Background: Facial atrophic acne scars have a significant impact on patients’ psychosocial well-being and remain a therapeutic challenge. Existing treatments options are frequently limited by modest efficacy and adverse effects. The combination of Polynucleotide High-Purification Technology (PN HPT™) and hyaluronic acid (HA) represents a novel bioregenerative strategy aimed at improving dermal remodelling and overall skin quality. Methods: This six-month, prospective, real-world study evaluated the efficacy and safety of Newest® (Mastelli S.r.l., Sanremo, Italy), a sterile intradermal gel containing highly purified polynucleotides (10 mg/mL) and HA (10 mg/mL). Eligible participants, aged 20–60 years with moderate-to-severe atrophic facial post-acne scars, underwent four treatment sessions in two-week intervals. Efficacy was assessed using the Acne Scar Assessment Scale (ASAS) and Global Aesthetic Improvement Scale (GAIS) at three and six months, while safety was monitored throughout the study. Results: A total of 62 patients (32 Caucasian, 30 Asian; 19 males, 43 females; mean age: 36.6 years) completed the study. At three and six months, 46.8% showed at least a one-grade reduction in ASAS score with respect to the baseline. Patient-reported GAIS indicated that 54.8% perceived an improvement in scar appearance, aligning with investigator assessments. Only one mild, transient adverse event (wheal formation) occurred, which resolved spontaneously without intervention. Conclusions: In this real-world study, treatment with Polynucleotide High-Purification Technology (10 mg/mL) combined with HA (10 mg/mL) was associated with observable improvementin atrophic facial acne scars, with an excellent safety and tolerability profile. These findings support the potential of polynucleotide-based therapies for use as welltolerated options for managing moderate-to-severe atrophic acne scarring, while the need for further controlled studies to confirm efficacy is also acknowledged.
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