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Cited by 18Wound Healing and TreatmentsFacial Rejuvenation and Surgery TechniquesSkin Protection and Aging

Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives

Open access
Kim, Sung Tae·2025·Pharmaceutics
DOI 10.3390/pharmaceutics17081024PMC PMC12388916
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Abstract

Polynucleotide (PN) and polydeoxyribonucleotide (PDRN) are DNA-derived biopolymers increasingly recognized for their potential in dermatology. Despite their structural similarities, PN and PDRN exhibit distinct functions due to differences in polymer length and molecular weight. PN, composed of longer DNA fragments, plays a key role in extracellular matrix remodeling. Conversely, PDRN, composed of relatively shorter oligonucleotide sequences than those of PN, enhances skin condition through adenosine receptor activations and supports nucleotide synthesis via both the salvage and de novo pathways. This review provides a critical comparison of the molecular characteristics and functions of PN and PDRN with particular emphasis on their dermatological applications. By delineating their respective roles in esthetic and regenerative medicine, we aim to highlight recent advances that may guide the development of optimized treatment strategies and foster evidence-based clinical practice.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review compares polynucleotide (PN) and polydeoxyribonucleotide (PDRN), two DNA-derived biopolymers used in dermatology, arguing that they differ in chain length, molecular weight, and mechanism despite frequent interchangeable use in the literature. It concludes that PN acts mainly as a structural/rheological support agent while PDRN behaves as a pharmacologically active molecule via adenosine A2A receptor activation and the nucleotide salvage pathway.

Key findings

  • PN, derived mainly from fish testes (salmon/trout), consists of longer chains, forms a more porous, highly viscous three-dimensional structure, and is used as a skin booster, filler, and intra-articular injection; it is often combined with hyaluronic acid (HA), with cited studies reporting HA+PN combinations outperforming HA alone.
  • PDRN, extracted from fish sperm (e.g., *Oncorhynchus mykiss*, *Oncorhynchus keta*), has shorter chains and lower viscoelasticity; it acts through selective adenosine A2A receptor activation (modulating NF-κB and MAPK pathways, upregulating VEGF and IL-10, downregulating TNF-α, IL-6, HMGB1, IL-1β, and MMP-1) and through salvage-pathway nucleotide recycling.
  • Reported PDRN dermatological effects include fibroblast and osteoblast proliferation, wound healing, angiogenesis, anti-inflammation, hypopigmentation via ERK/PI3K-AKT-mediated MITF suppression, and antioxidant activity (NRF2/HO-1 suggested); hair regrowth evidence comes from co-treatment with platelet-rich plasma or fractionated thulium laser.
  • Regulatory status differs: in Korea PDRN is approved for graft-induced wounds and tissue regeneration and as a prescription injectable (also for knee osteoarthritis), while PN is designated a medical device; PN is also used in the EU, Malaysia, Thailand, and Australia. No standardized molecular-weight thresholds distinguish PN from PDRN.

Methods

  • Narrative review; literature identified via searches of PubMed, Google, Google Scholar, and Web of Science, limited to English-language publications up to May 2025, selecting studies on polynucleotides and polydeoxyribonucleotides.
  • No systematic review protocol, meta-analysis, or primary data collection is described; the paper synthesizes molecular, in vitro, animal, and clinical literature and includes a comparison table (Table 1) and two mechanistic figures.

Limitations

  • Stated by the authors: interchangeable use of the terms PN and PDRN in the literature, broad and overlapping molecular-weight ranges and distributions, varying purification methods, and research concentrated in a limited number of countries with differing regulatory frameworks, all of which hinder cross-national comparison and generalization.
  • Stated by the authors: no standardized criteria exist to delineate molecular-weight thresholds distinguishing PN from PDRN, and distinctions are often defined solely by manufacturers based on undisclosed proprietary technologies (e.g., Mastelli's HPT, PharmaResearch's DOT).
  • Evident in the text: antioxidant evidence derives primarily from RAW264.7 macrophage models rather than skin cells, and the authors note limited clinical data for hair regeneration and limited research on PDRN's dermatological anti-inflammatory effects; alternative (plant, microbial, seaweed) sources remain early-stage.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/pharmaceutics17081024

Cites

175 of 175 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

137 of 218 cited sources checked · 21 supported · 3 flagged · accuracy not yet measured

  • Premisecitation

    In a randomized, double-blind, split-face trial, PN-based fillers demonstrated superior outcomes to HA fillers in improving skin roughness, pore size, and hydration.

    “Notably, in a randomized, double-blind, split-face trial, PN-based fillers demonstrated superior outcomes to those of HA fillers in terms of improving skin roughness, pore size, and hydration.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [14] Rho, 2023, A survey on the cosmetic use of injectable polynucleotide: The pattern of practice among Korean Dermatologists, J. Cosmet. Dermatol. source

      The References section (page unavailable) lists a randomized, double-blind, split-face trial comparing PN and HA fillers, but gives no results. The Discussion and survey Results (pages unavailable) do not report whether PN was superior for skin roughness, pore size, or hydration; searches for those outcomes found no such comparison in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [170] Yogya, 2022, Efficacy and Safety of Using Noninsulated Microneedle Radiofrequency Alone versus in Combination with Polynucleotides for Treatment of Periorbital Wrinkles, Dermatol. Ther. source

      The Methods describe a randomized, double-blind, split-face study, but the comparison was topical PN-containing serum versus normal saline after radiofrequency microneedling—not PN fillers versus HA fillers. The Methods and Results assess periorbital wrinkles, not skin roughness, pore size, or hydration. The serum itself contained HA, so the paper cannot establish PN superiority over HA. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Interpretationcitation

    PDRN exhibits lower viscoelasticity than PN because of its reduced molecular weight.

    “However, PDRN exhibits lower viscoelasticity than that of PN because of its reduced molecular weight, whereas PN forms a more porous, highly viscous, three-dimensional structure [11,24,25].”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [11] Marques, C., Porcello, A., Cerrano, M., Hadjab, F., Chemali, M., Lourenço, K., Hadjab, B., Raffoul, W., Applegate, L.A., and Laurent, A.E. (2025). From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules. Biomolecules, 15. source

      Section 5 describes PDRN as generally having a lower molecular weight than PN, calls PN viscoelastic, and links PN’s high molecular weight to high-viscosity hydrogels. The Conclusions also say viscosity can vary with the final molecular weight of a formulation. The paper does not directly establish that PDRN is less viscoelastic than PN as a general comparison. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [24] Kim, M.J., Park, H., Jung, R., Won, C., Ohk, S., Kim, H., Roh, N., and Yi, K. (2024). High-resolution 3-D scanning electron microscopy (SEM) images of DOT™ polynucleotides (PN): Unique scaffold characteristics and potential applications in biomedicine. Ski. Res. Technol., 30. source

      The Discussion (page not specified) states that DOT™ PDRN has a lower molecular weight than DOT™ PN, and the Results describe distinct structural differences. The paper does not report a viscoelasticity comparison or establish that molecular weight causes one, so that part of the claim is unsupported. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [25] Kim, 2023, Polynucleotide injection treatment for iatrogenic fat atrophy in two patients: Potential for safe volumization in aesthetic medicine, Ski. Res. Technol. source

      The paper describes high-viscosity PN injections and a three-dimensional scaffold (CASE 2; page unavailable), but does not compare PN with PDRN on viscoelasticity. Searches for the comparison and for molecular weight found no passage saying that PDRN has lower molecular weight or that this causes lower viscoelasticity. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
  • Premisecitation

    PN contributes to creating a favorable microenvironment that supports extracellular matrix production and overall tissue revitalization.

    “From a regenerative perspective, PN contributes to creating a favorable microenvironment that supports extracellular matrix (ECM) production and overall tissue revitalization [29,30].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [29] Lee, 2024, Assessment of current practices and perceived effectiveness of injectable polynucleotide for enlarged facial pores among cosmetic physicians: A survey-based evaluation, Ski. Res. Technol. source
    • cites [30] Oh, N., Hwang, J., Kang, M.S., Yoo, C.-Y., Kwak, M., and Han, D.-W. (2025). Versatile and Marvelous Potentials of Polydeoxyribonucleotide for Tissue Engineering and Regeneration. Biomater. Res., 29. source
  • Premisecitation

    Both PN and PDRN are nucleic acid-derived polymers composed of nucleotide monomers connected via phosphodiester bonds.

    “Both PN and PDRN are nucleic acid-derived polymers composed of nucleotide monomers connected via phosphodiester bonds [11,17].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [11] Marques, C., Porcello, A., Cerrano, M., Hadjab, F., Chemali, M., Lourenço, K., Hadjab, B., Raffoul, W., Applegate, L.A., and Laurent, A.E. (2025). From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules. Biomolecules, 15. source

      The Introduction and Section 2 describe both PDRN and PN as DNA-derived polymers made of deoxyribonucleotide units. Our copy does not specify that the units are connected by phosphodiester bonds, so that detail is not directly supported by this source. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [17] Khan, 2022, Polydeoxyribonucleotide: A promising skin anti-aging agent, Chin. J. Plast. Reconstr. Surg. source

      The Introduction states that PDRN is a DNA-derived linear polymer of deoxyribonucleotide monomers joined by phosphodiester linkages. The paper also mentions polynucleotide-containing products, but the passages found do not separately describe PN’s composition or linkages, so the claim about both is only partly supported. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    PN forms a more porous, highly viscous, three-dimensional structure.

    “However, PDRN exhibits lower viscoelasticity than that of PN because of its reduced molecular weight, whereas PN forms a more porous, highly viscous, three-dimensional structure [11,24,25].”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [11] Marques, C., Porcello, A., Cerrano, M., Hadjab, F., Chemali, M., Lourenço, K., Hadjab, B., Raffoul, W., Applegate, L.A., and Laurent, A.E. (2025). From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules. Biomolecules, 15. source

      Section 5 says PN is used to make hydrogels with high viscosity. Section 6 describes a scaffolded, polygonal structure in a PN-based hydrogel, but does not establish that it is more porous than PDRN or explicitly characterize that PN structure as three-dimensional. Page numbers are unavailable in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [24] Kim, M.J., Park, H., Jung, R., Won, C., Ohk, S., Kim, H., Roh, N., and Yi, K. (2024). High-resolution 3-D scanning electron microscopy (SEM) images of DOT™ polynucleotides (PN): Unique scaffold characteristics and potential applications in biomedicine. Ski. Res. Technol., 30. source

      The Results (page not available in our copy) describe DOT™ PN as a scaffold whose walls enclose three-dimensional spaces, in contrast to the amorphous structure observed for PDRN. They do not establish that PN is more porous or highly viscous; the paper describes the sample as gel-like but reports no viscosity comparison. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [25] Kim, 2023, Polynucleotide injection treatment for iatrogenic fat atrophy in two patients: Potential for safe volumization in aesthetic medicine, Ski. Res. Technol. source

      The CASE 2 passage (page not specified) describes high-viscosity PN injections and a 3-D scaffold structure. It does not describe the structure as porous, so that part of the attributed claim is unsupported. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • May combine two claims. 41
  • Classified as probably not a substantial claim. 29

  • May combine two claims.

    Premisecitation

    Quiescent and differentiated cells preferentially utilize the salvage pathway, while highly proliferative cells depend more heavily on nucleotide biosynthesis.

    “While quiescent and differentiated cells preferentially utilize the salvage pathway, highly proliferative cells depend more heavily on nucleotide biosynthesis [79].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [79] Tran, 2024, De novo and salvage purine synthesis pathways across tissues and tumors, Cell source

      The Introduction presents this contrast as a historical belief, not an established finding. The Discussion says the study challenges the notion that proliferating tumors predominantly rely on de novo synthesis: de novo and salvage pathways contribute similarly to their purine nucleotide pools. The cited paper therefore does not support stating the contrast as fact. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In the periorbital region, PN injections were well-tolerated and associated with minimal side effects.

    “These benefits were particularly evident in the periorbital region, where PN injections were well-tolerated and associated with minimal side effects [14,170].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [14] Rho, 2023, A survey on the cosmetic use of injectable polynucleotide: The pattern of practice among Korean Dermatologists, J. Cosmet. Dermatol. source

      The Discussion describes PN injections as causing a fair amount of discomfort and says lateral canthal lines are prone to bruising. It also mentions bumps and downtime from intradermal injection. Although the survey identifies periorbital fine lines as an indication for PN, it does not characterize injections there as well-tolerated with minimal side effects. (LLM, conf=0.84)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [170] Yogya, 2022, Efficacy and Safety of Using Noninsulated Microneedle Radiofrequency Alone versus in Combination with Polynucleotides for Treatment of Periorbital Wrinkles, Dermatol. Ther. source

      The Abstract Results report low average pain and no serious adverse events, and the Conclusions describe the combined treatment as safe for periorbital wrinkles. However, the Methods identify the PN product as topical serum applied after radiofrequency microneedling, not a PN injection; the paper therefore does not establish that PN injections were well-tolerated. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    PN has shown benefits for skin health, including improving skin texture and elasticity, and reducing wrinkle depth.

    “In dermatology, PN, primarily derived from fish testes, has shown promising benefits for skin health, including improving skin texture and elasticity, and reducing wrinkle depth [26,27,28].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [26] Colangelo, M.T., Belletti, S., Govoni, P., Guizzardi, S., and Galli, C. (2021). A Biomimetic Polynucleotides–Hyaluronic Acid Hydrogel Promotes Wound Healing in a Primary Gingival Fibroblast Model. Appl. Sci., 11. source

      The Materials section identifies salmon trout gonads as the source of the PN used, and the Introduction describes PN use in dermal fibroblast models and skin wound healing. Neither those passages nor the passages found by searching for texture, elasticity, and wrinkles report improvements in skin texture or elasticity or reduced wrinkle depth; the study itself uses a gingival fibroblast model. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [27] Pitassi, 2024, Polynucleotides in Skin Regeneration: Targeting the Adenosine A2A Receptor and Salvage Pathway, Dermatol. Surg. source
    • cites [28] Cavallini, 2024, Value and Benefits of the Polynucleotides HPT™ Dermal Priming Paradigm A Consensus on Practice Guidance for Aesthetic Medicine Practitioners and Future Research, Clin. Exp. Dermatol. Ther.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PDRN is composed of a linear structure of deoxyribonucleotides linked by phosphodiester bonds, which is double stranded.

    “PDRN, similar to PN, is composed of a linear structure of deoxyribonucleotides linked by phosphodiester bonds, which is double stranded [11,23].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [11] Marques, C., Porcello, A., Cerrano, M., Hadjab, F., Chemali, M., Lourenço, K., Hadjab, B., Raffoul, W., Applegate, L.A., and Laurent, A.E. (2025). From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules. Biomolecules, 15. source

      The Introduction describes PDRN and PN as DNA fragments composed of deoxyribonucleotide units and measured in base pairs. Section 2 calls them chains of deoxyribonucleotides and describes DNA as a double helix. The copy does not specify that the units are linked by phosphodiester bonds, so that detail is not supported by this source. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [23] Galeano, M., Pallio, G., Irrera, N., Mannino, F., Bitto, A., Altavilla, D., Vaccaro, M., Squadrito, G., Arcoraci, V., and Colonna, M.R. (2021). Polydeoxyribonucleotide: A Promising Biological Platform to Accelerate Impaired Skin Wound Healing. Pharmaceuticals, 14. source

  • May combine two claims.

    Premisecitation

    Owing to its high water content, PN forms a hydrogel that improves hydration and restores skin viscosity.

    “Owing to its high water content, PN forms a hydrogel that improves hydration and restores skin viscosity [31,32,33].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [31] Kim, 2020, Comparison of the effects of polynucleotide and hyaluronic acid fillers on periocular rejuvenation: A randomized, double-blind, split-face trial, J. Dermatol. Treat.

      Not checked in the free run.

    • cites [32] Ha, 2024, The Effect of Polynucleotide-Hyaluronic Acid Hydrogel in the Recovery After Mechanical Skin Barrier Disruption, Ski. Res. Technol. source
    • cites [33] Titcomb, 2025, A literature review on polynucleotide efficacy on skin rejuvenation, and review of the regulatory status and guidelines around polynucleotides, J. Aesthetic Nurs. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PDRN sources mainly include the sperm of Oncorhynchus mykiss and Oncorhynchus keta.

    “Furthermore, its sources mainly include the sperm of species such as Oncorhynchus mykiss (salmon trout) and Oncorhynchus keta (chum salmon) [11,19].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [11] Marques, C., Porcello, A., Cerrano, M., Hadjab, F., Chemali, M., Lourenço, K., Hadjab, B., Raffoul, W., Applegate, L.A., and Laurent, A.E. (2025). From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules. Biomolecules, 15. source
    • cites [19] Squadrito, 2017, Pharmacological Activity and Clinical Use of PDRN, Front. Pharmacol. source

  • May combine two claims.

    Premisecitation

    In Korea, PDRN is approved for the treatment of graft-induced wounds and tissue regeneration, whereas PN is designated as a medical device.

    “In Korea, PDRN is approved for the treatment of graft-induced wounds and tissue regeneration [48,152,153], whereas PN is designated as a medical device [154].”
    Quote in the paperNot a substantial claim1 of 4 sources checked
    • cites [48] Kim, T.-H., Heo, S.-Y., Oh, G.-W., Heo, S.-J., and Jung, W.-K. (2021). Applications of Marine Organism-Derived Polydeoxyribonucleotide: Its Potential in Biomedical Engineering. Mar. Drugs, 19. source

      The Introduction (page unavailable) says PDRN is approved by the Korea Food and Drug Administration and used in tissue repair and wound treatment. Section 2.3 (page unavailable) reports improved composite-graft survival, but does not say that graft-induced wounds are an approved indication. The PN medical-device designation is attached to a different citation [154] and is not assessed here. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [152] (2025, June 23). Drug Approval by MFDS, Drug Information, Announcement of Drug Master File (DMF) Registration: Search by ingredient-Sodium polydeoxyribonucleotide, Available online: https://nedrug.mfds.go.kr/.

      Not checked in the free run.

    • cites [153] (2025, June 23). EMEDI: Information Search-REJURAN, Available online: https://emedi.mfds.go.kr/search/data/MNU20237#item.

      Not checked in the free run.

    • cites [154] (2025, June 23). EMEDI: Information Search-Polydeoxyribonucleotide, Available online: https://emedi.mfds.go.kr/search/data/MNU20237#item.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Alternative biological source approaches for PDRN production tend to be more complex.

    “although these approaches tend to be more complex”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [134] Shu, Z., Ji, Y., Liu, F., Jing, Y., Jiao, C., Li, Y., Zhao, Y., Wang, G., and Zhang, J. (2024). Proteomics Analysis of the Protective Effect of Polydeoxyribonucleotide Extracted from Sea Cucumber (Apostichopus japonicus) Sperm in a Hydrogen Peroxide-Induced RAW264.7 Cell Injury Model. Mar. Drugs, 22. source

      The Introduction identifies common PDRN sources, and Materials and Methods §4.2 describes extraction from sea cucumber sperm. Neither passage compares the complexity of alternative-source approaches with conventional production, so the claimed tendency cannot be verified from this paper. (LLM, conf=0.73)

      Experimental — accuracy not yet measured
    • cites [163] Cheng, 2016, An update review on recent skin fillers, Plast. Aesthetic Res. source

      The Platelet-rich plasma section describes preparing PRP from blood, not producing PDRN. Searches for PDRN, polydeoxyribonucleotide, alternative biological sources, and production complexity found no passage addressing the claim in our copy; page numbers were not available. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [164] Cavallini, 2020, Consensus report on the use of PN-HPT™ (polynucleotides highly purified technology) in aesthetic medicine, J. Cosmet. Dermatol. source

      The Background section identifies trout gonads as a source of purified polynucleotides, but does not compare biological sources or discuss the complexity of PDRN production. Searches for alternative sources and production complexity found no passage addressing that comparison; page numbers were unavailable in our copy. (LLM, conf=0.74)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    PDRN has demonstrated a strong safety profile in both acute and chronic toxicity studies, with no significant immunogenic responses.

    “PDRN has demonstrated a strong safety profile in both acute and chronic toxicity studies, where no significant immunogenic responses were observed [11,17,19].”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [11] Marques, C., Porcello, A., Cerrano, M., Hadjab, F., Chemali, M., Lourenço, K., Hadjab, B., Raffoul, W., Applegate, L.A., and Laurent, A.E. (2025). From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules. Biomolecules, 15. source

      Section 4 (page not available) reports that salmon-derived PDRN/PN has a lower chance of eliciting an immune response and cites studies of its biocompatibility and safety. The paper does not report acute or chronic toxicity-study results or state that those studies observed no significant immunogenic responses. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [17] Khan, 2022, Polydeoxyribonucleotide: A promising skin anti-aging agent, Chin. J. Plast. Reconstr. Surg. source

      The “Safety of use” passage reports no toxicity after repeated systemic administration in mice and rats and attributes an absence of immunological effects to PDRN’s purification process. It supports a favorable safety profile, but does not describe both acute and chronic toxicity studies or report measured immunogenic responses in those studies. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [19] Squadrito, 2017, Pharmacological Activity and Clinical Use of PDRN, Front. Pharmacol. source

      The Safety section reports no organ toxicity or mortality in acute and chronic studies in mice and rats, and describes PDRN’s overall safety profile as excellent. The Discussion says a lack of effects on the immune system contributes to that profile, but the paper does not report that the toxicity studies measured immunogenic responses or observed none. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Two primary extraction methods, chemical and non-organic, are used for isolating PDRN from salmon sources.

    “Two primary extraction methods, namely chemical and non-organic approaches, are used for isolating PDRN from salmon sources.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [159] DeCollibus, 2023, Considerations for the Terminal Sterilization of Oligonucleotide Drug Products, Nucleic Acid Ther. source

      The Extractables and leachables section discusses chemicals extracted from drug-product packaging, not isolation of PDRN from salmon. Searches for PDRN, salmon, and chemical versus non-organic extraction found no passage addressing the claimed methods; the paper’s Preamble identifies its subject as terminal sterilization of oligonucleotide drug products. Page numbers were not available in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [160] Yi, 2023, A Review on “Skin Boosters”: Hyaluronic Acid, Poly-L-lactic Acid and Pol-D-lactic Acid, Polydeoxyribonucleotide, Polynucleotides, Growth Factor, and Exosome, Korean Assoc. Laser Dernatology Trichology source

      The Deoxyribonucleic Fragments section discusses PDRN and DNA fragments in wound healing and cosmetic use, but does not describe how PDRN is isolated. Searches for chemical and non-organic extraction approaches and salmon sources found no supporting passage in our copy; the extraction methods mentioned in the Exosome section concern exosomes, not PDRN. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
    • cites [161] Rho, 2024, Injectable “Skin Boosters” in Aging Skin Rejuvenation: A Current Overview, Arch. Plast. Surg. source

      The Natural Biopolymers > Polynucleotide section (page unavailable) says PDRN is primarily derived from salmon trout or chum salmon sperm DNA. It does not describe two extraction methods or identify chemical and non-organic approaches; searches for those terms and for PDRN isolation found no such passage. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The chemical method for isolating PDRN involves multiple steps including thawing, cell lysis, sterilization, molecular weight reduction, precipitation, and granulation.

    “it involves multiple steps including thawing, cell lysis, sterilization, molecular weight reduction, precipitation, and granulation”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [159] DeCollibus, 2023, Considerations for the Terminal Sterilization of Oligonucleotide Drug Products, Nucleic Acid Ther. source

      The Introduction’s “Sterile drug product manufacturing” section describes oligonucleotide formulation, membrane filtration, and aseptic filling, not chemical isolation of PDRN. Searches for PDRN, thawing, cell lysis, molecular-weight reduction, precipitation, and granulation found no passage describing the claimed sequence of steps. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [160] Yi, 2023, A Review on “Skin Boosters”: Hyaluronic Acid, Poly-L-lactic Acid and Pol-D-lactic Acid, Polydeoxyribonucleotide, Polynucleotides, Growth Factor, and Exosome, Korean Assoc. Laser Dernatology Trichology source

      The paper’s “Deoxyribonucleic Fragments (PDRN; PN)” section discusses uses and effects of DNA fragments, but not how PDRN is chemically isolated. Searches for the listed steps and for PDRN extraction and purification found no passage describing thawing, cell lysis, sterilization, molecular-weight reduction, precipitation, or granulation. Page numbers were not available in our copy. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
    • cites [161] Rho, 2024, Injectable “Skin Boosters” in Aging Skin Rejuvenation: A Current Overview, Arch. Plast. Surg. source

      The Polynucleotide section describes PDRN’s source, purity, properties, and uses, but not a chemical isolation procedure. Searches for the listed steps and for PDRN extraction or purification found no passage addressing those steps. (LLM, conf=0.74)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    PDRN's effects are primarily mediated through upregulation of VEGF and IL-10, and downregulation of TNF-α, IL-6, HMGB1, and IL-1β.

    “These effects are primarily mediated through upregulation of vascular endothelial growth factor (VEGF) and interleukin (IL)-10, and downregulation of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), IL-6, high mobility group box-1 (HMGB1), and IL-1β [71,72].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [71] Colangelo, 2020, The Effects of Polydeoxyribonucleotide on Wound Healing and Tissue Regeneration: A Systematic Review of the Literature, Regen. Med. source
    • cites [72] Kim, D.-S., Lee, J.-K., Jung, J.-W., Baek, S.-W., Kim, J.H., Heo, Y., Kim, T.-H., and Han, D.K. (2021). Promotion of Bone Regeneration Using Bioinspired PLGA/MH/ECM Scaffold Combined with Bioactive PDRN. Materials, 14. source

      Section 3.4 (page not provided) reports increased VEGF expression and reduced IL-6 and IL-1β expression with the PDRN-containing scaffold. The paper does not report the claimed changes in IL-10, TNF-α, or HMGB1, and sections 1 and 3.3 describe A2A-receptor stimulation and the salvage pathway rather than establishing the listed factors as PDRN’s primary mediators. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In dermal fibroblasts, PDRN enhances metabolic activity and promotes the synthesis of collagen types I and III through activation of the ERK pathway.

    “In dermal fibroblasts, PDRN enhances metabolic activity and promotes the synthesis of essential ECM components—particularly collagen types I and III—through activation of the extracellular signal-regulated kinase (ERK) pathway [52,89,90,91,92,93,94].”
    Quote in the paperSubstantial claim2 of 7 sources checked
    • cites [52] Thellung, 1999, Polydeoxyribonucleotides enhance the proliferation of human skin fibroblasts: Involvement of A2 purinergic receptor subtypes, Life Sci. source
    • cites [89] Tharaux, 2000, Angiotensin II Activates Collagen I Gene Through a Mechanism Involving the MAP/ER Kinase Pathway, Hypertension source
    • cites [90] Belletti, 2007, Polydeoxyribonucleotide promotes cyclobutane pyrimidine dimer repair in UVB-exposed dermal fibroblasts, Photodermatol. Photoimmunol. Photomed. source

      The Results (p53 levels; page unavailable) and Discussion (page unavailable) report that PDRN increased p53 expression and accelerated repair of UVB-induced DNA damage in dermal fibroblasts. Searches for metabolic activity, collagen types I and III, and ERK found no passage addressing those claimed effects or mechanism. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [91] Ishii, 2000, Collagen and elastin degradation by matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase in aortic dissection, Hum. Pathol. source
    • cites [92] Fourtanier, 2000, Age dependent increase of elastase type protease activity in mouse skin, J. Photochem. Photobiol. B Biol. source
    • cites [93] Kim, H.M., Byun, K.-A., Oh, S., Yang, J.Y., Park, H.J., Chung, M.S., Son, K.H., and Byun, K. (2022). A Mixture of Topical Forms of Polydeoxyribonucleotide, Vitamin C, and Niacinamide Attenuated Skin Pigmentation and Increased Skin Elasticity by Modulating Nuclear Factor Erythroid 2-like 2. Molecules, 27. source

      The Introduction (page unavailable) reports that PDRN enhances fibroblast metabolism and synthesis of dermal matrix components. The Discussion (page unavailable) reports increased collagen type I staining in PDRN-treated animal skin, but it does not establish synthesis of collagen types I and III in dermal fibroblasts. The passages found do not link these effects to ERK activation. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [94] Park, 2025, Effects of Chlorella protothecoides-derived polydeoxyribonucleotides on skin regeneration and wound healing, Arch. Dermatol. Res. source

  • May combine two claims.

    Premisecitation

    Upon enzymatic degradation, PDRN yields a pool of bioavailable nucleosides and nucleotides that can be rapidly reincorporated into cellular processes, promoting tissue regeneration and accelerating wound healing.

    “Upon enzymatic degradation, PDRN yields a pool of bioavailable nucleosides and nucleotides that can be rapidly reincorporated into cellular processes, thereby promoting tissue regeneration and accelerating wound healing [50,75,76,77].”
    Quote in the paperSubstantial claim3 of 4 sources checked
    • cites [50] Shin, 2020, Polydeoxyribonucleotide-delivering therapeutic hydrogel for diabetic wound healing, Sci. Rep. source

      The Introduction says PDRN is degraded by DNA nuclease and links its wound-healing effects to A2A receptors and salvage pathways. The Abstract reports accelerated diabetic wound healing with a PDRN-loaded hydrogel. Neither passage states that degradation yields a bioavailable pool of nucleosides and nucleotides that is rapidly reincorporated into cellular processes, so the claim’s specific mechanism is not supported. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [75] Jeong, W., Yang, C.E., Roh, T.S., Kim, J.H., Lee, J.H., and Lee, W.J. (2017). Scar Prevention and Enhanced Wound Healing Induced by Polydeoxyribonucleotide in a Rat Incisional Wound-Healing Model. Int. J. Mol. Sci., 18. source

      The Discussion (page not provided) reports faster wound healing after PDRN treatment and attributes it to reduced inflammation and increased collagen synthesis. The Introduction describes PDRN as a mixture of nucleotides, but our copy does not say that enzymatic degradation releases bioavailable nucleosides and nucleotides for rapid reincorporation into cellular processes. That proposed mechanism is not supported by this source. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [76] Bitto, 2008, Polydeoxyribonucleotide improves angiogenesis and wound healing in experimental thermal injury, Crit. Care Med. source
    • cites [77] Hwang, 2018, An effective range of polydeoxyribonucleotides is critical for wound healing quality, Mol. Med. Rep. source

      The Introduction says PDRN products may contain deoxynucleosides and deoxynucleotides, and the Discussion reports improved wound-regeneration quality with PDRN. Neither passage says these components arise through enzymatic degradation or are rapidly reincorporated into cellular processes; the paper instead links its observed healing effect to cell migration. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    A2A receptor activation by PDRN reduces inflammatory cell infiltration, promotes proliferation and migration of reparative cells, stimulates VEGF production, and facilitates fibroblast differentiation and maturation.

    “A2A receptor activation by PDRN reduces inflammatory cell infiltration, promotes proliferation and migration of reparative cells, stimulates vascular endothelial growth factor (VEGF) production, and facilitates fibroblast differentiation and maturation, thereby accelerating the reparative cascade [112,113].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [112] Kwon, 2019, Polydeoxyribonucleotides Improve Diabetic Wound Healing in Mouse Animal Model for Experimental Validation, Ann. Dermatol. source

      The Discussion (page not supplied) links PDRN to A2A-receptor stimulation and increased VEGF expression; the Results report increased fibroblast proliferation. The paper does not report reduced inflammatory-cell infiltration or fibroblast differentiation and maturation, and its observed increase in fibroblast migration was not statistically significant. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [113] Baek, 2018, Effect of Polydeoxyribonucleotide on Angiogenesis and Wound Healing in an In Vitro Model of Osteoarthritis, Cell Transplant. source

      The Introduction describes PDRN as activating the A2A receptor and enhancing cell proliferation in experimental healing models. The Results report increased VEGF expression and migration of chondrocytic cells after PDRN treatment in an in vitro osteoarthritis model. The paper does not establish reduced inflammatory-cell infiltration or fibroblast differentiation and maturation, and its migration findings do not cover reparative cells generally. (LLM, conf=0.89)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The chemical method for isolating PDRN from salmon is cost-effective and technically accessible.

    “While the chemical method is cost-effective and technically accessible”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [159] DeCollibus, 2023, Considerations for the Terminal Sterilization of Oligonucleotide Drug Products, Nucleic Acid Ther. source

      The Introduction and Problem Statement discuss oligonucleotide formulations and terminal sterilization, not isolation of PDRN from salmon. Searches for PDRN, salmon extraction, and the chemical method found no passage addressing its cost or technical accessibility. The available passages provide no basis to verify the claim. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [160] Yi, 2023, A Review on “Skin Boosters”: Hyaluronic Acid, Poly-L-lactic Acid and Pol-D-lactic Acid, Polydeoxyribonucleotide, Polynucleotides, Growth Factor, and Exosome, Korean Assoc. Laser Dernatology Trichology source

      The Deoxyribonucleic Fragments section discusses PDRN and PN in skin care but does not describe isolating PDRN from salmon. Searches for chemical isolation, cost, and technical accessibility found no passage addressing those claims; the cost discussion in the Exosome section concerns exosomes instead. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
    • cites [161] Rho, 2024, Injectable “Skin Boosters” in Aging Skin Rejuvenation: A Current Overview, Arch. Plast. Surg. source

      The Polynucleotide section says PDRN is derived from salmon sperm DNA but does not describe a chemical isolation method or assess its cost or technical accessibility. The Delivery Methods section calls conventional intradermal injections cost-effective; that is a different procedure. Searches for chemical isolation, extraction, and production did not find support for the attributed claim. (LLM, conf=0.74)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Alternative biological sources such as plants, algae, and sea cucumbers have been explored for PDRN production.

    “Alternative approaches using biological sources such as plants, algae, and sea cucumbers have also been explored for PDRN production”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [134] Shu, Z., Ji, Y., Liu, F., Jing, Y., Jiao, C., Li, Y., Zhao, Y., Wang, G., and Zhang, J. (2024). Proteomics Analysis of the Protective Effect of Polydeoxyribonucleotide Extracted from Sea Cucumber (Apostichopus japonicus) Sperm in a Hydrogen Peroxide-Induced RAW264.7 Cell Injury Model. Mar. Drugs, 22. source

      The Discussion and Methods §4.2 describe extracting PDRN from sea cucumber sperm, supporting that example of an alternative source. The paper does not report exploring plants or algae for PDRN production; the plant material mentioned in the Results is a different antioxidant, not a PDRN source. Page numbers were not available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [163] Cheng, 2016, An update review on recent skin fillers, Plast. Aesthetic Res. source

      The review’s Platelet-rich plasma and Human-derived bioengineered collagen implants sections discuss other materials, not PDRN production. Searches for PDRN, polydeoxyribonucleotide, and plants, algae, or sea cucumbers found no passage addressing the claimed sources; page numbers were unavailable in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [164] Cavallini, 2020, Consensus report on the use of PN-HPT™ (polynucleotides highly purified technology) in aesthetic medicine, J. Cosmet. Dermatol. source

      The Background (page unavailable) describes the polynucleotides in this report as DNA extracted from trout gonads. Neither that passage nor the additional passages found by searching for plants, algae, sea cucumbers, and alternative biological sources addresses whether those sources have been explored for PDRN production. (LLM, conf=0.75)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    PDRN inhibits elastase and MMP-1, preserving elastin integrity, improving skin elasticity, and reducing wrinkle depth.

    “Concurrently, it inhibits elastase and matrix metalloproteinase-1 (MMP-1), which are enzymes responsible for ECM degradation, preserving elastin integrity, improving skin elasticity, and reducing wrinkle depth [91,92,93].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [91] Ishii, 2000, Collagen and elastin degradation by matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase in aortic dissection, Hum. Pathol. source
    • cites [92] Fourtanier, 2000, Age dependent increase of elastase type protease activity in mouse skin, J. Photochem. Photobiol. B Biol. source
    • cites [93] Kim, H.M., Byun, K.-A., Oh, S., Yang, J.Y., Park, H.J., Chung, M.S., Son, K.H., and Byun, K. (2022). A Mixture of Topical Forms of Polydeoxyribonucleotide, Vitamin C, and Niacinamide Attenuated Skin Pigmentation and Increased Skin Elasticity by Modulating Nuclear Factor Erythroid 2-like 2. Molecules, 27. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Products from alternative biological source approaches for PDRN production are often safeguarded by patents.

    “and the products are often safeguarded by patents [134,163,164]”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [134] Shu, Z., Ji, Y., Liu, F., Jing, Y., Jiao, C., Li, Y., Zhao, Y., Wang, G., and Zhang, J. (2024). Proteomics Analysis of the Protective Effect of Polydeoxyribonucleotide Extracted from Sea Cucumber (Apostichopus japonicus) Sperm in a Hydrogen Peroxide-Induced RAW264.7 Cell Injury Model. Mar. Drugs, 22. source

      The Introduction and Discussion describe PDRN sources and extraction from sea cucumber sperm, but do not address patent protection. Searches for patents, proprietary products, and alternative-source production found no passage supporting the claim that such products are often patented. Page numbers were not available in our copy. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
    • cites [163] Cheng, 2016, An update review on recent skin fillers, Plast. Aesthetic Res. source

      The Platelet-rich plasma section discusses PRP preparation and cosmetic use, not PDRN production. Searches for PDRN, alternative biological sources, and patents found no passage addressing whether such products are patented; the paper’s full-text copy is not marked as truncated. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
    • cites [164] Cavallini, 2020, Consensus report on the use of PN-HPT™ (polynucleotides highly purified technology) in aesthetic medicine, J. Cosmet. Dermatol. source

      The Conflict of Interest section says Mastelli holds patents for PN-HPT™ and produces PN-HPT™-based medical devices. The Background identifies polynucleotides as extracted from trout gonads, but the paper does not establish that products from alternative biological sources are often patented. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    PN has shown favorable outcomes in improving knee function and alleviating pain without causing serious adverse effects.

    “In addition, PN has shown favorable outcomes in improving knee function and alleviating pain without causing serious adverse effects [42,43,44,45,46,47].”
    Quote in the paperNot a substantial claim5 of 6 sources checked
    • cites [42] Migliore, 2015, Effectiveness and utility of hyaluronic acid in osteoarthritis, Bone Abstr. source

      The Introduction reports improved knee pain and function and low rates of adverse effects for hyaluronic acid (HA), not PN. A search for PN and polynucleotide treatment found no passage in our copy addressing PN’s outcomes or safety. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [43] Kuppa, S.S., Kim, H.-K., Kang, J.-Y., Lee, S.-C., Yang, H.-Y., Sankaranarayanan, J., and Seon, J.-K. (2023). Polynucleotides Suppress Inflammation and Stimulate Matrix Synthesis in an In Vitro Cell-Based Osteoarthritis Model. Int. J. Mol. Sci., 24. source

      The Introduction (p. unavailable) reports that intra-articular PN reduces pain and improves function in patients with knee osteoarthritis. The Discussion (p. unavailable) describes minimal adverse effects and a low risk of adverse effects, but this in vitro study does not establish that patients experienced no serious adverse effects. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [44] Kim, 2023, A randomized controlled trial for comparing efficacy and safety between intraarticular polynucleotide and hyaluronic acid for knee osteoarthritis treatment, Sci. Rep. source
    • cites [45] Bowman, 2018, Recent advances in hyaluronic acid based therapy for osteoarthritis, Clin. Transl. Med. source

      The Introduction and Human clinical studies involving hyaluronic acid sections discuss pain relief, function, and adverse reactions for hyaluronic acid injections, not PN. A search for “polynucleotide” found no passage addressing PN’s effects on knee function, pain, or serious adverse effects. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [46] Moon, 2022, Comparison of Polynucleotide, Sodium Hyaluronate, and Crosslinked Sodium Hyaluronate for the Management of Painful Knee Osteoarthritis: A Multi-Center, Randomized, Double-Blind, Parallel-Group Study, Pain Med. source
    • cites [47] Lee, D., Kim, W.-H., Ha, J.H., Kim, H., Kim, J., and Shin, D.W. (2025). Current Practices and Perceived Effectiveness of Clinicians Regarding Polynucleotide Injection for Knee Osteoarthritis: A Survey-Based Evaluation. Healthcare, 13. source

      The Results (§3.3; page unavailable) report clinicians’ ratings of better pain relief and smoother joint movement with PN than with HA. The Discussion (§4; page unavailable) says these are perceived benefits, not measured improvements in knee function, and notes that complications can occur; it does not establish an absence of serious adverse effects. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    PNs have high biocompatibility and biodegradability, favorable safety profiles, and low immunogenicity, making them suitable as facial fillers.

    “Their high biocompatibility and biodegradability, accompanied by favorable safety profiles and low immunogenicity, also make them suitable as facial fillers [22,24,31,152,161,167].”
    Quote in the paperSubstantial claim3 of 6 sources checked
    • cites [22] Park, 2015, Long-chain polynucleotide filler for skin rejuvenation: Efficacy and complications in five patients, Dermatol. Ther. source

      The Discussion reports use of a PN filler for facial skin rejuvenation and concludes that it seems safe, based on five patients. It does not establish high biocompatibility, biodegradability, or low immunogenicity, or identify those properties as reasons PNs are suitable as facial fillers. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [24] Kim, M.J., Park, H., Jung, R., Won, C., Ohk, S., Kim, H., Roh, N., and Yi, K. (2024). High-resolution 3-D scanning electron microscopy (SEM) images of DOT™ polynucleotides (PN): Unique scaffold characteristics and potential applications in biomedicine. Ski. Res. Technol., 30. source

      The Discussion describes PN as highly biocompatible and reports facial volumization uses with no serious adverse events in the studies it summarizes. The Introduction also describes a favorable safety record. However, the Discussion presents biodegradation and negligible immune response as criteria for an ideal scaffold, not as demonstrated properties of PN; the claimed low immunogenicity and biodegradability are therefore unsupported by this copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [31] Kim, 2020, Comparison of the effects of polynucleotide and hyaluronic acid fillers on periocular rejuvenation: A randomized, double-blind, split-face trial, J. Dermatol. Treat.

      Not checked in the free run.

    • cites [152] (2025, June 23). Drug Approval by MFDS, Drug Information, Announcement of Drug Master File (DMF) Registration: Search by ingredient-Sodium polydeoxyribonucleotide, Available online: https://nedrug.mfds.go.kr/.

      Not checked in the free run.

    • cites [161] Rho, 2024, Injectable “Skin Boosters” in Aging Skin Rejuvenation: A Current Overview, Arch. Plast. Surg. source

      The Polynucleotide section (page unavailable) describes PN as a safe intradermal option for facial skin rejuvenation with a high immunological safety profile. It discusses PN filler studies, but does not state that PN has high biocompatibility or biodegradability; those properties are discussed elsewhere for other polymers. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [167] Nabila, I. (2024). Literature Review Mikroinjeksi Deoxyribonucleic Acid (DNA) Salmon Sebagai Agen Peremajaan Kulit Wajah. [Ph.D. Thesis, Universitas Muhammadiyah Surabaya].

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The commercialization of Placentex® catalyzed advancements in DNA purification technologies.

    “and catalyzed advancements in DNA purification technologies [147,148,168].”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [147] Nguyen, T.H., Wang, S.-L., and Nguyen, V.B. (2024). Recent advances on polydeoxyribonucleotide extraction and its novel application in cosmeceuticals. Int. J. Biol. Macromol., 282. source
    • cites [148] Rubegni, 2001, Clinical Evaluation of the Trophic Effect of Polydeoxyribonucleotide (PDRN) in Patients Undergoing Skin Explants. A Pilot Study, Curr. Med. Res. Opin. source
    • cites [168] Araco, 2022, Clinical efficacy and safety of polynucleotides highly purified technology (PN-HPT®) and cross-linked hyaluronic acid for moderate to severe nasolabial folds: A prospective, randomized, exploratory study, J. Cosmet. Dermatol. source

      The Discussion distinguishes PN-HPT® from PDRN and describes their clinical uses, but does not mention Placentex® or a history of DNA purification. Searches for Placentex® commercialization and advances in DNA purification found no passage addressing the claimed causal link. No page numbers are available in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Placentex® is manufactured using a proprietary High Purification Technology (HPT) designed to enhance purity and partially control the polymer length.

    “This product is manufactured using a proprietary High Purification Technology (HPT) designed to enhance purity and partially control the polymer length [165,166].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [165] Lee, 2018, Comparison of wound healing effects between Oncorhynchus keta-derived polydeoxyribonucleotide (PDRN) and Oncorhynchus mykiss-derived PDRN, Arch. Craniofacial Surg. source

      The Introduction (page unavailable) says PDRN medications are obtained by high-temperature extraction, have purity above 95%, and comprise polymers of 50–2,000 base pairs. The Methods—Materials section identifies Placentex as a PDRN injection. Neither section says Placentex is manufactured using proprietary High Purification Technology (HPT) or that its manufacturing process controls polymer length. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [166] Palmieri, 2023, An Innovative PN HPT™-based Medical Device for the Therapy of Deteriorated Periocular Skin Quality, Surg. Res. source

      The Introduction describes a patented purification process that produces a pure ingredient with polynucleotide fragments of 50–2,000 base pairs, supporting the purity and polymer-length portions of the claim. But the paper identifies the studied product as PLINEST eye (Abstract), not Placentex®, and does not establish that Placentex® is manufactured using this technology. Page numbers were not available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The commercialization of Placentex® in the early 1990s marked a significant milestone in the therapeutic use of PDRN.

    “The commercialization of Placentex® in the early 1990s marked a significant milestone in the therapeutic use of PDRN”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [147] Nguyen, T.H., Wang, S.-L., and Nguyen, V.B. (2024). Recent advances on polydeoxyribonucleotide extraction and its novel application in cosmeceuticals. Int. J. Biol. Macromol., 282. source
    • cites [148] Rubegni, 2001, Clinical Evaluation of the Trophic Effect of Polydeoxyribonucleotide (PDRN) in Patients Undergoing Skin Explants. A Pilot Study, Curr. Med. Res. Opin. source
    • cites [168] Araco, 2022, Clinical efficacy and safety of polynucleotides highly purified technology (PN-HPT®) and cross-linked hyaluronic acid for moderate to severe nasolabial folds: A prospective, randomized, exploratory study, J. Cosmet. Dermatol. source

      The Discussion distinguishes PDRN from PN‐HPT® and describes a current therapeutic indication for PDRN, but does not mention Placentex® or its commercialization. Searches for Placentex®, commercialization, and the early 1990s found no passage addressing the claimed milestone; no page numbers are available in our copy. (LLM, conf=0.77)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    DNA fragment Optimizing Technology (DOTTM), developed by PharmaResearch Co. Ltd., has been used in the production of both PN and PDRN formulations.

    “DNA fragment Optimizing Technology (DOT™), developed by PharmaResearch Co. Ltd., has been used in the production of both PN and PDRN formulations [24,169,170,171].”
    Quote in the paperNot a substantial claim3 of 4 sources checked
    • cites [24] Kim, M.J., Park, H., Jung, R., Won, C., Ohk, S., Kim, H., Roh, N., and Yi, K. (2024). High-resolution 3-D scanning electron microscopy (SEM) images of DOT™ polynucleotides (PN): Unique scaffold characteristics and potential applications in biomedicine. Ski. Res. Technol., 30. source

      The Introduction identifies DOT™ as proprietary technology used to produce PharmaResearch’s PN formulation, and the Introduction and Discussion also refer to DOT™ PDRN. The paper does not expand DOT™ as “DNA fragment Optimizing Technology” or explicitly say that PharmaResearch developed it; its link between the company and DOT™ PDRN is less direct. No page numbers are available in our copy. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [169] Kim, 2018, Preventive effect of polynucleotide on post-thyroidectomy scars: A randomized, double-blinded, controlled trial, Lasers Surg. Med. source
    • cites [170] Yogya, 2022, Efficacy and Safety of Using Noninsulated Microneedle Radiofrequency Alone versus in Combination with Polynucleotides for Treatment of Periorbital Wrinkles, Dermatol. Ther. source

      The Methods describe a PN serum identified as a Reanzen Co. product, and the Discussion describes PNs generally. Neither passage addresses DOT™, PharmaResearch, PDRN, or whether that technology is used to produce PN and PDRN formulations (searched those terms and DNA-fragment production). (LLM, conf=0.74)

      Experimental — accuracy not yet measured
    • cites [171] Hong, 2024, Therapeutic Performance of Needle Injection Versus Needle-Free Jet Injector System for Polynucleotide Filler in Skin Rejuvenation, J. Cosmet. Dermatol. source

      Materials and Methods > Devices (page unavailable) identifies a Pharmaresearch PN product, but does not describe how it was produced. Searches for DOT, DNA fragment Optimizing Technology, and PDRN found no passage saying the technology was developed by PharmaResearch or used to produce both PN and PDRN formulations. (LLM, conf=0.74)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    PDRNs are increasingly incorporated into cosmetic products for topical use and are registered as sodium DNA or hydrolyzed DNA.

    “Furthermore, PDRNs are also increasingly being incorporated into cosmetic products for topical use and are registered as sodium DNA or hydrolyzed DNA [135,175].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [135] Chae, D., Oh, S.-W., Choi, Y.-S., Kang, D.-J., Park, C.-W., Lee, J., and Seo, W.-S. (2025). First Report on Microbial-Derived Polydeoxyribonucleotide: A Sustainable and Enhanced Alternative to Salmon-Based Polydeoxyribonucleotide. Curr. Issues Mol. Biol., 47. source

      Section 2.4 states that INCI designates PDRN and L-PDRN as sodium DNA or hydrolyzed DNA. The Discussion identifies topical cosmetics as a potential application, but the paper does not establish that PDRNs are increasingly being incorporated into cosmetic products. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [175] (2025, July 23). Cosmetic Ingredient Dictionary by the Korean Cosmetic Association. Available online: https://kcia.or.kr/cid/search/ingd_view.php?no=1048.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PDRNs are classified as prescription medications approved for injectable use for wound healing/tissue repair and knee osteoarthritis.

    “PDRNs are classified as prescription medications approved for injectable use for wound healing/tissue repair and knee osteoarthritis [19,173,174].”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [19] Squadrito, 2017, Pharmacological Activity and Clinical Use of PDRN, Front. Pharmacol. source

      The Abstract calls PDRN a registered drug, and the Safety section reports dispensed prescriptions. The clinical-studies section describes injectable PDRN improving healing of diabetic foot ulcers. It does not establish approval for injectable treatment of wound healing or tissue repair, and its osteoarthritis example concerns a topical gel, not an approved knee injection (page numbers unavailable). (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [173] Kim, 2019, The efficacy and safety of polydeoxyribonucleotide for the treatment of knee osteoarthritis, Medicine source

      The Introduction and Discussion describe PDRN injections studied for knee osteoarthritis, and the Introduction notes earlier therapeutic use for skin conditions. Neither section establishes that PDRNs are classified as prescription medications or approved for injectable use for wound healing, tissue repair, or knee osteoarthritis. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [174] Jo, 2023, Therapeutic effects of polydeoxyribonucleotide in an in vitro neuronal model of ischemia/reperfusion injury, Sci. Rep. source

      The Results section describes PDRN as a drug used to treat osteoarthritis, and the References list studies of wound healing and intra-articular injections for knee osteoarthritis (no page numbers available). The paper does not say PDRNs are classified as prescription medications or approved for injectable use for either indication. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Although PN and PDRN have been extensively investigated, few studies have explored alternative sources, such as plant-, microbe-, and seaweed-derived nucleotides, underscoring a substantial gap in comprehensive characterization.

    “Although PN and PDRN have been extensively investigated, few studies explored alternative sources, such as plant-, microbe-, and seaweed-derived nucleotides, underscoring a substantial gap in comprehensive characterization [11,134,135,179,180,181].”
    Quote in the paperNot a substantial claim4 of 6 sources checked
    • cites [11] Marques, C., Porcello, A., Cerrano, M., Hadjab, F., Chemali, M., Lourenço, K., Hadjab, B., Raffoul, W., Applegate, L.A., and Laurent, A.E. (2025). From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules. Biomolecules, 15. source

      Section 4 (page unavailable) says salmon is the main source and identifies studies of plant- and red-alga-derived PDRN. It does not identify microbe-derived sources or establish that few studies examine alternatives or that their characterization has a substantial gap; it says their extraction and purification have been extensively reviewed. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [134] Shu, Z., Ji, Y., Liu, F., Jing, Y., Jiao, C., Li, Y., Zhao, Y., Wang, G., and Zhang, J. (2024). Proteomics Analysis of the Protective Effect of Polydeoxyribonucleotide Extracted from Sea Cucumber (Apostichopus japonicus) Sperm in a Hydrogen Peroxide-Induced RAW264.7 Cell Injury Model. Mar. Drugs, 22. source

      The Introduction says PDRN is primarily derived from human placenta, salmon sperm, and trout sperm. The Discussion reports the first extraction of PDRN from sea cucumber sperm and says research on active substances in sea cucumber viscera is limited. It does not address plant-, microbe-, or seaweed-derived nucleotides or establish a general gap in their comprehensive characterization. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [135] Chae, D., Oh, S.-W., Choi, Y.-S., Kang, D.-J., Park, C.-W., Lee, J., and Seo, W.-S. (2025). First Report on Microbial-Derived Polydeoxyribonucleotide: A Sustainable and Enhanced Alternative to Salmon-Based Polydeoxyribonucleotide. Curr. Issues Mol. Biol., 47. source

      The Introduction describes PDRN as predominantly salmon-derived and says research on microbial-derived PDRN is lacking. It also identifies studies of plant- and seaweed-derived PDRN, but does not establish that few studies have explored alternative sources overall or a general gap in their comprehensive characterization; it does not discuss PN separately. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [179] Kim, 2023, Efficacy in vitro Antioxidation and in vivo Skin Barrier Recovery of Composition Containing Mineral-cation-phyto DNA Extracted from Aloe vera Adventitious Root, Asian J. Beauty Cosmetol. source

      The Introduction (indexed under Abstract; page unavailable) describes the paper’s study of DNA extracted from Aloe vera roots, contrasts it with commonly studied salmon PDRN, and mentions seaweed-derived PDRN. It does not establish that few studies examine alternative sources, address microbe-derived nucleotides, or identify a substantial gap in comprehensive characterization. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [180] Song, 2022, Efficiency of PDNR (Polydeoxyribonucleotide) Extraction from Various Plant Species and Its in Vitro Wound Healing Activity, J. Korea Inst. Inf. Electron. Commun. Technol.

      Not checked in the free run.

    • cites [181] Yang, 2021, The effect of wound healing of Nile tilapia (Oreochromis niloticus) using PDRN (polydeoxyribonucleotide) extracted from seaweed (Porphyra sp.), J. Fish Pathol.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Clinical dosing regimens for PDRN vary depending on indication, with low-dose/low-level protocols often used for cosmetic and esthetic purposes and high-dose/high-level protocols reserved for regenerative therapies and wound repair.

    “Clinical dosing regimens vary depending on the indication, and low-dose/low-level protocols are often used for cosmetic and esthetic purposes, where high-dose/high-level protocols are reserved for regenerative therapies and wound repair [19,144,176,177].”
    Quote in the paperNot a substantial claim1 of 4 sources checked
    • cites [19] Squadrito, 2017, Pharmacological Activity and Clinical Use of PDRN, Front. Pharmacol. source

      The clinical-studies section (page unavailable) reports different PDRN administration routes and schedules for different indications, including skin-graft donor sites and diabetic foot ulcers. It does not describe low-dose protocols as common for cosmetic use or high-dose protocols as reserved for regeneration and wound repair; both cited wound-healing treatments use 5.625 mg per administration. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [144] Kim, 2015, Effectiveness of polydeoxyribonucleotide injection versus normal saline injection for treatment of chronic plantar fasciitis: A prospective randomised clinical trial, Int. Orthop. source
    • cites [176] Kim, 2023, Early Postoperative Injections of Polydeoxyribonucleotide Prevent Hypertrophic Scarring After Thyroidectomy: A Randomized Controlled Trial, Adv. Wound Care source
    • cites [177] Kim, 2022, Effects of Polynucleotide Dermal Filler in the Correction of Crow’s Feet Using an Antera Three-Dimensional Camera, Aesthetic Plast. Surg. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Placentex® is a PDRN-based therapeutic developed by Mastelli S.R.L. in Italy.

    “A notable example is Placentex®, a PDRN-based therapeutic developed by Mastelli S.R.L. in Italy.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [165] Lee, 2018, Comparison of wound healing effects between Oncorhynchus keta-derived polydeoxyribonucleotide (PDRN) and Oncorhynchus mykiss-derived PDRN, Arch. Craniofacial Surg. source
    • cites [166] Palmieri, 2023, An Innovative PN HPT™-based Medical Device for the Therapy of Deteriorated Periocular Skin Quality, Surg. Res. source

      The Acknowledgements (page unavailable) say that Mastelli S.r.l. in Italy developed the PN HPT™ technology and the injectable periocular gel tested in this study. The Methods identify that product as PLINEST eye, not Placentex®. Our copy does not identify Placentex® or describe it as PDRN-based, so the claim about that specific therapeutic is unsupported. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisenone given

    PN and PDRN differ significantly in molecular chain length distribution, structural characteristics, and clinical applications.

    “However, PN and PDRN differ significantly in molecular chain length distribution, structural characteristics, and clinical applications.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    PN plays a key role in extracellular matrix remodeling.

    “PN, composed of longer DNA fragments, plays a key role in extracellular matrix remodeling.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Relevant literature was identified via searches of PubMed, Google, Google Scholar, and Web of Science, including English-language publications up to May 2025.

    “Relevant literature was identified via searches of PubMed, Google, Google Scholar, and Web of Science, including English-language publications up to May 2025.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    PDRN is a DNA-based therapeutic agent characterized by a relatively lower molecular weight than conventional PN.

    “PDRN is a DNA-based therapeutic agent characterized by a relatively lower molecular weight than that of conventional PN.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    PDRN is primarily recognized for its pharmacological activity, acting through defined molecular pathways such as anti-inflammatory modulation and tissue regeneration.

    “PNs are generally associated with higher molecular weight and greater viscosity relative to PDRN, which is primarily recognized for its pharmacological activity, acting through defined molecular pathways such as anti-inflammatory modulation and tissue regeneration.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    PDRN contributes to the restoration of ECM homeostasis, the repair of dermal architecture, and sustained skin rejuvenation.

    “Through these concerted actions, PDRN contributes to the restoration of ECM homeostasis, the repair of dermal architecture, and sustained skin rejuvenation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    PN may function primarily as a structural and rheological support agent, whereas PDRN is more consistently characterized as a pharmacologically active molecule with well-defined mechanisms of action.

    “Based on current evidence, PN may function primarily as a structural and rheological support agent, whereas PDRN is more consistently characterized as a pharmacologically active molecule with well-defined mechanisms of action.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    PN-HA treatments are well-tolerated and effective for repairing the skin barrier.

    “PN-HA treatments are well-tolerated and effective for repairing the skin barrier [33,35,41].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [33] Titcomb, 2025, A literature review on polynucleotide efficacy on skin rejuvenation, and review of the regulatory status and guidelines around polynucleotides, J. Aesthetic Nurs. source
    • cites [35] Heo, 2025, Polynucleotide and Hyaluronic Acid Mixture for Skin Wound Dressing for Accelerated Wound Healing, Tissue Eng. Regen. Med. source
    • cites [41] Draelos, 2012, New treatments for restoring impaired epidermal barrier permeability: Skin barrier repair creams, Clin. Dermatol. source

  • May combine two claims.

    Premisecitation

    A2A receptor activation suppresses NF-κB and MAPK cascades, inhibiting proinflammatory responses and enhancing anti-inflammatory mechanisms.

    “A2A receptor activation suppresses intracellular signaling pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) cascades, which inhibits proinflammatory responses and enhances anti-inflammatory mechanisms [69].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [69] Persson, 2010, Effects of Adenosine A2A and A2B Receptor Activation on Signaling Pathways and Cytokine Production in Human Uroepithelial Cells, Pharmacology source

  • May combine two claims.

    Premisecitation

    PDRN downregulates MMP-1, initiating the collagen synthesis cascade and enhancing collagen production in dermal fibroblasts.

    “In addition, PDRN downregulates matrix metalloproteinase-1 (MMP-1), initiating the collagen synthesis cascade and enhancing collagen production in dermal fibroblasts [70].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [70] Bitto, 2011, Polydeoxyribonucleotide reduces cytokine production and the severity of collagen-induced arthritis by stimulation of adenosine A2A receptor, Arthritis Rheum. source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The scope of applications of nucleic acid polymers is expanding, particularly in Italy, South Korea, and other Asian countries.

    “The scope of their applications is expanding, particularly in Italy, South Korea, and other Asian countries.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Current research on PDRN and PN is largely concentrated in a limited number of countries, where regulatory frameworks and approval pathways differ.

    “Furthermore, current research on PDRN and PN is largely concentrated in a limited number of countries, where regulatory frameworks and approval pathways differ.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    These PDRN products are widely prescribed and administered for various skin health indications, highlighting the established role of PDRN in both medical dermatology and esthetic skin care.

    “These products are widely prescribed and administered for various skin health indications, highlighting the established role of PDRN in both medical dermatology and esthetic skin care.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Accumulating biological and clinical data indicates that both PDRN and PN can improve the condition of the skin and promote its regeneration, thereby mitigating visible signs of skin aging.

    “Accumulating biological and clinical data indicates that both PDRN and PN can improve the condition of the skin and promote its regeneration, thereby mitigating visible signs of skin aging.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Clinical improvements attributed to PDRN or PN in the cited studies are due to the nucleic acid component rather than other formulation components, concomitant procedures, or placebo effects.
    • Rests on an assumption: The outcome measures used in the cited studies, such as GAIS, CFGS, standardized photography, and 3D image analysis, validly reflect improvement in skin aging.

  • May combine two claims.

    Premisereasoning

    Clinically, PNs have been used to treat various facial areas, including marionette lines and the lips, providing long-lasting effects with a reduced risk of adverse events.

    “Clinically, PNs have been used to treat various facial areas, including marionette lines and the lips, providing long-lasting effects with a reduced risk of adverse events.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The same active compounds may be classified differently across countries.

    “As previously noted, the same active compounds may be classified differently across countries.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The effectiveness of PDRN and PN is highly dependent on formulation quality and appropriate clinical use.

    “Their effectiveness is highly dependent on formulation quality and appropriate clinical use”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Clinical improvements attributed to PDRN or PN in the cited studies are due to the nucleic acid component rather than other formulation components, concomitant procedures, or placebo effects.

  • May combine two claims.

    Premisecitation

    Multiple PDRN-based injectable products have received regulatory approval in South Korea and are actively used in dermatological clinics.

    “Multiple PDRN-based injectable products have received regulatory approval in South Korea and are actively used in dermatological clinics.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [178] (2025, June 19). Korea Pharmaceutical Information Center (KPIC): Drug Information Search—PDRN. Available online: https://www.health.kr/.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisereasoning

    Proprietary polynucleotide extraction and purification technologies are essential for quality assurance and have also been leveraged for branding and marketing purposes.

    “These technologies are not only essential for quality assurance but have also been leveraged for branding and marketing purposes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    These disparities hinder cross-national comparisons and complicate the generalization of clinical outcomes.

    “These disparities hinder cross-national comparisons and complicate the generalization of clinical outcomes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Numerous studies have used the terms PN and PDRN interchangeably, despite substantial differences in their molecular weight distributions and origins.

    “Notably, numerous studies have used the terms PN and PDRN interchangeably, despite substantial differences in their molecular weight distributions and origins.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Collectively, the findings indicate that PNs are potentially useful in managing key clinical signs of skin aging and have multifaceted utility in both esthetic and dermatologic applications.

    “Collectively, these findings underscore the potential usefulness of PNs in managing key clinical signs of skin aging and highlight their multifaceted utility in both esthetic and dermatologic applications.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Clinical improvements attributed to PDRN or PN in the cited studies are due to the nucleic acid component rather than other formulation components, concomitant procedures, or placebo effects.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Proprietary technologies such as Mastelli's HPTTM and PharmaResearch's DOTTM have been introduced, yet detailed methodologies remain largely undisclosed.

    “For instance, proprietary technologies such as Mastelli’s HPT™ and PharmaResearch’s DOT™ have been introduced, yet detailed methodologies remain largely undisclosed.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Premisenone given

    There is a broad consensus on the need to develop PDRN and PN from alternative sources to overcome limitations related to seasonal availability, high production costs, and environmental sustainability.

    “There is a broad consensus on the need to develop PDRN and PN from alternative sources to overcome limitations related to seasonal availability, high production costs, and environmental sustainability.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Nucleic acid polymers have been widely used to enhance skin health and are being incorporated into pharmaceuticals, medical devices, and cosmetic products, contingent upon varying regional regulatory classifications.

    “Nucleic acid polymers have been widely used to enhance skin health and have attracted increasing attention in research and are being incorporated into pharmaceuticals, medical devices, and cosmetic products, contingent upon varying regional regulatory classifications.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisereasoning

    To date, salmon- and trout-derived PDRN and PN continue to dominate dermatological applications, while research into alternative sources is ongoing.

    “To date, salmon- and trout-derived PDRN and PN continue to dominate dermatological applications, while research into alternative sources is ongoing.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Fine control of product molecular weight with HPT is challenging, often resulting in heterogeneity among DNA fragments.

    “fine control of product molecular weight is challenging, which often results in heterogeneity among DNA fragments [167].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [167] Nabila, I. (2024). Literature Review Mikroinjeksi Deoxyribonucleic Acid (DNA) Salmon Sebagai Agen Peremajaan Kulit Wajah. [Ph.D. Thesis, Universitas Muhammadiyah Surabaya].

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Despite differences in their molecular mechanisms and biological effects, both PDRN and PN hold substantial potential for extensive future research and development for dermatological applications.

    “Despite differences in their molecular mechanisms and biological effects, both compounds hold substantial potential for extensive future research and development for dermatological applications.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Clinical improvements attributed to PDRN or PN in the cited studies are due to the nucleic acid component rather than other formulation components, concomitant procedures, or placebo effects.

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    This compositional heterogeneity complicates direct comparisons across studies and underscores an urgent need for standardized definitions and characterization criteria within both research and clinical contexts.

    “This compositional heterogeneity complicates direct comparisons across studies and underscores an urgent need for standardized definitions and characterization criteria within both research and clinical contexts.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The interchangeable use of PN and PDRN in the literature, their broad molecular-weight ranges and distributions, and the varying purification methods were limitations encountered in conducting this review.

    “Nonetheless, several limitations were encountered in conducting this review. These included the interchangeable use of PN and PDRN in the literature, their broad molecular-weight ranges and distributions, and the varying purification methods.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Efforts to develop PDRN and PN from alternative sources are in their early stages.

    “However, these efforts are in their early stages.”
    Quote in the paperNot a substantial claim
61 of 61

  • The paper relies on this without support.

    The distinct characteristics of PDRN and PN are substantially underrecognized, resulting in clinical misapplications and suboptimal treatment outcomes.

    “However, the distinct characteristics of PDRN and PN are substantially underrecognized, resulting in clinical misapplications and suboptimal treatment outcomes.”

  • The paper relies on this without support.

    Distinctions between PN and PDRN are often defined solely by manufacturers, based on proprietary technologies and production methods.

    “Furthermore, these distinctions are often defined solely by manufacturers, based on proprietary technologies and production methods.”

  • The paper relies on this without support.

    The term PN is used inconsistently in both scientific literature and commercial labeling, frequently encompassing PDRN without clear differentiation.

    “The term of PN is also used inconsistently in both scientific literature and commercial labeling, frequently encompassing PDRN without clear differentiation.”

  • The paper relies on this without support.

    In some cases, formulations initially labeled as PN have subsequently been found to contain, or consist predominantly of, PDRN upon further analysis.

    “In some cases, formulations initially labeled as PN have subsequently been found to contain, or consist predominantly of, PDRN upon further analysis.”

  • The paper relies on this without support.

    Clinical improvements attributed to PDRN or PN in the cited studies are due to the nucleic acid component rather than other formulation components, concomitant procedures, or placebo effects.

    “Accumulating biological and clinical data indicates that both PDRN and PN can improve the condition of the skin and promote its regeneration, thereby mitigating visible signs of skin aging.”

  • The paper relies on this without support.

    The outcome measures used in the cited studies, such as GAIS, CFGS, standardized photography, and 3D image analysis, validly reflect improvement in skin aging.

    “Rejuran®, a commercially available purified PN, has shown efficacy in treating crow’s feet, with improvements substantiated by objective measurements such as the crow’s feet grading scale (CFGS), GAIS, standardized photography, and 3D image analysis [170].”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Contemporary literature suggests that PDRN-mediated activation of adenosine-dependent signaling pathways may contribute significantly to angiogenesis and tissue regeneration, whereas PN formulations may exert greater influence on dermal biostimulation and extracellular matrix remodeling.

    “Contemporary literature suggests that PDRN-mediated activation of adenosine-dependent signaling pathways may contribute significantly to angiogenesis and tissue regeneration, whereas PN formulations may exert greater influence on dermal biostimulation and extracellular matrix remodeling [5,18].”

    From Polynucleotides and Polydeoxyribonucleotides for Skin Rejuvenation, Postoperative Scar Prevention, and Wound Healing: A Systematic Review of Randomized Clinical Trials (2026) · cites this paper as [5]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Thailand claim cites an Australian regulatory listing

    Minor

    The text cites reference [157] for use of PN in Thailand, but [157] is a listing from Australia's Therapeutic Goods Administration. The citation does not match the country it is attached to.

  • PN-versus-HA filler trial is assigned a different study

    Minor

    The passage cites [170] for a PN-versus-HA filler trial. Reference [170] instead describes a comparison of microneedle radiofrequency alone versus radiofrequency combined with PN.

2 of 2

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1111/srt.13627

    Info

    The cited work was retracted on 2025-11-21 (notice 10.1111/srt.70297), not before this paper was published (2025-08-07).

    Cited work 10.1111/srt.13627 · retracted 2025-11-21 · notice 10.1111/srt.70297 · this paper published 2025-08-07

  • Cites a retracted work: 10.1111/jocd.16576

    Info

    The cited work was retracted on 2026-03-16 (notice 10.1111/jocd.70794), not before this paper was published (2025-08-07).

    Cited work 10.1111/jocd.16576 · retracted 2026-03-16 · notice 10.1111/jocd.70794 · this paper published 2025-08-07

2 of 2

Cites

2 retracted

Flagged first, then by citations

Research works printed but not linked: 3

  1. Nabila, I. (2024). Literature Review Mikroinjeksi Deoxyribonucleic Acid (DNA) Salmon Sebagai Agen Peremajaan Kulit Wajah. [Ph.D. Thesis, Universitas Muhammadiyah Surabaya].
  2. Song, 2022, Efficiency of PDNR (Polydeoxyribonucleotide) Extraction from Various Plant Species and Its in Vitro Wound Healing Activity, J. Korea Inst. Inf. Electron. Commun. Technol., 15, 387
  3. Yang, 2021, The effect of wound healing of Nile tilapia (Oreochromis niloticus) using PDRN (polydeoxyribonucleotide) extracted from seaweed (Porphyra sp.), J. Fish Pathol., 34, 233

Cited by

Sorted by citations

Related

Authors
Kim, S. T.
Affiliations
Inje University (KR)
Corresponding author
Kim, Sung Tae
ORCID
Kim, Sung Tae
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2025-08-07
Volume
17
Issue
8
Pages
1024
ISSN
1999-4923 (ISSN-L)
DOI
10.3390/pharmaceutics17081024
PMC
PMC12388916
OpenAlex
W4413037425
Cited by
18
References
172
Citations by year
2026: 17 · 2025: 1
FWCI
2.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmaceutics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Inje University
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Health Sciences › Medicine › Dermatology › Facial Rejuvenation and Surgery Techniques
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
Keywords
polynucleotides, polydeoxyribonucleotide, extracellular matrix remodeling, nucleotide salvage pathway, de novo nucleotide synthesis, skin rejuvenation, regenerative medicine, oligonucleotides

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-31.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-31.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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