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

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).

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.

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.

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.