Points to ponder on the role of polynucleotides in regenerative and aesthetic medicine: a systematic review.

Background: Polynucleotides (PDRN) have gained attention in aesthetic and regenerative medicine for their potential to enhance tissue regeneration, improve skin quality, and deliver superior aesthetic outcomes. However, the transition from theoretical benefits to proven clinical outcomes faces challenges due to inconsistencies and methodological shortcomings in the existing evidence base. This systematic review aims to critically evaluate the scientific basis and empirical evidence supporting the use of PDRN in aesthetic and regenerative medicine, highlighting the quality, reproducibility, and reliability of existing research, and identifying gaps and inconsistencies within the current literature. Methods: Adhering to PRISMA guidelines and registered with PROSPERO, this review formulated a research question using the PICO framework to assess the efficacy of PDRN applications. A comprehensive literature search across PubMed–MEDLINE, EMBASE, and Web of Science was conducted. The inclusion criteria focused on clinical studies applying PDRN in regenerative or aesthetic medicine with clear outcome measures. Quality assessment utilized Cochrane Risk of Bias tool, ROBINS-I, and Newcastle Ottawa Scale. Data synthesis was qualitative due to anticipated heterogeneity. Results: From 360 identified studies, 16 clinical trials met the inclusion criteria, encompassing various study designs and a total of 750 participants. The studies investigated PDRN's efficacy across different conditions and applications. Findings revealed a lack of specificity in PDRN sequencing, molecular targets, and dosage details, with a noted variability in source and manufacturing standards. Most studies demonstrated a low risk of bias, suggesting methodological rigor, yet the absence of comprehensive reporting on sequencing, targeted mechanisms, and molecular length was evident. The review underscores the embryonic stage of PDRN research and the necessity for more rigorous studies to validate clinical outcomes. Conclusions: The potential of PDRN in aesthetic and regenerative medicine is significant, yet the current state of evidence necessitates a cautious and evidence-based approach to their clinical integration. Future research should focus on overcoming the highlighted gaps and inconsistencies, ensuring that the innovation in treatments does not compromise patient safety and efficacy. Regulatory frameworks must evolve to address the unique challenges presented by PDRN technologies, ensuring their safe and ethical application. Level of evidence: Level I, Therapeutic. [ABSTRACT FROM AUTHOR]