The use of preparations based on hyaluronic acid modified with amino acids and preparations based on micronized collagen in injection cosmetology

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INTRODUCTION

Skin health and beauty are key factors reflecting overall well-being and perception of health in humans. The condition of the skin often affects emotional state, quality of life, and social interactions [1]. Correction of age-related skin changes remains one of the most relevant challenges in modern aesthetic medicine [1, 2]. Skin aging is a long-term multifactorial process involving transformation of tissue and cellular homeostasis, impaired proteostasis, decreased immunity, impaired DNA repair, and other pathological processes [1]. According to research, the number of aesthetic procedures aimed at correcting age-related skin changes has been steadily increasing worldwide [1–10]. In modern minimally invasive (injectable) aesthetic medicine, one of the most effective methods of aesthetic correction is the use of hyaluronic acid in combination with amino acids [2–10].

Hyaluronic acid is a natural linear unmodified heteropolysaccharide consisting of regularly alternating residues of D-glucuronic acid and N-acetyl-D-glucosamine linked by β-glycosidic bonds [1–5]. The highest content of hyaluronic acid in the human body is found in the skin (about half of the total body hyaluronic acid), synovial fluid, and vitreous body. Injectable hyaluronic acid is characterized by a relatively low risk of adverse events [5, 6]. Age-related skin changes such as wrinkles and laxity are largely associated with structural alterations in the dermis, particularly fragmentation and disorganization of collagen fibers [3]. Collagen is the principal protein of the dermal matrix, responsible for structural, protective, and metabolic functions of the skin. In combination with hyaluronic acid, it forms an organized extracellular matrix essential for cellular homeostasis [7].

Various modern methods of aesthetic correction of age-related skin changes are aimed at activation of neocollagenesis and subsequent dermal remodeling [2, 3]. Currently, techniques aimed at stimulating neocollagenesis are a leading focus in modern anti-aging therapy. This approach enhances skin density, improves tone and turgor, and provides a long-term lifting effect [7]. Although injectable biorestructuring methods are well-established in aesthetic medicine, several issues remain unresolved, particularly concerning the efficacy and durability of clinical effects of various anti-aging therapies [1].

The formal analysis conducted in this work was aimed at identifying modern aspects of application, efficacy, and durability of clinical effect of hyaluronic acid preparations modified with amino acids and micronized collagen preparations in aesthetic medicine.

The analysis was based on scientific publications indexed in international databases (Web of Science, Scopus, PubMed) and in the Russian Science Citation Index (RSCI). Sources were selected using the following keywords and phrases: возрастные изменения кожи (age-related skin changes) + гиалуроновая кислота (hyaluronic acid) + аминокислоты (amino acids) + инъекции (injections) + препараты на основе микронизированного коллагена (preparations based on micronized collagen). The search depth was 10 years (2014–2024).

When selecting Russian sources, preference was given to studies published in journals included in the RSCI core. When selecting foreign publications, preference was given to journals indexed in Web of Science and Scopus.

A bibliographic search using the keyword phrase возрастные изменения кожи и инъекции гиалуроновой кислоты (age-related skin changes and hyaluronic acid injections) identified 3892 foreign and 1770 Russian publications. Further search of foreign sources using the keyword phrases возрастные изменения кожи, гиалуроновая кислота, аминокислоты, инъекции (age-related skin changes, hyaluronic acid, amino acids, injections) yielded 923 publications.

In the RSCI database for 2014–2024, the number of publications using the keyword phrase возрастные изменения кожи + гиалуроновая кислота (age-related skin changes + hyaluronic acid) was 843, and using возрастные изменения кожи, гиалуроновая кислота, аминокислоты, инъекции (age-related skin changes, hyaluronic acid, amino acids, injections) was 163. For writing this analytical review, 46 sources for the last 10 years were selected. Thus, our search revealed a steadily growing interest, both globally and in Russia, in the use of hyaluronic acid modified with amino acids and micronized collagen preparations in aesthetic medicine.

Study of the efficacy of modified hyaluronic acid and micronized collagen preparations in aesthetic medicine: analysis of russian and international sources

Mechanism of Action of Modified Hyaluronic Acid and Micronized Collagen Preparations

A significant portion of the total body collagen (approximately 40%) is located in the skin, with type I collagen being the main protein of the dermis (types III and V are present in much smaller amounts) [7]. Collagen accounts for up to 70% of the dermis’ dry weight and gradually decreases with age [7, 8]. The average physiological concentration of hyaluronic acid in the dermis is approximately 0.05 mg/mL, ranging 0.01–0.5 mg/mL [9]. Hyaluronic acid participates in the formation of collagen protofibrils and microfibrils during their integration into fibrils, resulting in the formation of mature collagen fibers [5–7, 9, 10]. Normal levels of hyaluronic acid are responsible for physiological skin turgor and tone, the absence of wrinkles, and a healthy complexion [9]. With age (around 30–35 years), fibroblast activity decreases, which in turn reduces hyaluronic acid synthesis. Injectable hyaluronic acid not only provides exogenous delivery to the skin but also stimulates fibroblast-mediated hyaluronic acid production [9, 11]. In the dermis, hyaluronic acid exists in a protein-bound form as sodium hyaluronate (hyaluronan) [9–12]. Macromolecules of proteins and polysaccharides form a structured three-dimensional system (extracellular matrix) that performs multiple functions: maintaining skin shape and strength, providing mechanical properties, barrier and protective functions, dermal homeostasis, cell migration and regulation of intercellular interactions, resistance to damage and deformation, and support of water, protein, and carbohydrate metabolism.

Hyaluronic acid combined with other compounds, such as amino acids or vitamins, is actively used for skin aging correction as an effective biorevitalizing agent [7, 9–25]. Biorevitalization enhances fibroblast synthetic activity by restoring an optimal physiological environment, thereby stimulating the synthesis of collagen, elastin, and hyaluronic acid [1]. The unique physicochemical properties of hyaluronic acid molecules are critical: at physiological pH, this anionic heteropolysaccharide can bind large amounts of water, thousands of times its own weight [9, 10]. Degradation of high-, medium-, and low-molecular-weight hyaluronic acid activates fibroblasts and induces elastin and collagen (particularly type I) production [13]. Hyaluronic acid, comprising approximately 10 monomeric units (molecular weight ~50 kDa), exhibits pro-angiogenic activity by promoting endothelial cell proliferation and the formation of new capillaries, and also possesses pro-inflammatory effects [13–15]. Hyaluronic acid molecules consisting of 150–500 disaccharide units (low-molecular-weight hyaluronic acid, ~200–450 kDa) significantly accelerate fibroblast and keratinocyte proliferation. Molecules of 1500–2000 or more monomer units (high-molecular-weight hyaluronic acid, ~1000–3000 kDa) actively contribute to the formation of the dermal extracellular matrix, structural organization of the collagen network, dermal hydro-balance, and medium viscosity [13–15].

According to research, the degradation of hyaluronic acid fragments often leads to the formation of biologically active oligosaccharides with diverse properties [13, 14]. Thus, hyaluronic acid supports the maintenance of dermal structure, physiological turgor, and skin tone, whereas degradation products of hyaluronic acid stimulate endothelial cell proliferation and migration by modulating inflammatory processes and enhancing neoangiogenesis [13]. Intradermal injection of high-molecular-weight hyaluronic acid results in the formation of low-molecular-weight fragments, with the release of substantial amounts of free water entering the cells and hyaluronic acid depolymerization and neutralization of free radicals [13–15]. Intradermal injection of low-molecular-weight hyaluronic acid activates fibroblasts, enhancing the synthesis of glycosaminoglycans, collagen, and elastin, thereby improving the elastic properties of the skin [7]. The most pronounced activation of human dermal fibroblast and keratinocyte proliferation is achieved with molecules of approximately 200 kDa [7, 13–15].

Hyaluronic acid acts as a regulator of cellular proliferation and migration via receptor-mediated effects, provides skin hydration, and activates fibroblasts, whereas high-molecular-weight hyaluronic acid also exhibits antioxidant and anti-inflammatory properties [9]. In an in vitro study on fibroblast cultures, incubation with a hyaluronic acid preparation increased fibroblast viability and upregulated the expression of type I collagen and elastin genes [9].

Hyaluronic acid binds to specific cell surface receptors, stimulating intracellular signaling pathways that control cell migration [9, 10]. Its biological effects are associated with interactions with specific cell-associated receptors, including CD44 and the receptor for hyaluronan-mediated motility (RHAMM), and with enhanced synthesis of growth factors such as fibroblast growth factor 2 (FGF2) and keratinocyte growth factor (KGF) [13]. CD44 is the primary hyaluronic acid receptor, which belongs to the family of hyaladherins (proteins that bind hyaluronic acid). Hyaluronic acid, together with specialized glycoproteins and proteoglycans, forms the ground substance of the extracellular matrix [10, 14, 20]. Hyaluronic acid biosynthesis occurs at the inner surface of the plasma membrane of cells from the fibroblastic lineage [20–25].

Hyaluronic acid participates in the formation of networks of type I, III, IV, and VII collagen fibers and also acts as a signaling molecule influencing various cellular functions. During differentiation of the cellular pool, hyaluronic acid accumulates concurrently with cell migration within the extracellular matrix. It facilitates cell separation and contributes to the formation of channels with varying degrees of hydration, promoting cell migration [10–25]. It has been shown that the addition of high-molecular-weight hyaluronic acid to highly motile transformed fibroblasts sharply reduces their motility through polysaccharide binding to CD44, with the direct involvement of matrix metalloproteinases (MMP) [10–21]. MMP can cleave the hyaluronic acid-binding domain of the CD44 receptor, thereby facilitating cell migration. Metalloproteinase inhibitors block this regulatory system [20–25]. Through the same receptor, hyaluronic acid also affects apoptosis, whereas via the specific receptor RHAMM, it influences cell motility [21, 25]. Low-molecular-weight fragments of hyaluronic acid are involved in the autoregulation of its own synthesis. Specifically, high-molecular-weight hyaluronic acid elongates its polysaccharide chain by binding to hyaluronan synthase on the fibroblast cytoplasmic membrane, a process mediated by the CD44 receptor. Competitive displacement of long hyaluronic acid chains by shorter ones releases hyaluronan synthase and activates hyaluronic acid synthesis. Consequently, accumulation of high-molecular-weight hyaluronic acid limits its own synthesis, whereas fragmentation into low-molecular-weight oligosaccharides stimulates hyaluronic acid production [9, 10, 13, 14, 20–25]. Replacement of high-molecular-weight hyaluronic acid with oligosaccharides at the CD44 binding site induces the expression of genes encoding MMP, collagen, hyaladherins, and hyaluronan synthase 2 (HAS2), creating conditions for full extracellular matrix remodeling [9, 13, 14].

Intradermal injection of hyaluronic acid stimulates neocollagenesis in the skin, which is detected after one month and persisting for up to three months [24]. Concurrently, a significant increase in the expression of MMP genes and tissue inhibitors of MMP, which regulate collagen catabolism, was observed. The addition of unstabilized hyaluronic acid with a molecular weight of approximately 1200 kDa promoted maintenance of cell proliferation, de novo collagen biosynthesis, and MMP-1 activity [10, 14, 24, 25].

Hyaluronic acid reduces fibroblast apoptosis induced by various stressors (e.g., ultraviolet radiation, physical stress), whereas fibroblasts with high HAS2 gene expression show greater resistance to stress-induced apoptosis [10, 14, 24, 26, 27]. Previously, biorevitalization preparations contained only native (non-cross-linked) hyaluronic acid; however, modern formulations often combine various biocompatible bioactive components, such as vitamins, minerals, nutrients, hormones, growth factors, amino acids, autologous cultured fibroblasts, and homeopathic agents, and others [1, 7, 9–15]. It has been demonstrated that incorporating bioactive components into biorevitalization preparations enhances efficacy by increasing substrate availability for matrix component synthesis, activating signaling pathways, and other processes [1]. When hyaluronic acid preparations with added bioactive substances are used, fibroblasts acquire a more elongated morphology and an activated phenotype, leading to enhanced production of type I and III collagen, increased procollagen and MMP inhibitor levels, with positive effects maintained for 3–6 months post-injection [1, 7]. Another study also demonstrated increased synthesis of type IV collagen, elastin, and integrins in fibroblasts incubated with both cross-linked and non-cross-linked hyaluronic acid [16]. Vitamins (ascorbic acid, retinol, riboflavin, tocopherol, folic acid), amino acids (glycine, cysteine, methionine, proline, lysine), oligopeptides (glutathione, carnitine), coenzymes (coenzyme Q), and metals (Cu, Zn, Mg), covalently immobilized on the polysaccharide, are delivered into fibroblasts in a targeted manner via endocytosis during extracellular hyaluronic acid degradation along with its fragments through specific CD44 and RHAMM receptors.

Studies have demonstrated a progressive decrease in dermal collagen content with age (approximately 20% per decade after women reach 40 years) [3]. Most authors suggest that this trend is associated with suppression of the proliferative and synthetic functions of fibroblasts: with aging, the overall fibroblast pool decreases, and cells acquire a “quiescent” inactive phenotype [3, 8, 18, 22]. Concurrently with these changes, the quality of collagen fibers alters, which includes an increase in density resulting from the formation of additional covalent cross-links between polypeptide chains [3]. These structures become more resistant to MMP, which are responsible for protein catabolism and renewal; consequently, the extracellular matrix accumulates chaotically arranged fragmented collagen fibers that lose focal contacts with fibroblasts (inactive phenotype), creating a vicious cycle [3, 8, 17, 18]. Changes in collagen content within connective tissue depend on the number of resident fibroblasts and the intensity of collagen synthesis and degradation, which are mutually regulated via feedback mechanisms [17, 18].

Collagenogenesis involves several stages: ribosomal synthesis of the polypeptide chains of pre-pro-α collagen chains, their hydroxylation and glycosylation, formation of procollagen, deposition of procollagen into the extracellular matrix with removal of N- and C-terminal domains, formation of microfibrils in the extracellular space with preliminary oxidative deamination of certain lysine residues, and finally, the formation of complex fibrous structures—fibrils, fibers, and the tissue fibrous scaffold—with the participation of hyaluronic acid and proteoglycans [28–32].

Intradermal injection of collagen preparations stimulates the synthesis of type I and III collagen by altering fibroblast morphology [1]. Collagen preparations represent a distinct group of bioreparation methods due to collagen’s intrinsic ability to self-organize into fibers, providing a natural scaffold for cells and the surrounding matrix [17]. This environment increases the number of available adhesion sites for fibroblasts, resulting in a more elongated cell shape, characteristic of a younger phenotype. Type I micronized collagen suspension has been shown to stimulate normal fibroblast lines, increasing type I and III collagen levels, overexpression of proteins involved in collagen biosynthesis, maturation, and secretion, including prolyl-4-hydroxylase and heat shock protein (HSP), which stabilize the triple helix of procollagen and accelerate collagen formation and secretion [1]. Additionally, an increase in the expression of α-smooth muscle actin (α-SMA), stretching of the fibroblast plasma membrane, and formation of extracellular vesicles have been observed, which is considered indicative of the capacity to induce myodifferentiation of fibroblasts [18]. Collagen synthesis is regulated by many post-translational modifications occurring intracellularly and extracellularly. Intracellular events include post-translational hydroxylation and glycosylation, polypeptide chain association, and triple-helix folding; extracellular events include N- and C-propeptide cleavage, collagen self-assembly into fibrils, and fibril cross-linking. Prolyl-4-hydroxylase catalyzes hydroxylation of collagen proline residues, promoting collagen maturation within fibroblasts. The endoplasmic reticulum molecular chaperone HSP47 acts at multiple stages of collagen maturation: preventing aggregation and degradation of newly formed procollagen chains, accelerating triple-helix formation, stabilizing its structure, and facilitating collagen secretion [8, 18, 20, 22, 26, 27, 29]. Exogenous type I collagen derived from bovine sources significantly increases densitometric parameters, HSP47 protein expression, and P4HA1 gene levels, and induces cytoskeletal remodeling with well-organized actin filaments and cell elongation [1, 8, 18, 20, 22, 26, 27, 29–32]. Stimulation that enhances fibroblast collagen synthesis also promotes degradation of newly synthesized collagen (primarily via MMP activation). It should be noted that only mature collagen resistant to enzymatic degradation (rather than procollagen) determines the mechanical properties of the skin.

In a study of 128 cases of intradermal injection of a 7% solution of non-reconstructed type I bovine collagen, an increase in the content of neutral-salt-soluble and total collagen fractions in the skin was observed, along with enhanced collagenolytic activity, indicating activation of collagen turnover with a predominance of biosynthesis [28]. Neutral-salt-soluble collagen represents the fraction of young, newly formed fibrillar structures. An increase in this collagen fraction reflects high biosynthetic activity of dermal fibroblasts. According to research data, administration of exogenous type I bovine collagen forms a dermal matrix guiding regeneration, stimulates fibroblast functional activity, and enhances dermal hydration due to additional negative charges present on collagen molecules [7].

Current studies continue to investigate the mechanism of action of exogenous type I bovine collagen in activating neocollagenesis. It is now suggested that collagen and its fragments may accelerate skin renewal by inducing the synthesis of regulatory T cells (Tregs) and M2 macrophages (CD163-positive cells) [33]. During tissue remodeling, the proper reduction of old collagen scaffolds is of particular interest [33]. M2 macrophages play a key role in extracellular matrix remodeling, inflammation resolution, and tissue repair [33]. Through secretion of interleukin 10 (IL-10) and ornithine, M2 macrophages enhance extracellular matrix production by fibroblasts [33]. Collagen serves as a matrix for directed migration of macrophages and fibroblasts to the target area, activating chemotaxis, proliferation, and secretory activity of cell populations, particularly fibroblasts [17, 18, 28, 33].

According to current understanding, injection of preparations induces an aseptic wound-healing response at the injection site, releasing inflammatory mediators that stimulate extracellular matrix component synthesis; subsequently, fibroblast proliferation occurs, predominantly of young forms, accompanied by nerve fiber growth and macrophage-mediated resorption of heterologous collagen, with activation of a thermostable polypeptide factor that induces DNA synthesis and a new wave of fibroblast proliferation. These processes result in neocollagenesis with synthesis of endogenous collagen and formation of a new autodermal layer [33].

Following intradermal injection of a 7% unmodified bovine collagen preparation, an early increase in lactate levels, lactate/pyruvate ratio, and lactate dehydrogenase activity in the skin was observed. At the same time, hexokinase activity and glycogen content decreased. At later time points (days 21 and 37), the lactate/pyruvate ratio decreased below control values, whereas hexokinase and glucose-6-phosphate dehydrogenase activity, glycosaminoglycan content, and hyaluronic acid levels increased [34].

Hyaluronic acid preparations modified with amino acids and micronized collagen preparations affect neocollagenesis by restoring an optimal physiological environment and enhancing cellular activity, predominantly of fibroblasts, resulting in skin hydration and increased synthesis of collagen, elastin, and hyaluronic acid.

Use of Hyaluronic Acid Modified with Amino Acids and Micronized Collagen Preparations in Injectable Aesthetic Medicine

In modern aesthetic medicine, modified hyaluronic acid preparations are increasingly applied, with multiple studies confirming their high efficacy in correcting facial skin aging [7]. A study of the efficacy of lysine-enriched hyaluronic acid biorevitalizers for correction of age-related facial skin changes in 50 patients demonstrated increased secretion of various growth factors, increased skin thickness, and activation of collagen synthesis. The therapeutic effect was maintained for 12 months after the course of procedures [21]. Comparative research on intradermal injection of unmodified 0.8%, 1.6%, and 2.0% hyaluronic acid on functional skin parameters in patients of different age groups showed improvement in acid–base balance, hydration, and skin elasticity after treatment. The study demonstrated that treatment outcomes depend on appropriate selection of hyaluronic acid concentration according to the degree of decreased skin elasticity [4].

Injections of complexes of antioxidants and vitamins together with amino acids create favorable conditions for collagen molecule synthesis [7]. It is recommended to assess amino acid concentration when using mesotherapy preparations, as they may prolong the period of tissue biodegradation with longer retention of papules [7]. It was also found that the combination of the copper-binding tripeptide (GHK-Cu) and hyaluronic acid promotes synthesis of types I, IV, and VII collagen. At a 1:9 ratio, GHK-Cu and low-molecular-weight hyaluronic acid provide the most pronounced effect, significantly increasing the synthesis of type IV collagen [26].

A study evaluating the safety and efficacy of correction of involutional skin changes using stabilized hyaluronic acid preparations in 35 patients over 12 months demonstrated a more pronounced effect in the group receiving combined therapy with stabilized hyaluronic acid and biorevitalizing agents compared with the group receiving monotherapy with hyaluronic acid fillers, according to the International Global Aesthetic Improvement Scale (GAIS) at months 1, 2, 3, and 6 and by cutometry and corneometry measurements (Courage–Kazaka device, Germany) [35].

A Russian study involving 20 patients of both sexes (18 women and 2 men) aged 35–65 years with signs of facial skin aging showed that the FACE-Q Satisfaction With Skin score in the biorevitalization group using hyaluronic acid gel increased by 46.89%, and 70% of participants noted facial rejuvenation [36].

In a foreign study involving 20 men and women (mean age of 40.15 ± 6.63 years), three injections of hyaluronic acid (1–2 mL) were administered at 3-week intervals, and subsequent evaluation of skin hydration and elasticity parameters showed significant improvement [37].

A study on the efficacy of hyaluronic acid modified with amino acids in the periocular area demonstrated significant improvements in skin thickness and turgor and a reduction in the severity of dark circles and wrinkles already after the third session (after one month) [38].

Research involving 37 patients after three monthly intradermal injections of hyaluronic acid modified with a complex of amino acids showed both subjective and objective (using 3D photometric analysis) reduction in wrinkle severity and improvement in peri-oral skin condition at days 30, 60, and 180 [39]. Morphometric assessment of the efficacy and safety of intradermal hyaluronic acid in combination with several amino acids (glycine, L-proline, L-leucine, L-lysine, L-valine, and L-alanine) in women aged 30–55 years demonstrated significant improvement in hydration and skin turgor on both sides of the face [40].

A course of intradermal injections of micronized collagen contributes to rapid restoration of soft tissue volume deficit, with prolonged effect [3]. According to several researchers, within a few days after the procedure (days 2 and 4), an increase in collagen levels is associated with the presence of exogenous protein in the dermis, whereas at later time points (days 21 and 37), enhanced neocollagenesis is observed in the skin [3]. Safety and efficacy studies of collagen complexes in correcting age-related facial skin changes using clinical scales demonstrated significant improvements in skin quality and elasticity, smoothing of the skin surface, particularly in areas with fine wrinkles [3]. Ultrasound scanning also revealed increased dermal thickness and acoustic density, suggesting structural remodeling of the skin with accumulation of protein fibrous structures [3].

It has been shown that collagen-based preparations reduce β-galactosidase expression, increasing the expression of collagen precursors, p53, and p16 in skin cells [27]. Studies have demonstrated that the use of collagen-based preparations improves overall skin condition and slows aging by reducing wrinkle depth, enhancing hydration, decreasing transepidermal water loss, and normalizing skin density and elasticity [28, 29, 41].

Micronized native collagen powder requires hydration with saline solution; it is also possible to reconstitute the preparation with sterile and authorized hyaluronic acid and amino acid preparations [7, 22]. It should be noted that storage of the reconstituted collagen preparation for more than 2–3 hours is not permitted [7]. According to research, the most suitable solvent is saline solution, as it has osmolarity corresponding to blood plasma, significantly reducing pain during injection and the risk of osmotic shock to cells in the injection area [7].

A Russian study comparing the efficacy of biorevitalizers based on exogenous type I bovine collagen and hyaluronic acid in 60 patients (mean age 48 ± 7.6 years) demonstrated high efficacy for both methods: all groups achieved clinical improvement in the correction of age-related facial skin changes according to visual inspection, 3D photography, clinical scales, GAIS, and instrumental diagnostics. However, in the group receiving the collagen-based therapy, a significantly better effect was observed regarding skin elasticity [42].

A clinical case of using a type I collagen preparation derived from bovine skin in a 49-year-old patient with pronounced age-related changes (wrinkles around the eyes, forehead, glabella, nasolabial folds; reduced skin tone and turgor; facial contour changes) demonstrated improvement in facial tissue tone and turgor, restoration of facial contour, and activation of endogenous collagen synthesis with dermal structure restoration [43].

In a retrospective analysis of clinical data from 151 patients with dynamic facial wrinkles (including forehead, glabella, and periocular areas) and a Wrinkle Severity Rating Scale (WSRS) score ≥3, high clinical efficacy and WSRS improvement were observed in the group receiving intradermal injections of lyophilized type III collagen fibers over 30 days [44].

Evaluation of low-molecular-weight hyaluronic acid fragments combined with amino acids for facial rejuvenation in 20 women aged 35–64 years using intradermal injections demonstrated increased fibroblast activity. This led to production of reticular type III collagen, increased vascularization, and greater epidermal and dermal thickness [45]. A retrospective study of intradermal hyaluronic acid injections in 10 patients with infraorbital age-related skin changes showed clinically significant improvement in skin elasticity and firmness in the infraorbital area in 90% of cases [46].

Potential complications of injectable hyaluronic acid and micronized collagen preparations depend on the type of preparation and injection site. Non-ischemic complications may depend on injection technique and include local reactions, contour irregularities, inflammatory and infectious processes. In most cases, these adverse effects regress within 2–7 days [28, 30–32]. It should also be noted that treatment outcomes depend on appropriate selection of preparation concentrations according to the degree of decreased skin elasticity, including proper dilution and injection technique [7, 30, 31].

CONCLUSION

A course of intradermal injections of hyaluronic acid modified with amino acids and micronized collagen preparations can be recommended as a procedure for aesthetic correction of involutional skin changes and for the prevention of atrophic processes that significantly affect the appearance and health of the skin.

Currently, there are insufficient studies comparing the efficacy of these two groups of preparations; however, available results demonstrate the high potential of modified hyaluronic acid and micronized collagen preparations in correcting age-related skin changes. Further investigation and comparison of the efficacy and safety of modified hyaluronic acid preparations and micronized collagen preparations in injectable aesthetic medicine could substantially improve the quality of correction of involutional facial skin changes.

ADDITIONAL INFORMATION

Authors' contributions. E.S. Snarskaya ― concept and design, editing and making significant edits to the article in order to increase the scientific value of the literary review; A.I. Churbanova ― literature review, collection and analysis of literary sources, preparation and writing of the text of the article. Thereby, all authors provided approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding sources. No funding.

Disclosure of interests. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Statement of originality. When creating this work, fragments of his own text published earlier were used ([DOI: https://doi.org/10.17816/dv629582], distributed under the terms of the CC-BY 4.0 license).

Generative AI. Generative AI technologies were not used of this article creation.

Provenance and peer-review. This paper was submitted to the journal on an unsolicited basis and reviewed according to the usual procedure. Two external reviewers and the scientific editor of the publication participated in the review.

About the authors

Elena S. Snarskaya

Email: snarskaya-dok@mail.ru
ORCID iD: 0000-0002-7968-7663
SPIN-code: 3785-7859

MD, Dr. Sci. (Medicine), Professor

Anastasia I. Churbanova

Author for correspondence.
Email: spuzovskaya@mail.ru
ORCID iD: 0000-0001-8528-9197
SPIN-code: 2666-9461
Russian Federation, Moscow

References

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