Authors: Martina Ponzo, MD , Mariagiovanna Lombardi, MD , Stefano Avvedimento, MD , Federico M D'Alessio, MD , Maurizio Cavallini, MD , Adriano Santorelli, MD
Abstract: Poly-L-lactic acid (PLLA) is a biostimulatory injectable that restores midfacial volume through collagen neogenesis rather than gel-based filling. Controlled clinical evidence directly quantifying PLLA's volumetric efficacy remains limited. This study aimed to evaluate the efficacy, safety, and patient-reported outcomes of a Norberg Medical PLLA formulation for midface rejuvenation in a prospective, evaluator-blinded, split-face controlled study. Participants were enrolled between July 2024 and September 2024, with follow-up completed in September 2025. Ninety-five patients underwent three standardized PLLA sessions on one hemiface and saline placebo on the contralateral side. Each vial contained 150 mg PLLA in spherical microparticles, reconstituted with 5 mL sterile water without lidocaine. Assessments included Wrinkle Severity Rating Scale (WSRS), Vectra H1 3D volumetry (malar, zygomatic, mandibular), FACE-Q, and Global Aesthetic Improvement Scale (GAIS). Two blinded evaluators rated WSRS. Statistical analysis included paired testing, responder rates (≥1-grade WSRS improvement), and inter-rater reliability (ICC). At 12 months, PLLA-treated sides showed significant WSRS reduction vs baseline and saline control (Δ = −0.68, P < .001). 3D analysis confirmed sustained volumetric enhancement across all midface subunits. Inter-rater reliability was excellent (ICC = 0.91), and 82.1% achieved ≥1-grade WSRS improvement. Patient satisfaction remained high, mirroring objective findings. Adverse events were mild and transient, with no granulomas, nodules, or vascular events recorded. Controlled split-face evaluation demonstrated that standardized PLLA treatment yields measurable, long-lasting midfacial volume restoration with excellent safety and high patient satisfaction. No granulomas or delayed-onset nodules were observed in this 12-month, 95-patient cohort, supporting a favorable safety profile for this PLLA formulation under these study conditions.
