Regenerative Dermatology in Ukraine: Clinical, Microbiological, and Biochemical Markers of the Effectiveness of Modern Protocols for the Treatment of Involutive Skin Changes

2025 Vol. 2 No. 2 https://www.eujini.org.pl 98 ISSN 3071-9658 https://www.eujini.org.pl Regenerative Dermatology in Ukraine: Clinical, Microbiological, and Biochemical Markers of the Effectiveness of Modern Protocols for the Treatment of Involutive Skin Changes Olena Arutiunova 1 * 1 Arutiunova Skin Health Clinic, Ivano-Frankivsk (Ukraine). Dermatologist. * Corresponding Author, e-mail: [email protected] ARTICLE INFO ABSTRACT Research Article Received: 10 May 2025 Revised: 18 June 2025 Accepted: 01 July 2025 Published online: 15 July 2025 Copyright © 2025 by author This is an open access journal and all published articles are licensed under a Creative Commons Attribution— NonCommercial 4.0 International (CC BY-NC 4.0) DOI: 10.5281/ zenodo.18018674 Involutional skin changes are the result of complex disturbances in extracellular matrix homeostasis, cellular senescence, cytokine imbalance, and microbiome disorganization, which has led to growing interest in regenerative technologies in dermatology. The study aims to systematize modern regenerative treatment protocols for involutive skin changes and to summarize the clinical, microbiological, and biochemical indicators of their effectiveness. It also aims to develop an author’s approach to the treatment of involutive skin changes, taking into account the possibilities of its implementation in Ukrainian clinical practice. An analytical review of current publications selected from international databases was conducted, focusing on randomized clinical trials and molecular biology studies that evaluated changes in dermal parameters under the influence of various regenerative interventions. The article showed that plasmatherapy ensures rapid normalization of coagulation homeostasis by increasing the synthesis of collagen types I and III and reducing the activity of matrix metalloproteinases. It has also been established that polynucleotides have a pronounced antioxidant and cytokine-modulating effect and contribute to a stable increase in dermis thickness. Meanwhile, peptide complexes demonstrate a restructuring effect on the matrix with inhibition of matrix metalloproteinase-1 and stimulation of neocollagenesis. Hyaluronic acid preparations (especially in combination with amino acids) improve skin hydration and mechanical properties, while hardware techniques (microneedle RF lifting, fractional lasers) provide deep controlled remodeling of the dermis. The highest clinical and morphological efficacy has been demonstrated with combined protocols that simultaneously affect the structural, inflammatory, and oxidative links in the pathogenesis of aging. The authors presented their approaches to the treatment of involutive skin changes. These are “Deep Biostimulation of the Dermis”, which is aimed at correcting the loss of density associated with the degradation of collagen fibers, and “Matrix Boost” for working with pronounced involutive changes. Regenerative techniques play a leading role in the treatment of involutive skin changes, and their use should be based on an understanding of ECMand cytokine-dependent mechanisms of action. The conclusions justify the standardization of combined treatment protocols for involutive skin changes and the development of national clinical guidelines in the field of regenerative dermatology in Ukraine. KEYWORDS regenerative dermatology, involutive skin changes, extracellular matrix, plasma therapy, combined treatment protocols Olena Arutiunova , 2(2) https://www.eujini.org.pl 99 Introduction ontemporary regenerative dermatology represents an integrative approach to managing involutive skin changes, combining clinical assessments, microbiological profiles, and biochemical markers to monitor and predict therapeutic efficacy. Within the context of the Ukrainian medical system, there is a growing need for harmonized protocols that account for local epidemiological characteristics, resource availability, and regulatory requirements. The skin, comprising the epidermis (outer layer), the thicker and more elastic dermis (middle layer), and the subcutaneous tissue (inner layer), serves as the body’s largest organ facilitating interaction with the environment. Research has established that the skin aging process results from the combined impact of both intrinsic and extrinsic factors. These include solar radiation exposure, air pollution, tobacco use, nutritional deficiencies, and the improper use of cosmetics (Martic et al., 2022; Tao et al., 2025). A healthy diet, including adequate hydration, antioxidants (e.g., vitamins A, C, and E), and carotenoids, is associated with reduced facial wrinkling. Other potential risk factors include chronic stress, the persistence of dynamic wrinkles caused by repetitive facial expressions (e.g., squinting) or sleep distortions, and generally poor sleep hygiene (Mekić et al., 2019; Liu et al., 2024). Furthermore, skin aging is closely linked to the dysregulation of the accumulation and degradation of extracellular matrix (ECM) components, which provide structural and functional support to skin tissues (Charoenchon et al., 2022). Researchers define ECM degradation as an indicator of the breakdown of collagen and elastin fibers. In the healthy skin of young individuals, collagen synthesis occurs continuously, while damaged or excessive collagen undergoes degradation. However, the aging process involves a decline in collagen synthesis capacity, leading to a gradual loss of collagen content (Rovero et al., 2022; Bar & Valiukevičienė, 2025). This underscores the importance of maintaining balanced ECM turnover to retard skin aging. Consequently, involutive skin changes are the result of complex disruptions in ECM homeostasis, cellular senescence, cytokine imbalance, and microbiome disorganization. Precisely these changes drive the growing interest in regenerative technologies in dermatology and indicate the necessity for further development in this field. Literature Review urrently, involutive skin changes are viewed as a multifactorial biological process encompassing a range of interconnected structural, cellular, and biochemical disruptions that accumulate gradually under the influence of chronological aging, photoaging, and external aggressive factors. According to Charoenchon et al. (2022) and Feng et al. (2024), age-related changes are accompanied by a decrease in the synthesis of Type I and Type III collagen, disrupted ECM organization, reduced mechanical stability of the dermis, and increased activity of matrix metalloproteinases (MMPs)—primarily MMP-1 and MMP-3—which initiates intensive degradation of collagen structures. It has been proven that cellular senescence plays a leading role in shaping the phenotype of aged skin. Senescent fibroblasts produce elevated levels of IL-6, IL-1β, and TNF-α, forming a senescenceassociated secretory phenotype (SASP). This phenotype sustains chronic low-grade inflammation and stimulates ECM degradation via MMP activation (Li et al., 2023). Ultraviolet radiation, environmental pollution, and oxidative stress significantly accelerate these processes. Studies by Bar & Valiukevičienė (2025), Martic et al. (2022), and Colaço et al. (2025) have established that UV exposure leads to elevated MMP-1 levels, fibroblast DNA damage, disruption of elastin structure, and deepening dermal atrophy. Researchers Feng et al. (2024), Smythe & Wilkinson (2023), and Tseng & Wu (2025) note that a critical pathogenetic characteristic of involutive changes is the alteration of the skin microbiome. According to Park et al., the age-related decline in microbiome diversity, a decrease in the proportion of Staphylococcus epidermidis, and a relative increase in Cutibacterium acnes are associated with chronic inflammation, impaired barrier function, and accelerated degradation of dermal components. Thus, skin aging is the consequence of a cumulative imbalance of the ECM, cellular dysfunction, and microbiological shifts. C C Olena Arutiunova , 2(2) https://www.eujini.org.pl 100 The absence of standardized protocols and a unified clinical-diagnostic approach creates substantial difficulties in implementing regenerative technologies into broad dermatological practice in Ukraine. The optimization of combined protocols (injectable and device-based) is also a pressing issue, as research data suggest a synergistic effect when simultaneously targeting different links in the pathogenesis of aging (Wu et al., 2024; Rodríguez-Castro & Cortés-Rodríguez, 2025). The development of regenerative dermatology in recent years has opened the possibility of targeted intervention in these pathogenetic mechanisms. However, despite a significant evidence base in global literature, Ukraine still lacks unified clinical protocols for the application of platelet-rich plasma/fibrin (PRP/PRF), polynucleotides, peptide complexes, amino acid biostimulators, hyaluronic acid preparations, and energy-based device technologies. There is also a lack of systematized data regarding optimal combinations of these methods for patients with different aging phenotypes. In most existing Ukrainian clinical practices, the evaluation of molecular and biochemical markers of therapeutic response is not conducted, whereas contemporary international studies prove that MMP1/MMP-3, TIMP-1, COL1A1/COL3A1, cytokine profiles, and microbiome status are the most accurate objective criteria for the efficacy of regenerative interventions. Thus, the problem lies in the absence of systematized, evidence-based approaches to treating involutive skin changes in Ukraine, a shortage of standardized clinical protocols, and the lack of consistent application of objective efficacy markers. This necessitates a comprehensive analytical study of modern regenerative technologies, their impact on biochemical, morphological, and microbiome parameters, and the formation of a scientifically grounded basis for standardizing protocols in Ukrainian dermatological practice. Problem Statement his study aims to systematize modern regenerative protocols for the treatment of involutive skin changes and to generalize the clinical, microbiological, and biochemical indicators of their efficacy. Furthermore, the study aims to develop a proprietary approach to treating involutive skin changes, considering the feasibility of implementation into Ukrainian clinical practice. The objectives of the research included analyzing contemporary concepts of skin involution processes, evaluating the impact of regenerative methodologies on microbiological and biochemical markers, formulating scientifically grounded recommendations for implementing effective regenerative protocols in Ukrainian dermatological practice, and developing proprietary protocols. Methods and Materials n analytical review of contemporary publications selected from international databases was conducted, focusing on randomized clinical trials and molecular-biological studies evaluating changes in dermal parameters under the influence of various regenerative interventions. The study utilized methods of analysis, synthesis, and data generalization. Additionally, proprietary protocols for the treatment of involutive skin changes were developed. Results and Discussion n modern dermatological science, involutive skin changes are regarded as a multicomponent process involving structural, biochemical, and immune disruptions that accumulate with age and are significantly accelerated by external factors. Chronological skin aging is accompanied by a substantial decline in Type I and Type III collagen synthesis, reduced dermal density, and increased activity of matrix metalloproteinases, primarily MMP-1 and MMP-3, which has been quantitatively confirmed by histochemical and immunological methods. Authors Tan et al. (2021) and Feng et al. (2024) note that the imbalance between the synthesis and degradation of structural ECM proteins is the key link in the formation of morphological signs of aging. The pathogenetic role of cellular senescence has also been proven by a series of contemporary studies. Zhang et al. (2024) and Nan et al. (2025) demonstrated that senescent dermal fibroblasts produce elevated concentrations of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α, forming the SASP phenotype, which sustains chronic low-grade inflammation. An increase in the number of senescent cells correlates directly with reduced elasticity and deteriorated skin texture. T A I Olena Arutiunova , 2(2) https://www.eujini.org.pl 101 The impact of ultraviolet radiation on the formation of involutive skin changes is confirmed in the work of Bar & Valiukevičienė (2025), which established that chronic UV exposure leads to significantly elevated MMP-1 activity, reduced collagen expression, and disruption of elastin fibers. The authors emphasize that photoaging has a more pronounced destructive effect on the ECM compared to chronological aging, attributed to the intensive formation of reactive oxygen species (ROS) and the activation of inflammatory cascades. Significant attention from the scientific community is also paid to changes in the skin microbiome during aging. Studies by Smythe & Wilkinson (2023) and Tseng & Wu (2025) proved that age-related reduction in microbiome diversity and imbalance of commensal bacteria—primarily a decrease in Staphylococcus epidermidis frequency and a relative increase in Cutibacterium acnes—are accompanied by increased local inflammatory activity and accelerated degradation of structural components in the dermis. Microbiome dysfunction is not merely a consequence but a catalyst for pathological skin changes, as barrier function impairment creates conditions for persistent inflammation. Biochemical markers of skin aging are actively studied in research by Borg et al. (2013), Lee et al. (2021), and Salamito et al. (2025). The authors established that aging is accompanied by decreased expression of COL1A1 and COL3A1, reduced TIMP-1 levels, and increased MMP-1/3 activity, confirmed by biopsy data and genetic expression analysis. Such biomarkers can serve as objective indicators of the efficacy of regenerative interventions. Substantial interest in modern science is drawn to the impact of regenerative methods, particularly PRP, on cellular and biochemical skin homeostasis. Rodríguez-Castro & Cortés-Rodríguez (2025) showed that PRP application leads to increased expression of collagen genes COL1A1 and COL3A1, reduced MMP-1 activity, and normalization of pro-inflammatory cytokine levels. Clinically, this manifests as improved elasticity, reduced wrinkle depth, and improved skin relief. Sollitto et al. (2025) proved that PRF possesses a similar mechanism of action with a more prolonged cellular effect due to the slow release of growth factors. Their study demonstrated that PRF provides a significant increase in skin density, improves morphometric parameters, and reduces subclinical inflammation, confirmed by altered levels of IL-6 and TNF-α. Researchers have proven that the state of the extracellular matrix, MMP activity, cytokine levels, cellular senescence indicators, and skin microbiome balance are the defining parameters reflecting the degree of involutive changes and simultaneously characterizing the skin’s response to PRP/PRF, polynucleotides, and other technologies. Given the high level of evidence for these markers, their use as reference indicators in the comparative analysis of various regenerative interventions is deemed appropriate (Table 1). Analysis of the data in Table 1 demonstrates that involutive skin changes form against a background of systemic ECM homeostasis disruption, increased MMP-1 and MMP-3 activity, reduced inhibitory potential of TIMP-1, and decreased expression of collagen genes, which aligns with the morphological manifestations of age-related remodeling. The presented studies demonstrate that PRP/PRF, polynucleotides, peptide complexes, and HAdermostimulators exert a multicomponent influence on key pathogenetic links of aging. This ensures a reduction in metalloproteinase activity, normalization of pro-inflammatory cytokines, and increased COL1A1 expression. Furthermore, morphometric studies confirm an increase in dermal thickness and improved skin elastic properties following a course of regenerative interventions, indicating their ability to restore dermal structural integrity at cellular and tissue levels. The key structural component defining the morphological state of the skin is the ECM, consisting of collagen, elastin, glycosaminoglycans, proteoglycans, and other structural molecules that provide mechanical stability and biological activity to the dermis. Csekes & Račková (2021) showed that aging involves a decrease in procollagen-1 synthesis, disrupted organization of collagen fibers, and increased fragmentation under the influence of MMP-1 and MMP-3, confirmed by molecular immunohistochemical tests. It is ECM dysfunction that constitutes the primary link in involutive changes, facilitating subsequent fibroblast senescence. Olena Arutiunova , 2(2) https://www.eujini.org.pl 102 Table 1. Key Biochemical, Microbiological, and Morphological Markers of Involutive Skin Changes and the Impact of Regenerative Methodologies Marker Group Specific Marker Changes in Involutive Aging Proven Effect of Regenerative Methods Sources ECM Markers MMP-1 Increased activity; degradation of Collagen I Activity reduction by 20–35% after PRP/PRF, PN, RF-needling Feng et al., 2024; Byun et al., 2025 MMP-3 Proteoglycan destruction; intensification of dermal atrophy Partial normalization after PN, peptides, and laser methods Augello et al., 2024 TIMP-1 Decreased MMP inhibition; ECM imbalance Increase in TIMP-1 after PRP/PRF and PN Borg et al., 2013 COL1A1 Expression decreases by 25–40% Expression increases by 25–40% after PRP/PRF, PN, HA Rodríguez-Castro & Cortés-Rodríguez (2025) COL3A1 Decreased synthesis of fibers in the dermis Significant increase after combined protocols Sollitto et al. (2025) Inflammatory Markers IL-6 Elevation (SASP, chronic inflammation) Reduction after PRP/PRF, PN; normalization after laser Nan et al. (2025) TNF-α Elevation; MMP stimulation Reduction in response to PRF and PN Salamito et al., 2025 IL-1β Activation of SASP Modulation via PRP/PRF Zhang et al. (2024), Nan et al. (2025) Senescence Marker p16INK4a Increase; accumulation of senescent cells Partial reduction after PRP and PN Zhang et al. (2024), Nan et al. (2025) Microbiome Markers Staphylococcus epidermidis Decrease; reduced barrier function Normalization after regenerative interventions Smythe & Wilkinson (2023), Tseng & Wu (2025) Cutibacterium acnes Relative increase; intensification of inflammation Reduction after PRP/PRF and laser therapy Smythe & Wilkinson (2023), Tseng & Wu (2025) Morphological Indicators Dermal Thickness (Morphometry) Decrease by 15–30% Increase by 18–32% after RFneedling, PN, PRP/PRF Tan et al., 2021 Skin Elasticity (Cutometer) Decrease in R2, R5 Improvement by 12–28% after PRP/HA/PN Lee et al., 2021 Hydration (Corneometer) Disruption of hydrobalance Significant increase after HA injections and amino acid stimulators Stellavato et al., 2017 Notes: PN – Polynucleotides; PRP – Platelet-Rich Plasma; HA – Hyaluronic Acid. Comparison of the efficacy of different classes of injectable techniques—PRP/PRF, polynucleotides, peptide complexes, and hyaluronic dermostimulators—is of significant value in regenerative dermatology. Byun et al. (2025) and Sollitto et al. (2025) established that PRP and PRF provide the most intensive stimulation of fibroblasts due to high concentrations of growth factors (PDGF, VEGF, TGF-β). The authors showed that PRP increases COL1A1 and COL3A1 expression by 34% and 29% respectively, while PRF demonstrates a more prolonged effect due to the gradual release of growth factors. In-depth analysis of ECM degradation mechanisms indicates that the balance between MMPs and their inhibitors (TIMPs) is a critical regulator. According to Augello et al. (2024), a 30–45% decrease in TIMP-1 in aged skin leads to uncontrolled proteolysis of structural proteins, whereas TIMP-1 restoration following regenerative interventions (PRP, polynucleotides, peptides) associates with improved morphometric indicators and increased dermal mechanical resistance. Scientific studies by Salamito et al. (2025) confirmed that COL1A1 and COL3A1 levels increase by 25–40% in patients after PRP therapy, aligning with reduced MMP-1/3 activity based on biochemical analysis. According to results by Augello et al. (2024), polynucleotides exert a more pronounced effect on reducing oxidative stress markers (ROS reduction by 18–25%) and stimulating A2A receptors, mediating neocollagenesis activation. Polynucleotides are shown to provide a gradual increase in dermal thickness by 15–22% within 2–3 months of therapy. Conversely, peptide complexes, particularly GHK-Cu and tri-/tetrapeptides, demonstrate a combined mechanism of action. They stimulate ECM protein synthesis, modulate inflammatory pathways, and restore angiogenesis. Olena Arutiunova , 2(2) https://www.eujini.org.pl 103 Research by Pickart & Margolina (2018) established that GHK-Cu increases procollagen-1 expression by 23–37% and lowers MMP-1 activity, confirming its regenerative potential. Hyaluronic acid preparations, according to Lee et al. (2021), ensure significant improvement in skin hydration and elasticity, but their biostimulating potential increases substantially when combined with amino acids, evidenced by a 30–35% increase in procollagen-1 after a course of procedures. A number of papers compare the efficacy of injectable methods directly. Rovero et al. (2022) showed that polynucleotides provide better MMP-1 normalization compared to hyaluronic acid, while PRF provides the greatest increase in dermal density based on ultrasound morphometry. Tan et al. (2021) established that RF-needling combined with PRP ensures a substantial increase in dermal thickness by 27% and a significant reduction in MMP-1 activity compared to monotherapy. In a randomized study, Wu et al. (2024) proved that fractional CO₂ laser combined with polynucleotides ensures the highest gain in collagen density and the highest GAIS scores among all studied groups. Regenerative methodologies have a pronounced impact on ECM homeostasis, fibroblast activity, the microbiome, and inflammatory processes, and their efficacy largely depends on specific mechanisms of action. The obtained data confirm the superiority of combined protocols that ensure multi-level regeneration and restoration of skin structural integrity, which serves as an important foundation for standardizing such regimens in Ukrainian dermatological practice. To enhance the efficacy of treating involutive skin changes, the author developed and tested protocols oriented not toward an “instant effect”, but toward long-term results and skin health restoration. These are the “Deep Dermal Biostimulation” and “Matrix Boost” protocols. The first is aimed at correcting density loss associated with collagen fiber degradation and includes: – Preliminary tissue preparation to improve vascularization; – Injection of highly concentrated plasma at various dermal levels according to ultrasound data; – Phased regeneration (activation – stimulation – restructuring). The “Matrix Boost” protocol was developed for addressing pronounced involutive changes: – PRP combined with extracellular matrix stimulators; – Specific injection technique for uniform distribution of bioactive factors; – Dynamic monitoring with correction of intervals between procedures. The data obtained and synthesized indicate that involutive skin changes are the consequence of multicomponent dysfunction, including ECM homeostasis disruption, altered fibroblast activity, cell senescence, elevated pro-inflammatory cytokine levels, and microbiome dysbiosis. The established patterns allow for the identification of key pathogenetic mechanisms that regenerative interventions must target. Studies by Zhang et al. (2024) and Nan et al. (2025) proved that the activation of metalloproteinases MMP-1 and MMP-3 is the primary driver of collagen and elastin structure degradation, while reduced TIMP-1 contributes to the progression of dermal atrophy. Concurrently, these data align with clinical observations by other authors such as Feng et al. (2024), who document reduced skin elasticity and turgor in older patient groups. The application of PRP/PRF methodologies demonstrates the most pronounced impact on early and mid-term markers of ECM regeneration. A series of studies, notably Rodríguez-Castro & CortésRodríguez (2025) and Salamito et al. (2025), showed that PRP/PRF usage leads to the restoration of the COL1A1/COL3A1 ratio, reduction of MMP-1 activity, and normalization of IL-6 and TNF-α levels. This indicates the capacity of PRP/PRF to influence both structural and inflammatory mechanisms of aging, providing a biomodulatory effect. Simultaneously, studies by Sollitto et al. (2025) demonstrate a prolonged effect of PRF, explained by the slower release of growth factors from the fibrin scaffold and better cellular integration. According to data by Byun et al. (2025) and Augello et al. (2024), polynucleotides demonstrate the most pronounced impact on the oxidative component of pathogenesis. They exert an antioxidant effect by activating A2A receptors, reducing ROS quantities, and normalizing the cytokine profile. These changes are accompanied by improved ECM homeostasis, reduced MMP activity, and improved morphometric indicators. Polynucleotides exhibit the most pronounced effect in the medium term (8–12 weeks), distinguishing them from PRP/PRF, which provide a faster but less sustained response. Olena Arutiunova , 2(2) https://www.eujini.org.pl 104 Peptide complexes demonstrated the ability to modulate fibroblast cellular activity, reduce MMP-1 activity, and stimulate neocollagenesis, confirmed by significant increases in dermal density in publications by Pickart & Margolina (2018) and Rovero et al. (2022). Comparative data suggest that peptides provide a milder but stable regenerative effect, particularly pronounced when used in combination with hyaluronic acid dermostimulators. Specifically, hyaluronic acid, according to works by Lee et al. (2021) and Stellavato et al. (2017), ensures not only improved hydration but also exhibits its own biostimulating effect, especially in low-molecular-weight forms. It is noted that they display maximum efficacy in patients with a thin aging phenotype, where hydration disorders and reduced turgor dominate. Device-based methodologies, particularly RF-needling and fractional CO₂ lasers, demonstrate significant advantages in cases of pronounced photoaging or the presence of coarse structural dermal changes. According to Tan et al. (2021), RF-needling ensures a 19–27% increase in dermal thickness and improves ECM architecture. Research by Wu et al. (2024) proved that CO₂ laser combined with polynucleotides ensures the highest level of ECM remodeling, the greatest reduction in MMP-1, and the best GAIS scores after a full course of procedures. Summarizing the research results, it can be stated that all regenerative methodologies exert a positive influence on involutive skin changes, yet the effects differ in mechanism of action, response duration, and intensity of structural changes. PRP/PRF demonstrate the fastest initial effect; polynucleotides, the most balanced medium-term impact; peptides, a stable restructuring effect; HA, a pronounced influence on hydration and elasticity; while device-based methods ensure the deepest ECM remodeling. It is crucial to emphasize that the most significant clinical changes are noted specifically with combined protocols, where injectable methods are paired with device technologies. Such an approach ensures a synergistic effect by targeting different links of pathogenesis, and the reduction of MMP activity, normalization of collagen architecture, reduction of pro-inflammatory cytokines, and microbiome restoration create conditions for sustained dermal repair. In the course of this work, proprietary approaches to treating involutive skin changes were developed: “Deep Dermal Biostimulation”, aimed at correcting density loss associated with collagen fiber degradation, and “Matrix Boost” for working with pronounced involutive changes. The results obtained confirm the necessity of standardizing combined protocols in Ukrainian dermatology and justify their inclusion in modern clinical guidelines. Conclusions nalysis of literature data indicates that involutive skin changes result from a complex interaction of structural, cellular, inflammatory, and microbiological mechanisms, among which the central place belongs to ECM homeostasis disruption, reduced fibroblast activity, increased metalloproteinase expression, and SASP phenotype formation. The presented results demonstrate that all analyzed regenerative therapy methods (PRP/PRF, polynucleotides, peptide complexes, hyaluronic biostimulators, and device technologies) exert a significant impact on key pathogenetic links of aging, facilitating the restoration of the skin's structural and functional integrity. The application of PRP and PRF ensures the most rapid ECM restoration through fibroblast stimulation, increased synthesis of Type I and III collagen, and reduced MMP-1/MMP-3 activity. Polynucleotides demonstrate a pronounced medium-term effect, reducing oxidative stress, normalizing the cytokine profile, and restoring dermal morphometric parameters. Peptide complexes ensure a stable restructuring influence on the ECM, especially in patients with combined manifestations of aging. Hyaluronic acid preparations and amino acid dermostimulators showed high efficacy in restoring hydro-balance, improving elasticity, and supporting basal dermal repair processes. Device-based methodologies, including RF-needling and fractional laser systems, demonstrated the capacity to induce controlled thermal remodeling, leading to deep and prolonged ECM restoration. The most pronounced results were achieved with the combined application of these technologies with injectable methodologies, confirming the expediency of a multifactorial impact on the pathogenesis of involutive changes. A Olena Arutiunova , 2(2) https://www.eujini.org.pl 105 Regenerative methodologies occupy a leading place in the treatment of involutive skin changes, and their application must be based on an understanding of ECMand cytokine-dependent mechanisms of action. Proprietary approaches to treating involutive skin changes were presented: “Deep Dermal Biostimulation”, directed at correcting density loss associated with collagen fiber degradation, and “Matrix Boost” for addressing pronounced involutive changes. The generalizations obtained justify the expediency of standardizing combined protocols for treating involutive skin changes and developing national clinical guidelines in the field of regenerative dermatology in Ukraine. Future research in the field of regenerative dermatology should be directed toward an in-depth study of the molecular mechanisms of extracellular matrix remodeling and the determination of optimal combinations of biostimulating and device-based methodologies in patients with different phenotypes of involutive skin changes. Special attention is required for the standardization of a panel of biochemical and microbiological markers that can serve as objective criteria for evaluating the regenerative response and allow for precise patient stratification. References Augello, F. R., Lombardi, F., Ciafarone, A., Ciummo, V., Altamura, S., Giuliani, M., Cinque, B., & Palumbo, P. (2024). 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