# A Novel Technology to Boost Natural Production of Hyaluronic Acid in the Skin Tissue: Human Histology Study

**Authors:** David J. Goldberg

PMC · DOI: 10.1111/jocd.70159 · 2025-04-17

## TL;DR

This study shows that combining radiofrequency and ultrasound treatments boosts hyaluronic acid production in the skin, leading to better facial rejuvenation.

## Contribution

The study introduces a novel combination of RF and TUS for enhanced and sustained HA production in human skin.

## Key findings

- The RF+TUS group showed a 67.69% increase in HA-stained area at 3 months.
- RF alone showed only a 9.56% increase in HA-stained area at 3 months.
- Digital photos showed reduced rhytids and tighter skin in the RF+TUS group.

## Abstract

Combining monopolar radiofrequency (RF) with targeted ultrasound (TUS), this study investigated whether these modalities promote facial rejuvenation through the production of hyaluronic acid (HA) in human skin.

Seven subjects (51–64 years, BMI 21.1–29.8 kg/m2) were enrolled and divided into three treatment groups in this single‐center study; Group A (n = 3, simultaneous RF + TUS), Group B (n = 3, stand‐alone RF), and control (n = 1, no treatment). Both treated groups underwent four (4) 60‐min treatments on the face delivered 7–14 days apart. Punch biopsies (3 mm in diameter) were collected from the infra‐auricular area at baseline and both follow‐up visits and stained for HA by using hyaluronic acid binding protein. Digital photographs were taken to document changes in visual appearance. Finally, the subjects' comfort and satisfaction were assessed.

There was a statistically significant (p < 0.05) average increase at 1 month in the HA‐stained area of +112 358.7 μm2 in group A (RF + TUS) representing an increase of 48.65%. The treatment effect peaked at 3 months with an increase of +156 345.2 μm2, corresponding to a 67.69% increase in the HA‐stained area. In Group B, there was no significant difference in the average increase of the HA‐stained area between 1 month (+14 830 μm2) and 3 months (+20 995 μm2) corresponding to a 6.76% and 9.56% increase, respectively. The control samples did not indicate any changes throughout the study. Digital photographs of the RF + TUS group showed both a decrease in rhytids and tighter skin. Therapies were comfortable with no adverse events.

Overall, this study has shown that the combination treatment of RF + TUS has a more pronounced and sustained effect on facial rejuvenation compared to RF alone. The measurable increase in the production of HA with simultaneous use of RF + TUS peaked at a 3‐month follow‐up, suggesting the gradual advancement of the treatment effect and overall improvement in facial appearance.

ClinicalTrials.gov identifier: NCT05987917

## Linked entities

- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Chemicals:** HA (MESH:D006820)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12004441/full.md

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Source: https://tomesphere.com/paper/PMC12004441