Aesthetic Plastic Surgery

, Volume 39, Issue 1, pp 129–133 | Cite as

Mesotherapy with an Intradermal Hyaluronic Acid Formulation for Skin Rejuvenation: An Intrapatient, Placebo-Controlled, Long-Term Trial Using High-Frequency Ultrasound

  • Aurora Tedeschi
  • Francesco Lacarrubba
  • Giuseppe Micali
Original Article Non-Surgical Aesthetic


Mesotherapy with hyaluronic acid (HA) is a treatment approach currently used for skin rejuvenation. High-frequency ultrasound (20–100 MHz) is a non-invasive technique that has been used to evaluate age-related dermal changes. The presence and the degree of a typical subepidermal low-echogenic band (SLEB) are photoaging related: the lower the SLEB echogenicity, the higher the photoaging. The aim of this trial was to evaluate, through ultrasound imaging, the long-term effects of microinjections of HA on SLEB echogenicity. Twenty-two women with clinical and ultrasound signs of moderate photoaging were enrolled in the study. Treatment consisted of multiple microinjections of HA salts of biotechnological origin on the dorsum of one hand, once weekly for 4 weeks and, successively, once monthly for 4 months (group A) or 9 months (group B). The dorsum of the other hand of each subject was injected with saline solution and used as a control. In all subjects, high-frequency ultrasound (22 MHz) was performed to evaluate SLEB echogenicity changes during treatment. Eighteen out of 22 patients completed the study. At the end of 4 weeks, an ultrasound increase of dermal echogenicity was observed in 13 subjects (seven of group A and six of group B), which we considered as “responders”. In these patients, the Student’s t-test showed a significant increase from baseline of SLEB pixel numbers of +24 % (P < 0.01) versus +6 % with placebo. In the same subjects, after an additional 4 months of monthly injections, the mean increase was +18 % (P < 0.05) versus +4 % with placebo. In patients from group B that completed 10 months of treatment, the increase from baseline of SLEB pixel numbers was +18 % (P < 0.05) versus 0 % with placebo. Our study suggests that mesotherapy with HA may effectively improve skin aging and photoaging, as supported by quantifiable ultrasound data showing significant changes in SLEB density over time.

Level of Evidence II

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors


Mesotherapy Hyaluronic acid Ultrasound Skin rejuvenation 



The authors wish to thank Dr. Guido Robecchi for his invaluable assistance.

Conflict of interest

The authors declare that they have no conflicts of interest to disclose.


  1. 1.
    Stern R, Maibach HI (2008) Hyaluronan in skin: aspects of aging and its pharmacologic modulation. Clin Dermatol 26:106–122PubMedCrossRefGoogle Scholar
  2. 2.
    Prehm P (1984) Hyaluronate is synthesized at plasma membranes. Biochem J 220:597–600PubMedCentralPubMedGoogle Scholar
  3. 3.
    Streker M, Reuther T, Krueger N, Kerscher M (2013) Stabilized hyaluronic acid-based gel of non-animal origin for skin rejuvenation: face, hand, and décolletage. J Drugs Dermatol 12(9):990–994PubMedGoogle Scholar
  4. 4.
    Kaya G, Saurat JH (2007) Dermatoporosis: a chronic cutaneous insufficiency/fragility syndrome. Clinicopathological features, mechanisms, prevention and potential treatments. Dermatology 215(4):284–294PubMedCrossRefGoogle Scholar
  5. 5.
    Atiyeh BS, Ibrahim AE, Dibo SA (2008) Cosmetic mesotherapy: between scientific evidence, science fiction, and lucrative business. Aesthetic Plast Surg 32:842–849PubMedCrossRefGoogle Scholar
  6. 6.
    Lacarrubba F, Nardone B, Tedeschi A, Nordstrom R, Micali G (2007) Ultrasound evaluation of mesotherapy for skin rejuvenation. In: Tosti A, De Padova MP (eds) Atlas of mesotherapy in skin rejuvenation. Informa Healthcare Ltd, LondonGoogle Scholar
  7. 7.
    Jemec GB, Gniadecka M, Ulrich J (2000) Ultrasound in dermatology. Part I: High frequency ultrasound. Eur J Dermatol 10(6):492–497PubMedGoogle Scholar
  8. 8.
    Lacarrubba F, Verzì AE, Tedeschi A, Catalfo P, Nasca MR, Micali G (2013) Clinical and ultrasonographic correlation of acne scars. Dermatol Surg 39:1683–1688PubMedCrossRefGoogle Scholar
  9. 9.
    deRigal J, Escoffier C, Querleux B, Faivre B, Agache P, Lévêque JL (1989) Assessment of aging of the human skin by in vivo ultrasonic imaging. J Investig Dermatol 93(5):621–625CrossRefGoogle Scholar
  10. 10.
    Sandby-Moller J, Wulf HC (2004) Ultrasonographic subepidermal low-echogenic band, dependence of age and body site. Skin Res Technol 10:57–63PubMedCrossRefGoogle Scholar
  11. 11.
    Gniadecka M, Jemec GBE (1998) Quantitative evaluation of chronological ageing and photoageing in vivo: studies on skin echogenicity and thickness. Br J Dermatol 139:815–821PubMedCrossRefGoogle Scholar
  12. 12.
    Gniadecka M (2001) Effects of ageing on dermal echogenicity. Skin Res Technol 7:204–207PubMedCrossRefGoogle Scholar
  13. 13.
    Waller JM, Maibach HI (2005) Age and skin structure and function, a quantitative approach (I): blood flow, thickness, and ultrasound echogenicity. Skin Res Tech 11:221–235CrossRefGoogle Scholar
  14. 14.
    Lacarrubba F, Tedeschi A, Nardone B, Micali G (2008) Mesotherapy for skin rejuvenation: assessment of the subepidermal low-echogenic band by ultrasound evaluation with crosssectional B-mode scanning. Dermatol Ther 21(Suppl. 3):S1–S5PubMedCrossRefGoogle Scholar
  15. 15.
    Pistor M (1976) What is mesotherapy? Chir Dent Fr 46:59–60PubMedGoogle Scholar
  16. 16.
    Fabbrocini G, Forgione P, Capasso C (2007) Methodologies. In: Tosti A, De Padova MP (eds) Atlas of mesotherapy in skin rejuvenation. Informa, London, p 15–23CrossRefGoogle Scholar
  17. 17.
    Tardjman M (2003) Rejeunissementcutanè du décolleté par mesotherapie. J Med Esthet Chir Dermatol 30:118Google Scholar
  18. 18.
    Galadari H, Al Faresi F (2011) Mesotherapy. Skinmed 9:342–343PubMedGoogle Scholar
  19. 19.
    Iorizzo M, De Padova MP, Tosti A (2008) Biorejuvenation: theory and practice. Clin Dermatol 26:177–181PubMedCrossRefGoogle Scholar
  20. 20.
    Tammi MI, Day AJ, Turley EA (2002) Hyaluronan and homeostasis: a balancing act. J Biol Chem 277:4581–4584PubMedCrossRefGoogle Scholar
  21. 21.
    Yoneda M, Shimizu S, Nishi Y, Yamagata M, Suzuki S, Kimata K (1988) Hyaluronic acid-dependent change in the extracellular matrix of mouse dermal fibroblasts that is conducive to cell proliferation. J Cell Sci 90:275–286PubMedGoogle Scholar
  22. 22.
    Gao F, Liu Y, He Y et al (2010) Hyaluronan oligosaccharides promote excisional wound healing through enhanced angiogenesis. Matrix Biol 29:107–116PubMedCrossRefGoogle Scholar
  23. 23.
    Savoia A, Landi S, Baldi A (2013) A new minimally invasive mesotherapy technique for facial rejuvenation. Dermatol Ther 3(1):83–93CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York and International Society of Aesthetic Plastic Surgery 2014

Authors and Affiliations

  • Aurora Tedeschi
    • 1
  • Francesco Lacarrubba
    • 1
  • Giuseppe Micali
    • 1
  1. 1.Dermatology ClinicUniversity of Catania, A.O.U. Policlinico-Vittorio EmanueleCataniaItaly

Personalised recommendations