference between fractional photothermolysis and previously carried out methods of laser ablation and dermabrasion is that intact tissue is preserved around the micro-zones of damage, ensuring complete regeneration in the damaged zones. But it must be remembered that the regenerative capabilities of patients in the age group after 40-45 years decrease, this becomes especially noticeable in the menopausal period, therefore, supporting regeneration with native hyaluronic acid is indicated and necessary. Injections of hyaluronic acid on days 7-10 after the photothermolysis procedure promote faster removal of necrotic debris from the surface of the epidermis, eliminate dryness and flaking, activate reparative processes, and restore skin turgor.<ul><li> Post-acne</li></ul> Post-acne correction is usually not difficult. Depending on the area, localization of the lesion, the severity of scar changes, it is possible to carry out median chemical peeling or microcrystalline, laser resurfacing, fractional photothermolysis, dermabrasion, etc. In the case of stamped, spear-shaped atrophic scars, in addition to the above methods, it is recommended to introduce hyaluronic acid into the atrophy zone, under the scar with preliminary separation of the area of scar deformation from the underlying tissues. Preparations in a volume of 0.01-0.03 ml are administered directly under the atrophic scar using a papular technique with hypercorrection, the injection depth is 2-3 mm. To separate the area of atrophy from the underlying tissue, it is possible to use a 27 G needle or a linear scalpel. This technique stimulates the raising of the “bottom” of the scar due to mechanical damage to the fibrous cords in the dermis. And the introduction of hyaluronic acid promotes neocollagenesis in the atrophy zone, accelerating the smoothing of scar deformities. Reaction to the introduction of biorevitalizing materials Immediately after injection, erythema may be observed in the area where the materials are introduced, which is transient (no more than 1 hour). When injecting into the periorbital zone, due to the high hydrophilicity of the drugs, swelling may occur. The swelling goes away on its own within 2-3 days after the procedure. Patients with swelling in the eyelid area need to reduce the dosage regimen of the drug. Hematomas are possible when performing linear injections in the lower third of the face and when performing microinjections into the reticular layer of the dermis. If there are signs of a hematoma, it is necessary to apply compression by pressing with a finger for 2-3 minutes. Individual hypersensitivity to the components of the drug is an extremely rare phenomenon. In the event of an allergic reaction (in particular, urticaria), antihistamines should be prescribed for 2-3 days. Corticosteroid ointments may be used. It is important to carefully collect anamnesis before the procedure to identify contraindications to its implementation. First published: KOSMETIK international journal, No. 3 (41), 2010

Biorevitalization: opportunities in the practice of a cosmetologist