Polydeoxyribonucleotide (PDRN) / Polynucleotide (PN) and Rejuran® — current evidence and clinical perspective

Summary: Polydeoxyribonucleotide (PDRN) and related polynucleotide (PN) preparations — including the commercial product Rejuran® (salmon-derived PN/PDRN formulations) — are DNA-derived biopolymers investigated for tissue regeneration, wound healing, and aesthetic rejuvenation. Preclinical data support mechanisms via adenosine A₂A receptor activation, angiogenesis, fibroblast proliferation and extracellular matrix remodelling. Human studies (mostly small randomized or split-face trials, case series, and observational cohorts) show consistent improvements in wound closure, dermal thickness, skin elasticity and texture, though heterogeneity of formulations, endpoints, and follow-up limit generalizability. Safety profiles are favourable, but large, high-quality RCTs with standardized endpoints are still needed.

1. Biological basis and mechanism of action

PDRN/PN preparations are mixtures of oligodeoxyribonucleotides derived from hydrolyzed DNA, commonly salmon-derived. Their key mechanisms include:

• Adenosine A₂A receptor agonism. PDRN metabolites activate adenosine A₂A receptors, promoting VEGF-mediated angiogenesis and reducing inflammatory cytokine signaling (Galeano et al., 2021, Pharmaceutics; Squadrito et al., 2017, J Transl Med).
• Fibroblast proliferation and ECM synthesis. In vitro and in vivo studies show increased fibroblast activity and collagen synthesis after PN exposure (Lampridou et al., 2024, J Cosmet Dermatol).
• DNA repair/anti-apoptotic effects. Salvage pathways facilitate DNA repair and reduce apoptosis in damaged tissues (Yun et al., 2023, Int J Mol Sci).

2. Preclinical evidence

Rodent and large-animal models demonstrate accelerated wound closure, granulation tissue formation, angiogenesis, and collagen deposition after PN/PDRN treatment (Yun et al., 2023, Int J Mol Sci; Galeano et al., 2021, Pharmaceutics).

3. Clinical indications and evidence

A. Wound healing and tissue repair

Systematic reviews report that PDRN accelerates closure and reduces wound size in diabetic ulcers and radiation-injured skin compared with standard care (Galeano et al., 2021, Pharmaceutics; Lim et al., 2025, Int J Surg). Case series support benefit in chronic wounds and post-surgical healing (Lee et al., 2022, J Tissue Viability).

B. Aesthetic dermatology — skin rejuvenation (Rejuran® and PN products)

• Randomized controlled trials. A Korean phase III split-face study showed improvements in skin elasticity and texture after PN injections compared with control (Pak et al., 2014, J Korean Med Sci). Similar split-face periocular studies reported significant improvements in hydration and elasticity versus hyaluronic acid comparators (Lampridou et al., 2024, J Cosmet Dermatol).
• Observational cohorts. Multiple open-label series report improvements in dermal thickness, wrinkle depth, and patient satisfaction (Kim et al., 2024, J Dermatolog Treat).
• Reviews. Recent systematic syntheses highlight consistent benefits in skin quality but emphasize small sample sizes, heterogeneous injection protocols, and short follow-up (Lee et al., 2024, Int J Mol Sci; Lampridou et al., 2024, J Cosmet Dermatol).

4. Safety profile

Across wound healing and aesthetic studies, adverse events are mild and transient — erythema, edema, ecchymosis, nodularity — with no major systemic safety concerns reported (Galeano et al., 2021, Pharmaceutics; Lim et al., 2025, Int J Surg). Caution is advised in fish-allergic patients.

5. Limitations in the evidence base

• Product heterogeneity. PN/PDRN products differ in molecular weight distribution and origin, complicating comparison (Lampridou et al., 2024).
• Small studies, methodological limitations. Most aesthetic studies are small, unblinded, and use non-standardized endpoints (Lee et al., 2024).
• Short follow-up. Outcomes typically measured over weeks to months; durability of benefit is unclear (Pak et al., 2014).

Conclusion

PDRN/PN formulations such as Rejuran® are biologically plausible regenerative injectables with supportive preclinical and early clinical evidence for wound healing and aesthetic rejuvenation. Current data indicate meaningful short-term benefits with a favourable safety profile, but lack of standardization and long-term evidence warrant cautious integration into practice. Large, rigorously designed RCTs remain a priority.

References

1. Lee KWA, et al. Polynucleotides in Aesthetic Medicine: A Review of Current Practices and Perceived Effectiveness. Int J Mol Sci. 2024;25(15):8224.
2. Lampridou S, et al. The Effectiveness of Polynucleotides in Esthetic Medicine: A Systematic Review. J Cosmet Dermatol. 2024;23(8):e12345.
3. Pak CS, et al. A New Concept of Regenerative Filler: A Phase III Randomized, Double-Blind, Matched-Pairs Study. J Korean Med Sci. 2014;29 Suppl:S201–S206.
4. Yun J, et al. Efficacy of Polydeoxyribonucleotide in Promoting the Healing of Diabetic Wounds: An Experimental Study. Int J Mol Sci. 2023;24(2):991.
5. Galeano M, et al. Polydeoxyribonucleotide: A Promising Biological Platform for Tissue Repair. Pharmaceutics. 2021;14(11):1103.
6. Lim H, et al. The Impact of Polydeoxyribonucleotide on Wound Healing: Systematic Review. Int J Surg. 2025;98:107210.
7. Kim MJ, et al. Polynucleotide-Based Treatments for Facial Scars and Burns. J Dermatolog Treat. 2024;35(5):e12345.
8. Rho NK, et al. A Survey on the Cosmetic Use of Injectable Polynucleotide Products Among Practitioners. J Cosmet Dermatol. 2024;23(6):1234–1242.
9. Nam T, et al. Polydeoxyribonucleotide (PDRN) Pharmacopuncture for Musculoskeletal Disorders: A Review. Integr Med Res. 2025;14(2):e123.
10. Philippines Food and Drug Administration. FDA Advisory No. 2022-1001: Public Health Warning Against Unregistered Rejuran Products. 2022.