Abstract
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 ECM- and 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.
References
Augello, F. R., Lombardi, F., Ciafarone, A., Ciummo, V., Altamura, S., Giuliani, M., Cinque, B., & Palumbo, P. (2024). Efficacy of an Innovative Poly-Component Formulation in Counteracting Human Dermal Fibroblast Aging by Influencing Oxidative and Inflammatory Pathways. Biomedicines, 12(9), 2030. https://doi.org/10.3390/biomedicines12092030.
Bar, O., & Valiukevičienė, S. (2025). Skin Aging and Type I Collagen: A Systematic Review of Interventions with Potential Collagen-Related Effects. Cosmetics, 12(4), 129. https://doi.org/10.3390/cosmetics12040129
Borg, M., Brincat, S., Camilleri, G., Schembri-Wismayer, P., Brincat, M., & Calleja-Agius, J. (2013). The role of cytokines in skin aging. Climacteric: The Journal of the International Menopause Society, 16(5), 514–521. https://doi.org/10.3109/13697137.2013.802303
Byun, K. A., Park, H. J., Oh, S., Son, K. H., & Byun, K. (2025). Polynucleotides Enhance Collagen Synthesis via Modulating Phosphoenolpyruvate Carboxykinase 1 in Senescent Macrophages: Experimental Evidence. International Journal of Molecular Sciences, 26(17), 8720. https://doi.org/10.3390/ijms26178720
Charoenchon, N., Rhodes, L. E., Nicolaou, A., Williamson, G., Watson, R. E. B., & Farrar, M. D. (2022). Ultraviolet radiation-induced degradation of dermal extracellular matrix and protection by green tea catechins: a randomized controlled trial. Clinical and Experimental Dermatology, 47(7), 1314–1323. https://doi.org/10.1111/ced.15179
Colaço, A. R. A., Furtado, P. S., Vanzan, D. F., da Silva, N. S., do Carmo, F. A., Cabral, L. M., Simon, A., Esteves, J. C., & Sathler, P. C. (2025). In Vivo Biostimulatory Efficacy of Ascorbic Acid-Loaded Poly (lactic-co-glycolic Acid) Nanoparticles Hydrogel for Dermal Remodeling. ACS Omega, 10(37), 42300–42312. https://doi.org/10.1021/acsomega.5c01910
Csekes, E., & Račková, L. (2021). Skin Aging, Cellular Senescence and Natural Polyphenols. International Journal of Molecular Sciences, 22(23), 12641. https://doi.org/10.3390/ijms222312641
Feng, C., Chen, X., Yin, X., Jiang, Y., & Zhao, C. (2024). Matrix Metalloproteinases on Skin Photoaging. Journal of Cosmetic Dermatology, 23(12), 3847–3862. https://doi.org/10.1111/jocd.16558
Lee, H., Hong, Y., & Kim, M. (2021). Structural and Functional Changes and Possible Molecular Mechanisms in Aged Skin. International Journal of Molecular Sciences, 22(22), 12489. https://doi.org/10.3390/ijms222212489
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023). Inflammation and aging: signaling pathways and intervention therapies. Signal Transduction and Targeted Therapy, 8(1), 239. https://doi.org/10.1038/s41392-023-01502-8
Liu, X., Li, X., & Ma, J. (2024). Beverage consumption and facial skin aging: Evidence from Mendelian randomization analysis. Journal of Cosmetic Dermatology, 23(5), 1800–1807. https://doi.org/10.1111/jocd.16153
Martic, I., Jansen-Dürr, P., & Cavinato, M. (2022). Effects of Air Pollution on Cellular Senescence and Skin Aging. Cells, 11(14), 2220. https://doi.org/10.3390/cells11142220
Mekić, S., Jacobs, L. C., Hamer, M. A., Ikram, M. A., Schoufour, J. D., Gunn, D. A., Kiefte-de Jong, J. C., & Nijsten, T. (2019). A healthy diet in women is associated with less facial wrinkles in a large Dutch population-based cohort. Journal of the American Academy of Dermatology, 80(5), 1358–1363. https://doi.org/10.1016/j.jaad.2018.03.033
Nan, L., Guo, P., Hui, W., Xia, F., & Yi, C. (2025). Recent advances in dermal fibroblast senescence and skin aging: unraveling mechanisms and pioneering therapeutic strategies. Frontiers in Pharmacology, (16), 1592596. https://doi.org/10.3389/fphar.2025.1592596
Pickart, L., & Margolina, A. (2018). Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data. International Journal of Molecular Sciences, 19(7), 1987. https://doi.org/10.3390/ijms19071987
Rodríguez-Castro, M. J., & Cortés-Rodríguez, A. E. (2025). Efficacy of platelet-rich plasma in facial rejuvenation: A systematic review. Enfermeria Clinica, 35(5), 502161. https://doi.org/10.1016/j.enfcle.2025.502161
Rovero, P., Malgapo, D. M. H., Sparavigna, A., Beilin, G., Wong, V., & Lao, M. P. (2022). The Clinical Evidence-Based Paradigm of Topical Anti-Aging Skincare Formulations Enriched with Bio-Active Peptide SA1-III (KP1) as Collagen Modulator: From Bench to Bedside. Clinical, Cosmetic and Investigational Dermatology, (15), 2693–2703. https://doi.org/10.2147/CCID.S374295
Salamito, M., Haydont, V., Pageon, H., Ruggiero, F., & Girardeau-Hubert, S. (2025). Collagen diversity in human skin: Aging, wound healing, and disorders. Matrix Biology, (140), 133–153. https://doi.org/10.1016/j.matbio.2025.07.006
Smythe, P., & Wilkinson, H. N. (2023). The Skin Microbiome: Current Landscape and Future Opportunities. International journal of molecular sciences, 24(4), 3950. https://doi.org/10.3390/ijms24043950
Sollitto, C. F., Narduzzi, M., & Wolinsky, C. (2025). A Systematic Review of Platelet-Rich Plasma Versus Platelet-Rich Fibrin for Periorbital Rejuvenation. Journal of Cosmetic Dermatology, 24(11), e70524. https://doi.org/10.1111/jocd.70524
Stellavato, A., La Noce, M., Corsuto, L., Pirozzi, A. V. A., De Rosa, M., Papaccio, G., Schiraldi, C., & Tirino, V. (2017). Hybrid Complexes of High and Low Molecular Weight Hyaluronans Highly Enhance HASCs Differentiation: Implication for Facial Bioremodelling. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 44(3), 1078–1092. https://doi.org/10.1159/000485414
Tan, M. G., Jo, C. E., Chapas, A., Khetarpal, S., & Dover, J. S. (2021). Radiofrequency Microneedling: A Comprehensive and Critical Review. Dermatologic Surgery, 47(6), 755–761. https://doi.org/10.1097/DSS.0000000000002972
Tao, B. K., Butt, F. R., Dhivagaran, T., Balas, M., Nijhawan, N., Nassrallah, G., Hussain, A., & Ing, E. B. (2025). Periocular Aging Across Populations and Esthetic Considerations: A Narrative Review. Journal of Clinical Medicine, 14(2), 535. https://doi.org/10.3390/jcm14020535
Tseng, C. H., & Wu, C. Y. (2025). From dysbiosis to longevity: a narrative review into the gut microbiome's impact on aging. Journal of Biomedical Science, 32(1), 93. https://doi.org/10.1186/s12929-025-01179-x
Wu, H. H., Chen, M. Q., Liu, J. H., Song, L. L., Luo, D. Q., Lu, J. F., & Zhao, Y. K. (2024). Combination of fractional carbon dioxide laser with recombinant human collagen in periocular skin rejuvenation. Journal of Cosmetic Dermatology, 23(1), 124–133. https://doi.org/10.1111/jocd.15942
Zhang, M., Lin, Y., Han, Z., Huang, X., Zhou, S., Wang, S., Zhou, Y., Han, X., & Chen, H. (2024). Exploring mechanisms of skin aging: Insights for clinical treatment. Frontiers in Immunology, (15), 1421858. https://doi.org/10.3389/fimmu.2024.1421858

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