Combined Hyaluronic Acid and Collagen Injections for Perioral Rejuvenation: A Randomized Controlled Trial

Abstract

ABSTRACT Background The perioral region, a critical facial aesthetic subunit, undergoes age‐related changes addressed primarily through dermal fillers. Optimal rejuvenation requires tailored approaches integrating anatomical precision, filler physicochemical properties, and standardized aging assessments. Objective To prospectively compare hyaluronic acid (HA)‐collagen combination therapy against monotherapies for perioral rejuvenation using protocol‐guided aging evaluations and personalized strategies. Methods Ninety female patients with perioral aging were randomized equally into three groups (Dec 2022–Dec 2023): Group A (HA alone), Group B (HA‐collagen), and Group C (collagen alone). Treatments were customized using baseline Comprehensive Perioral Aging Scale (CPAS) scores. Outcomes were assessed via CPAS and Global Aesthetic Improvement Scale (GAIS) posttreatment, at 3 months, and 6 months. Results Group B demonstrated statistically superior improvements in CPAS and GAIS versus monotherapy groups at all intervals ( p < 0.05). The combination regimen achieved optimal tissue support, lifting effects, and aesthetic outcomes, with sustained benefits at 6‐month follow‐up. Baseline characteristics showed no intergroup differences. Conclusion Protocol‐guided HA‐collagen synergy produces enhanced perioral rejuvenation compared to single‐agent therapies, offering improved structural support and longevity of aesthetic corrections. This randomized trial validates personalized CPAS‐based combination approaches for age‐related perioral changes.