Polydeoxyribonucleotide (PDRN) has been shown to have consistent regenerative and anti-inflammatory properties in a wide range of applications. Selective activation of the A2A receptor (A2AR) and induction of the phosphate scavenger system constitute its primary actions, which overlap the mechanism of skin regeneration after a surgical procedure; thus, PDRN can potentially be added to the post-surgical aesthetic surgery protocol of laser resurfacing, chemical peeling, microneedling, and radiofrequency. Literature search was conducted in the PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) databases with the following keywords: polydeoxyribonucleotide (PDRN) or polynucleotide, wound repair, aesthetic recovery, erythema, scar, lasers, and skin regeneration. No stipulated date limit was applied. Interventional and observational human studies, any available relevant preclinical evidence, and published systematic reviews were included. The studies were chosen based on their applicability to the biological processes of PDRN and their clinical application in skin repair situations that can be implemented in aesthetic practice. Narrative synthesis was used for thematic analysis. The pro-resolving immune reaction of PDRN works through a two-pronged mechanism: balancing the pro-inflammatory cytokine A2AR-mediated action (tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1 beta) and vascular endothelial growth factor-mediated nucleotide provisioning to growing keratinocytes and fibroblasts. There is human clinical evidence (including randomized controlled trials (RCTs), comparative cohort studies, and split-face trials) that PDRN enhances the period of re-epithelialization, erythema, scarring, and melanogenesis, which are the direct clinical outcomes with respect to post-procedural aesthetic recovery. PDRN has also shown non-inferior short-term cosmetic results compared to hyaluronic acid filler, with indications of greater biostimulatory stability. The adverse event profile in all published studies is invariably positive. The limitations of the technique, however, are a lack of RCTs (with human aesthetic cohorts), small sample sizes, variability in formulations, and a lack of long-term follow-up. Thus, the findings discussed in the current paper make PDRN an appealing and bio-plausible clinical partner in enhancing post-surgical recovery of patients undergoing aesthetic surgery. The available mechanistic and translational evidence establishes a credible biological basis for integrating PDRN into post-procedural care. On the basis of this evidence, its use may be considered a reasonable adjunct in clinical practice, subject to individual patient assessment and institutional protocol.
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