Hybrid one session treatment with poly-l-lactic acid and high-molecular weight hyaluronic acid for skin rejuvenation: Clinical, ultrasound and histological assessment

Introduction. Poly-L-lactic acid (PLLA) has a multifactorial effect on skin aging. It stimulates extracellular matrix components synthesis. High-molecular weight hyaluronic acid (HA) offers the advantage of maintaining optimal skin hydration and inhibiting matrix metalloproteinases. The combination of these agents appears to be promising, as evidenced by the synergistic effect observed in their actions.

Aim. To evaluate the efficacy and safety of a hybrid one session treatment with PLLA and high-molecular weight HA for skin rejuvenation using both ultrasound (US) and histological diagnosis.

Materials and methods. Reconstituted PLLA was injected to a depth of 3–4 mm into the anterior abdominal wall in six healthy females. Intradermal injections of HA were conducted to a depth of 2–3 mm. The efficacy of the injection treatments was assessed after 24 hours and 6 weeks based on visual assessment, photography, US, and histologic examination.

Results. Six weeks after the treatment, the clinical signs included skin thickening and visual smoothing of the skin relief. Ultrasound results demonstrated zones of varying acoustic density, indicative of a gradual increase in connective tissue density. Areas of hyperechogenic density indicated structural reorganization and an increase in the number of connective tissue components. Histological examination of biopsy specimens confirmed active connective tissue restructuring. A comparison with the pre-treatment histology confirmed the formation of a denser network of collagen fibers at the level of dermis and subcutaneous adipose tissue.

Conclusions. The developed hybrid protocol was characterized by a favorable clinical efficacy and safety profile. These results were confirmed by histology and US, and were characterized by structural reorganization of connective tissue, with an accumulation of collagen fibers in the dermis and subcutaneous fat.

1. Kobayashi T, Chanmee T, Itano N. Hyaluronan: Metabolism and Function. Biomolecules. 2020;10(11):1525. https://doi.org/10.3390/biom10111525.

2. Wang F, Garza LA, Kang S, Varani J, Orringer JS, Fisher GJ, Voorhees JJ. In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin. Arch Dermatol. 2007;143(2):155–163. https://doi.org/10.1001/archderm.143.2.155.

3. Chen F, Guo X, Wu Y. Skin antiaging effects of a multiple mechanisms hyaluronan complex. Skin Res Technol. 2023;29(6):e13350. https://doi.org/10.1111/srt.13350.

4. Qin Z, Fisher GJ, Voorhees JJ, Quan T. Actin cytoskeleton assembly regulates collagen production via TGF‐β type II receptor in human skin fibroblasts. J Cell Mol Med. 2018;22(9):4085–4096. https://doi.org/10.1111/jcmm.13685.

5. Varì S, Minoretti P, Emanuele E. Human dermal fibroblast response to hyaluronic acid-based injectable dermal fillers: an in vitro study. Adv Dermatol Allergol. 2022;39(6):1088–1092. https://doi.org/10.5114/ada.2022.114927.

6. Glavnova AM, Kalashnikova NG, Kapuler OM, Murakov SV, Razumovskaya EA, Terent’eva LV, Timofeev AV. Consensus recommendations on the use of biorevitalization in mono- and combination protocols of aesthetic treatment. Klinicheskaya Dermatologiya i Venerologiya. 2024;23(5):601–610. (In Russ.) https://doi.org/10.17116/klinderma202423051601.

7. Oh S, Seo SB, Kim G, Batsukh S, Son KH, Byun K. Poly-D,L-Lactic Acid Stimulates Angiogenesis and Collagen Synthesis in Aged Animal Skin. Int J Mol Sci. 2023;24(9):7986. https://doi.org/10.3390/ijms24097986.

8. Ao YJ, Yi Y, Wu GH. Application of PLLA (Poly-L-Lactic acid) for rejuvenation and reproduction of facial cutaneous tissue in aesthetics: A review. Medicine. 2024;103(11):e37506. https://doi.org/10.1097/MD.0000000000037506.

9. Dong Y, Zhang Y, Yu H, Zhou L, Zhang Y, Wang H et al. Poly-l-lactic acid microspheres delay aging of epidermal stem cells in rat skin. Front Immunol. 2024;15:1394530. https://doi.org/10.3389/fimmu.2024.1394530.

10. Oh S, Lee JH, Kim HM, Batsukh S, Sung MJ, Lim TH, Lee MH, Son KH, Byun K. Poly-L-Lactic Acid Fillers Improved Dermal Collagen Synthesis by Modulating M2 Macrophage Polarization in Aged Animal Skin. Cells. 2023;12(9):1320. https://doi.org/10.3390/cells12091320.

11. Chuang FJ, Wang YW, Chang LR, Chang CY, Cheng HY, Kuo SM. Enhanced skin neocollagenesis through the transdermal delivery of poly-L-lactic acid microparticles by using a needle-free supersonic atomizer. Biomater Adv. 2023;154:213619. https://doi.org/10.1016/j.bioadv.2023.213619.

12. Byun KA, Lee JH, Lee SY, Oh S, Batsukh S, Cheon G woo, Lee D et al. Piezo1 Activation Drives Enhanced Collagen Synthesis in Aged Animal Skin Induced by Poly L-Lactic Acid Fillers. Int J Mol Sci. 2024;25(13):7232. https://doi.org/10.3390/ijms25137232.

13. Razumovskaya EA, Kapuler OM, Murakov SV, Glavnova AM. The use of polyL-lactic acid in case of involutional changes in the body skin: clinical, ultrasound and histological assessment of effectiveness. Plastic Surgery and Aesthetic Medicine. 2024;(3):62–70. (In Russ.) https://doi.org/10.17116/plast.hirurgia202403162.

14. Kalashnikova NG, Murakov SV. Clinical Evaluation of the Effectiveness of Combined Neocollagenogenesis Stimulation with High-Intensity Focused Ultrasound (HIFU) and Poly-L-Lactic Acid (PLLA) in Involutional Skin Changes. Klinicheskaya Dermatologiya i Venerologiya. 2024;23(6):691–702. (In Russ.) https://doi.org/10.17116/klinderma202423061691.

15. Urdiales‐Gálvez F, De cabo‐Francés FM, Bové I. Ultrasound patterns of different dermal filler materials used in aesthetics. J Cosmet Dermatol. 2021;20(5):1541-1548. https://doi.org/10.1111/jocd.14032.

16. Czajkowska J, Juszczyk J, Bugdol MN, Glenc-Ambroży M, Polak A, Piejko L, Pietka E. High-frequency ultrasound in anti-aging skin therapy monitoring. Sci Rep. 2023;13:17799. https://doi.org/10.1038/s41598-023-45126-y.

17. Tobin DJ. Introduction to skin aging. J Tissue Viability. 2017;26(1):37–46. https://doi.org/10.1016/j.jtv.2016.03.002.

18. de Melo F, Carrijo A, Hong K, Trumbic B, Vercesi F, Waldorf HA, Zenker S. Minimally Invasive Aesthetic Treatment of the Face and Neck Using Combinations of a PCL-Based Collagen Stimulator, PLLA/PLGA Suspension Sutures, and Cross-Linked Hyaluronic Acid. Clin Cosmet Investig Dermatol. 2020;13:333–344. https://doi.org/10.2147/CCID.S248280.

19. Tam E, Choo JPS, Rao P, Webb WR, Carruthers JDA, Rahman E. A Systematic Review on the Effectiveness and Safety of Combining Biostimulators with Botulinum Toxin, Dermal Fillers, and Energy-Based Devices. Aesthetic Plast Surg. 2024. https://doi.org/10.1007/s00266-024-04627-5.

20. Oh H, Lee S, Na J, Kim JH. Comparative Evaluation of Safety and Efficacy of a Novel Hyaluronic Acid-polynucleotide/Poly-L-lactic Acid Composite Dermal Filler. Aesthetic Plast Surg. 2021;45(4):1792–1801. https://doi.org/10.1007/s00266-021-02295-3.

21. Su D, Yang W, He T, Wu J, Zou M, Liu X et al. Clinical applications of a novel poly-L-lactic acid microsphere and hyaluronic acid suspension for facial depression filling and rejuvenation. J Cosmet Dermatol. 2024;23(11):3508–3516. https://doi.org/10.1111/jocd.16446.

22. Kollipara R, Hoss E, Boen M, Alhaddad M, Fabi SG. A Randomized, Split-Body, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Poly-L-lactic Acid for the Treatment of Upper Knee Skin Laxity. Dermatol Surg. 2020;46(12):1623–1627. https://doi.org/10.1097/DSS.0000000000002685.

23. Mazzuco R, Dal’Forno T, Hexsel D. Poly-L-Lactic Acid for Nonfacial Skin Laxity. Dermatol Surg. 2020;46(Suppl. 1):S86–S88. https://doi.org/10.1097/DSS.0000000000002390.

24. Fakih-Gomez N, Kadouch J. Combining Calcium Hydroxylapatite and Hyaluronic Acid Fillers for Aesthetic Indications: Efficacy of an Innovative Hybrid Filler. Aesthetic Plast Surg. 2022;46(1):373–381. https://doi.org/10.1007/s00266-021-02479-x.