Evidence map›Paper›PMID 39989893›Full record

ArticlePlastic and reconstructive surgery. Global open2025

Safety and Performance of RHA4 in the Midface Using the Multilayering Technique: Preclinical and Clinical Evidence.

Killian Flégeau, Stefania Ballarini, Romain Brusini, Camille Vantou, Zhifeng Liao, Nathalie Hirt-Burri, François Bourdon, Fang-Wen Tseng, Jimmy Faivre

Abstract read
In one paragraph

Article in Plastic and reconstructive surgery. Global open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Debunking Myths on Hyaluronic Acid Injectable Gels in Clinical Practice.Plastic and reconstructive surgery. Global open · 2026
    Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Killian FlégeauFrom the Research and Development Department, Teoxane SA, Geneva, Switzerland.
Stefania BallariniMedical Affairs Department, Teoxane SA, Geneva, Switzerland.
Romain BrusiniFrom the Research and Development Department, Teoxane SA, Geneva, Switzerland.
Camille VantouFrom the Research and Development Department, Teoxane SA, Geneva, Switzerland.
Zhifeng LiaoRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, Epalinges, Switzerland.
Nathalie Hirt-BurriRegenerative Therapy Unit, Lausanne University Hospital, University of Lausanne, Epalinges, Switzerland.
François BourdonFrom the Research and Development Department, Teoxane SA, Geneva, Switzerland.
Fang-Wen TsengEverbeaute Medical Aesthetics, Taipei, Taiwan.
Jimmy FaivreFrom the Research and Development Department, Teoxane SA, Geneva, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Resilient hyaluronic acid (RHA) fillers are used to treat dynamic wrinkles or provide tissue lifting in facial aesthetics. This study explored the biological, biomechanical, and clinical safety and performance of RHA4, a volumizing hyaluronic acid filler tailored for tissue support in dynamic facial areas, upon interaction with human subcutaneous adipose tissue (AT). Methods: RHA4 underwent cytocompatibility testing with human fibroblasts and adipose stem cells. A 1-year rat in vivo implantation study tracked tissue integration, local effects, and filler degradation. Biomechanical tests assessed RHA4's impact on subcutaneous AT mechanics. Clinical outcomes, safety, injection volumes, and techniques were evaluated in 35 patients, treated in midface deep and superficial fat compartments via a multilayering methodology. Dynamic outcomes and 2-year follow-up of RHA4 in the midface using multilayer treatments were described. Results: RHA4 demonstrated excellent biocompatibility and tissue integration both in vitro and in vivo, exhibiting minimal local inflammation and rapid collagen bundle formation within the filler. It integrated gradually over time and was well tolerated, allowing for increased extracellular matrix presence, neovascularization, denser collagen deposition, and AT growth. Ex vivo, RHA4 did not impede fat motion biomechanics but visibly lifted the tissue. Clinically, RHA4 proved safe and effective for lifting both deep and superficial fat compartments in the midface without affecting facial expressiveness. Conclusions: Preclinical and clinical evidence confirmed that RHA4 is a versatile filler capable of lifting tissue efficiently, whether deep or superficial, particularly through the multilayering treatment approach. Importantly, RHA4 preserves AT biomechanics, adapts to the dynamism of the face, and ensures natural-looking outcomes.

Identifiers

PMID39989893
PMCPMC11845203

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.