Polynucleotides and Polydeoxyribonucleotides for Skin Rejuvenation, Postoperative Scar Prevention, and Wound Healing: A Systematic Review of Randomized Clinical Trials.

Polynucleotides (PNs) and polydeoxyribonucleotides (PDRNs) are increasingly used in regenerative dermatology; however, randomized evidence across skin rejuvenation, scar prevention, and wound healing has not been comprehensively synthesized. This systematic review evaluated randomized clinical trials investigating PN- and PDRN-based interventions in these indications. PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched through January 2026. Seven randomized trials involving 183 participants met the inclusion criteria. Four studies evaluated skin rejuvenation, one postoperative scar prevention, and two wound-healing applications. Across studies, PN and PDRN therapies improved wrinkle-related outcomes, scar quality, wound-healing metrics, and patient-reported satisfaction. The most consistent benefits were observed in wound-healing settings, where PDRN accelerated re-epithelialization and shortened healing time compared with controls. No serious treatment-related adverse events were reported. Although findings support the regenerative potential of PN- and PDRN-based therapies across multiple dermatologic applications, the evidence base remains limited by small sample sizes, heterogeneous treatment protocols, and variable outcome measures. Larger, adequately powered randomized trials are needed to establish optimal clinical indications and treatment strategies.