Assessment of Safety and Tissue Integration of PEGDE-Based Hyaluronic Acid Filler for Severe Nasolabial Folds: A Prospective Observational Study with Biophysical and Ultrasound Evaluation

Abstract

Hyaluronic acid (HA) fillers represent the most frequently performed minimally invasive procedures for facial rejuvenation, yet their overall safety profile is critically influenced by the cross-linking technology employed. Polyethylene glycol diglycidyl ether (PEGDE) has recently been introduced as an alternative to 1,4-butanediol diglycidyl ether (BDDE). The present prospective observational study was undertaken to evaluate the safety of a PEGDE-crosslinked HA filler for the correction of severe nasolabial folds. A total of 60 patients received bilateral injections of 1 mL per side and were monitored over a six-month period. Safety assessment included systematic documentation of adverse events and non-invasive biophysical and imaging techniques, specifically corneometry, sebumetry, and high-frequency ultrasound (HFUS). The treatment was well tolerated: 15% of patients reported only mild and transient adverse events, such as pain, swelling, bruising, or discomfort, while no serious adverse events, vascular compromise, or ocular complications were observed. Corneometry demonstrated a statistically significant increase in cutaneous hydration, sebumetry confirmed stability of sebaceous activity, and HFUS documented correct placement, homogeneous distribution, and progressive integration of the filler without nodules or granulomatous reactions. These findings support the favorable short-term safety and local tolerance of PEGDE-crosslinked HA fillers in the treatment of severe nasolabial folds.