Aesthetic Plastic Surgery

, Volume 42, Issue 6, pp 1655–1663 | Cite as

Split-Face, Randomized, Placebo-Controlled, Double-Blind Study to Investigate Passive Versus Active Dermal Filler Administration

  • Mário Jorge Freire dos Santos
  • Ricardo Carvalho
  • Luis G. ArnautEmail author
Original Article Non-Surgical Aesthetic



QueryHyaluronic acid (HA) is a large polymer increasingly used as dermal filler. HA does not permeate through healthy skin and is administered using various injection techniques. As HA procedures become more popular, the number of complications in facial rejuvenation procedures is likely to increase. Alternative methods may be necessary to satisfy the increasing demand for HA procedures. High-frequency high-intensity ultrasound is a painless and noninvasive method to deliver large molecules to the skin that is expected to deliver HA with visible results.


Assess facial rejuvenation with HA delivered with high-frequency high-intensity ultrasound.


Fifteen women (mean age 55) willing to participate in a randomized, double-blind, face-split trial with HA and placebo formulations in different sides of the face, were subject to five treatment sessions with high-frequency high-intensity ultrasound. Photographs taken before the procedure and after the last procedure were evaluated by a panel of five experts, blind to which side was treated with the HA or with the placebo.


The expert panel identified a noticeable facial rejuvenation in the HA side relative to the placebo with a very statistically significant difference between the two sides (p < 0.0001).


Administration of HA with high-frequency high-intensity ultrasound is safe and leads to unambiguous facial rejuvenation.

Level of Evidence I

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


Hyaluronic acid Rejuvenation Wrinkles High-frequency ultrasound Penetration enhancement Piezoporation 



The authors wish to thank Dr. Gonçalo Sá and Ângela Correia for assistance with the ex vivo studies. Funding was provided by Fundação para a Ciência e a Tecnologia (Grant No. 007630UID/QUI/00313/2013), H2020 Research Infrastructures (Grant No. LASERLAB EUROPE 654148).

Compliance with Ethical Standards

Conflict of interest

LGA holds intellectual property rights and equity related to the technology for active dermal filler administration. MJFS and RC declare that they have no conflicts of interest.

Ethical Standards

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery 2018

Authors and Affiliations

  1. 1.Cirurgia PlásticaCentro Cirúrgico de CoimbraCoimbraPortugal
  2. 2.Unit of Plastic and Reconstructive Surgery and Burns UnitUniversity of Coimbra HospitalsCoimbraPortugal
  3. 3.Centro de Cirurgia Plástica e EstéticaSanfilCoimbraPortugal
  4. 4.Chemistry DepartmentUniversity of CoimbraCoimbraPortugal

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