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

Open access
Alhussain, Ahmed M, Turki M. Albusayys, Sarah, Alfhadi, Mohammed A, Bu Mozah, Saleh A, AlShammari, Shahad Saad S, Alanazi, Husam Abdullah M, Adil Alqazanli, Sara, Nouruldeen Alabdullah, Ali +3 more·2026·Cureus
DOI 10.7759/cureus.112403PMC PMC13453133
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Abstract

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

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review of seven randomized trials (183 participants) found PN- and PDRN-based therapies improved skin rejuvenation, postoperative scar quality, and wound healing, with the most consistent benefits in wound repair. Evidence remains limited by small samples, heterogeneous protocols, and variable outcomes.

Key findings

  • Across 7 RCTs, 4 evaluated skin rejuvenation, 1 postoperative scar prevention, and 2 wound healing; no serious treatment-related adverse events were reported.
  • Wound healing showed the strongest effects: in pressure ulcers, PDRN reduced median wound area at week 4 to 0.90 cm² vs 4.25 cm² with standard care (p<0.001) and improved PUSH scores to 4 vs 11 (p<0.001); in skin-graft donor sites, PDRN achieved 98.5% vs 53.5% re-epithelialization at day 15 (p<0.01), complete healing at 12.5 vs 24.45 days, and 0 vs 9 infections (45% control infection rate).
  • Postoperative scar prevention after thyroidectomy: PN reduced mean Vancouver Scar Scale scores from 6.05±0.52 to 2.09±0.47 at 16 weeks vs 6.25±0.59 to 4.01±0.55 in controls (p<0.05).
  • Aesthetic rejuvenation benefits were more modest but favorable: PDRN plus microneedling reduced mean Lemperle scores from 2.33±0.49 to 1.00±0.43 vs 1.50±0.52 with PRP (p=0.021); needle-free PN delivery lowered pain VAS to 2.9±1.52 vs 5.4±1.42 (p=0.017); ionization-adjusted PN filler lowered pain VAS to 3.39±1.81 vs 5.04±2.19 (p<0.005).

Methods

  • Systematic review conducted per PRISMA 2020 and prospectively registered in PROSPERO (CRD420261418096); PubMed, Embase, and CENTRAL were searched through January 2026.
  • Eligible studies were randomized clinical trials of PN- or PDRN-based interventions in skin rejuvenation, postoperative scar prevention, or wound healing in humans with extractable outcomes; 7 trials involving 183 participants met criteria.
  • Because of clinical and methodological heterogeneity, no meta-analysis was performed; findings were synthesized narratively by clinical domain, with risk of bias assessed using Cochrane RoB 2 (3 low risk, 3 some concerns, 1 high risk).

Limitations

  • The paper states that evidence is limited by small sample sizes, heterogeneous intervention protocols, variable outcome assessment, and lack of standardized PN/PDRN preparations; these factors precluded quantitative synthesis.
  • The paper notes that split-face designs may introduce treatment interaction and diffusion effects, and that small studies are susceptible to imprecise estimates and inflated treatment effects, especially with subjective outcomes.
  • Safety interpretation is constrained by small samples and limited follow-up; the text also makes evident that one included trial had high risk of bias due to no blinding, potential outcome-measurement bias, and manufacturer sponsorship.

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

Integrity signals

Registry

Crossref · 10.7759/cureus.112403

Cites

19 of 19 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

53 of 83 cited sources checked · 37 supported · 0 flagged · accuracy not yet measured

  • Findingcitation

    At week 1, median wound surface area was 5.30 cm2 (range 2.50-8.70) in the PDRN group versus 9.52 cm2 (range 4.80-17.00) in the control group (p=0.007).

    “At week 1, the median wound surface area was 5.30 cm² (range: 2.50-8.70) in the experimental group versus 9.52 cm² (range: 4.80-17.00) in the control group (p=0.007).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [8] Kim JY, Pak CS, Park JH, Jeong JH, Heo CY. Effects of polydeoxyribonucleotide in the treatment of pressure ulcers. J Korean Med Sci. 2014, 29:S222-7. 10.3346/jkms.2014.29.S3.S222 source

      The Results (Evaluation of PDRN effects; page unavailable) report that pressure-ulcer area decreased in the PDRN group, and Methods (Measures; page unavailable) say wound surface area was assessed at week 1. The passages retrieved do not give the claimed week-1 medians, ranges, or p=0.007, so those figures cannot be verified from our copy. (LLM, conf=0.80)

      Experimental — accuracy not yet measured
  • Findingcitation

    CFGS improvements were maintained through the 12-week follow-up.

    “with improvements maintained through the 12-week follow-up”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [12] Jeon W, Park M, Kim SW, Kim J. Efficacy of ionization-adjusted PN filler in minimizing injection pain: a randomized, patient-blinded, split-face study. Aesthetic Plast Surg. 2026, 50:2723-30. 10.1007/s00266-025-05320-x source
  • Interpretationcitation

    The ionization-adjusted PN formulation is non-inferior in aesthetic efficacy to the conventional PN filler.

    “confirming non-inferior aesthetic efficacy for the ionization-adjusted formulation”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [12] Jeon W, Park M, Kim SW, Kim J. Efficacy of ionization-adjusted PN filler in minimizing injection pain: a randomized, patient-blinded, split-face study. Aesthetic Plast Surg. 2026, 50:2723-30. 10.1007/s00266-025-05320-x source
  • Findingcitation

    In Hong et al., no significant pre- to post-treatment differences were observed in conventional needle injection areas for pore index or wrinkle index.

    “whereas no significant pre- to post-treatment differences were observed in the conventional needle injection areas for either parameter.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Hong JY, Lee YH, Kim HJ, Park KY. Therapeutic performance of needle injection versus needle-free jet injector system for polynucleotide filler in skin rejuvenation. J Cosmet Dermatol. 2025, 24:e16595. 10.1111/jocd.16595 source
  • Findingcitation

    In Hong et al., overall patient satisfaction scores were significantly greater following needle-free injection than following conventional injection.

    “Overall patient satisfaction scores were also significantly greater following needle-free injection (4.5±0.53 versus 3.9±0.73; p=0.019).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Hong JY, Lee YH, Kim HJ, Park KY. Therapeutic performance of needle injection versus needle-free jet injector system for polynucleotide filler in skin rejuvenation. J Cosmet Dermatol. 2025, 24:e16595. 10.1111/jocd.16595 source
  • Classified as probably not a substantial claim. 29
  • The quote only partly states this claim. 1
  • May combine two claims. 36

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

    Study design and conductcitation

    This systematic review was conducted in accordance with the PRISMA 2020 statement.

    “This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement [10].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [10] Page MJ, McKenzie JE, Bossuyt PM, et al.. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021, 372:n71. 10.1136/bmj.n71 source

      The Abstract identifies PRISMA 2020 as a guideline for reporting systematic reviews, so this is the correct source for the named statement. But the Scope of the guideline explicitly says PRISMA 2020 is not intended to guide review conduct. The source therefore supports using PRISMA to report the review, not a claim that the review was conducted according to its methods; it also cannot establish whether this particular review adhered to the reporting guidance. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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

    Findingcitation

    In Vera et al., the PDRN group's mean SHI score decreased from 2.83±0.15 to 2.62±0.17.

    “In Group 1, the mean SHI score decreased from 2.83±0.15 to 2.62±0.17 (p=0.001)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [14] Vera V, Praharsini IG, Darwinata AE, Wahyuni N, Wahyuniari IA, Ernawati DK. Comparison of microneedling and polydeoxyribonucleotide salmon 3% versus microneedling and platelet rich plasma in treating wrinkles and facial hyperpigmentation. Aesthet Med. 2025, 11:16753. 10.57662/am.v11i2.16753 source

  • The quote only partly states this claim.

    Findingcitation

    In patients with stage 2-4 pressure ulcers, PDRN treatment produced progressive and statistically significant reductions in wound surface area at all weekly assessment time points compared with controls.

    “Wound surface area, measured using VISITRAK Digital, demonstrated progressive and statistically significant reductions in the PDRN group at all weekly assessment time points compared with controls.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [8] Kim JY, Pak CS, Park JH, Jeong JH, Heo CY. Effects of polydeoxyribonucleotide in the treatment of pressure ulcers. J Korean Med Sci. 2014, 29:S222-7. 10.3346/jkms.2014.29.S3.S222 source

      The Results (Wound surface area; page not provided) report progressively greater reductions in the PDRN group than in controls, significant at each assessment from weeks 1 through 4. The Methods (Measures) confirm use of VISITRAK Digital. However, the Methods (Setting and participants) specify ulcers “higher than stage 2,” so the added claim that the findings apply to stage 2 ulcers is not supported. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    In Yogya et al., wrinkle indentation began to improve earlier on the PN-treated side, with a statistically significant between-group difference at the two-month follow-up.

    “wrinkle indentation began to improve earlier on the PN-treated side, with a statistically significant between-group difference evident at the two-month follow-up (p<0.05; p=0.006).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [7] Yogya Y, Wanitphakdeedecha R, Wongdama S, Nanchaipruek Y, Yan C, Rakchart S. Efficacy and safety of using noninsulated microneedle radiofrequency alone versus in combination with polynucleotides for treatment of periorbital wrinkles. Dermatol Ther (Heidelb). 2022, 12:1133-45. 10.1007/s13555-022-00729-7 source

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

    Findingcitation

    In Vera et al., the PRP group's mean SHI score decreased from 2.76±0.17 to 2.60±0.16.

    “in Group 2 from 2.76±0.17 to 2.60±0.16 (p=0.001)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [14] Vera V, Praharsini IG, Darwinata AE, Wahyuni N, Wahyuniari IA, Ernawati DK. Comparison of microneedling and polydeoxyribonucleotide salmon 3% versus microneedling and platelet rich plasma in treating wrinkles and facial hyperpigmentation. Aesthet Med. 2025, 11:16753. 10.57662/am.v11i2.16753 source

  • May combine two claims.

    Premisecitation

    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].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [5] Kim ST. Comparison of polynucleotide and polydeoxyribonucleotide in dermatology: molecular mechanisms and clinical perspectives. Pharmaceutics. 2025, 17:1024. 10.3390/pharmaceutics17081024 source

      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
    • cites [18] Rho NK, Chilukuri S, Chan G, Kim MJ, Shin J, Suwanchinda A. Expert perspectives: evidence-based applications of polynucleotides (PNs) in aesthetic medicine and dermatology. Clin Cosmet Investig Dermatol. 2026, 19:557226. 10.2147/CCID.S557226 source

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

      Experimental — accuracy not yet measured

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

    Premisecitation

    Recent reviews suggest that PN-based therapies function primarily as biostimulatory agents that improve tissue quality through progressive dermal remodeling rather than immediate structural correction.

    “Recent reviews similarly suggest that PN-based therapies function primarily as biostimulatory agents that improve tissue quality through progressive dermal remodeling rather than immediate structural correction [16,17].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [16] Lampridou S, Bassett S, Cavallini M, Christopoulos G. The effectiveness of polynucleotides in esthetic medicine: a systematic review. J Cosmet Dermatol. 2025, 24:e16721. 10.1111/jocd.16721 source

      The Conclusions describe PN as promoting collagen production and tissue repair, and the Discussion describes a lasting improvement in skin status rather than merely immediate hydration. The Results also report skin-texture improvements over weeks to months. The review does not establish the claim’s specific contrast with immediate structural correction. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [17] Lee KW, Chan KW, Lee A, Lee CH, Wan J, Wong S, Yi KH. Polynucleotides in aesthetic medicine: a review of current practices and perceived effectiveness. Int J Mol Sci. 2024, 25:8224. 10.3390/ijms25158224 source

      Section 2 describes PN as stimulating collagen production and improving skin texture and elasticity, supporting the biostimulatory, tissue-quality part of the claim. Section 3 also reports PN use as a filler for wrinkle correction, while the Conclusions say its mechanism of action has not been objectively demonstrated. The review does not establish that PN works primarily through progressive dermal remodeling rather than immediate structural correction. Page numbers were not provided in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Height VSS subscale scores decreased from 1.27±0.22 to 0.41±0.16 in the PN group, but this did not reach statistical significance (p=0.06).

    “Pliability scores decreased from 1.73±0.16 to 0.59±0.16, and height scores decreased from 1.27±0.22 to 0.41±0.16; however, neither reached statistical significance (p=0.07 and p=0.06, respectively).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Kim JH, Jeong JJ, Lee YI, et al.. Preventive effect of polynucleotide on post-thyroidectomy scars: a randomized, double-blinded, controlled trial. Lasers Surg Med. 2018, 10.1002/lsm.22812 source

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

    Findingown data

    Sample sizes of the included studies ranged from 10 to 42 analyzed participants.

    “Sample sizes ranged from 10 to 42 analyzed participants”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Pliability VSS subscale scores decreased from 1.73±0.16 to 0.59±0.16 in the PN group, but this did not reach statistical significance (p=0.07).

    “Pliability scores decreased from 1.73±0.16 to 0.59±0.16, and height scores decreased from 1.27±0.22 to 0.41±0.16; however, neither reached statistical significance (p=0.07 and p=0.06, respectively).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Kim JH, Jeong JJ, Lee YI, et al.. Preventive effect of polynucleotide on post-thyroidectomy scars: a randomized, double-blinded, controlled trial. Lasers Surg Med. 2018, 10.1002/lsm.22812 source

  • May combine two claims.

    Findingown data

    Among the included trials, four evaluated skin rejuvenation, one evaluated postoperative scar prevention, and two evaluated wound-healing applications.

    “Four studies evaluated skin rejuvenation, one postoperative scar prevention, and two wound-healing applications.”
    • Also stated in: § Review · plain
      “Four studies investigated aesthetic skin rejuvenation, one evaluated postoperative scar prevention following thyroidectomy, and two assessed wound-healing interventions in pressure ulcers and skin-graft donor sites.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    After removal of 18 duplicate records, 56 records remained for title and abstract screening.

    “Following the removal of 18 duplicate records, 56 records remained for title and abstract screening.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Mean VSS scores decreased from 6.05±0.52 at baseline to 2.09±0.47 at 16 weeks in the PN group, compared with a reduction from 6.25±0.59 to 4.01±0.55 in the control group (p<0.05).

    “The mean VSS scores decreased from 6.05±0.52 at baseline to 2.09±0.47 at 16 weeks in the PN group, compared with a reduction from 6.25±0.59 to 4.01±0.55 in the control group (p<0.05).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Kim JH, Jeong JJ, Lee YI, et al.. Preventive effect of polynucleotide on post-thyroidectomy scars: a randomized, double-blinded, controlled trial. Lasers Surg Med. 2018, 10.1002/lsm.22812 source

  • May combine two claims.

    Findingown data

    The most consistent benefits were observed in wound-healing settings, where PDRN accelerated re-epithelialization and shortened healing time compared with controls.

    “The most consistent benefits were observed in wound-healing settings, where PDRN accelerated re-epithelialization and shortened healing time compared with controls.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: PNs and PDRNs are highly purified DNA-derived compounds that exhibit biological activities supporting tissue repair and regeneration.

  • May combine two claims.

    Findingcitation

    Patient scar perception scores improved from 2.86±0.18 to 3.27±0.18 in the PN group, compared with minimal change from 2.91±0.16 to 2.90±0.23 in the control group, but between-group differences did not reach statistical significance (p=0.23).

    “Patient scar perception scores improved from 2.86±0.18 to 3.27±0.18 in the PN group, compared with minimal change from 2.91±0.16 to 2.90±0.23 in the control group, though between-group differences did not reach statistical significance (p=0.23).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Kim JH, Jeong JJ, Lee YI, et al.. Preventive effect of polynucleotide on post-thyroidectomy scars: a randomized, double-blinded, controlled trial. Lasers Surg Med. 2018, 10.1002/lsm.22812 source

  • May combine two claims.

    Findingown data

    Five full-text articles were excluded: two for non-randomized design, one review or expert consensus publication, one protocol publication without clinical outcome data, and one for insufficient extractable quantitative outcome data.

    “Following full-text review, five articles were excluded for the following reasons: non-randomized study design (n=2), review article or expert consensus publication (n=1), protocol publication without clinical outcome data (n=1), and insufficient extractable quantitative outcome data (n=1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Within the PN group, mean scar height decreased from 0.46±0.06 at baseline to 0.23±0.03 at 16 weeks, whereas in the control group it decreased from 0.38±0.04 to 0.29±0.03.

    “Within the PN group, the mean scar height decreased from 0.46±0.06 at baseline to 0.23±0.03 at 16 weeks, whereas in the control group, it decreased from 0.38±0.04 to 0.29±0.03.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Kim JH, Jeong JJ, Lee YI, et al.. Preventive effect of polynucleotide on post-thyroidectomy scars: a randomized, double-blinded, controlled trial. Lasers Surg Med. 2018, 10.1002/lsm.22812 source

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

    Findingown data

    Follow-up durations of the included studies varied from two weeks to six months.

    “follow-up durations varying from two weeks to six months”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Across the included studies, PN and PDRN therapies improved wrinkle-related outcomes, scar quality, wound-healing metrics, and patient-reported satisfaction.

    “Across studies, PN and PDRN therapies improved wrinkle-related outcomes, scar quality, wound-healing metrics, and patient-reported satisfaction.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Skin rejuvenation, postoperative scar prevention, and wound healing share overlapping biological pathways that may respond to similar regenerative mechanisms.
    • Rests on an assumption: PNs and PDRNs are highly purified DNA-derived compounds that exhibit biological activities supporting tissue repair and regeneration.

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

    Findingcitation

    Split-face designs were employed in three of the four aesthetic rejuvenation studies.

    “Split-face designs were employed in three of the four aesthetic rejuvenation studies”
    Quote in the paperNot a substantial claim

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

    Findingreasoning

    Parallel-group designs were used across the remaining included studies.

    “whereas parallel-group designs were used across the remaining studies.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Twelve full-text articles were retrieved and assessed for eligibility.

    “Twelve full-text articles were subsequently retrieved and assessed for eligibility.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    A total of 74 records were identified through database searching.

    “A total of 74 records were identified through database searching.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The evidence base comprised both parallel-group randomized controlled trials and randomized split-face clinical trials.

    “The evidence base comprised both parallel-group randomized controlled trials and randomized split-face clinical trials.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The PN group achieved greater than 50% reduction in VSS score, satisfying the predefined criterion for treatment success.

    “The PN group achieved greater than 50% reduction in VSS score, satisfying the predefined criterion for treatment success.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Kim JH, Jeong JJ, Lee YI, et al.. Preventive effect of polynucleotide on post-thyroidectomy scars: a randomized, double-blinded, controlled trial. Lasers Surg Med. 2018, 10.1002/lsm.22812 source

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

    Findingown data

    The included studies were conducted across Asian and European populations.

    “conducted across Asian and European populations”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Both groups demonstrated improvement in Melanin Index (MI), but the reduction was less prominent in the PN group (PN: 148.06±10.04 to 134.76±8.57; control: 147.56±9.79 to 113.41±9.37; p<0.05).

    “Although both groups demonstrated improvement in the Melanin Index (MI), the reduction was less prominent in the PN group (PN group: 148.06±10.04 to 134.76±8.57; control group: 147.56±9.79 to 113.41±9.37; p<0.05).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Kim JH, Jeong JJ, Lee YI, et al.. Preventive effect of polynucleotide on post-thyroidectomy scars: a randomized, double-blinded, controlled trial. Lasers Surg Med. 2018, 10.1002/lsm.22812 source

  • May combine two claims.

    Findingown data

    Four included studies evaluated PN-based interventions, whereas three investigated PDRN-based therapies.

    “Four studies evaluated PN-based interventions, whereas three studies investigated PDRN-based therapies across skin rejuvenation, scar management, and wound-healing indications.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Publication years of the included studies ranged from 2004 to 2025.

    “Publication years ranged from 2004 to 2025”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Of the 56 screened records, 44 were excluded because they did not meet the predefined eligibility criteria.

    “Of these, 44 records were excluded because they did not meet the predefined eligibility criteria.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Reported adverse events were generally mild, transient, and localized to treatment sites.

    “Reported adverse events were generally mild, transient, and localized to treatment sites.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Complete re-epithelialization occurred at a mean of 12.5 days (range 9-20) in the PDRN ointment group compared with 24.45 days (range 17-41) in the control group, representing an approximate 50% reduction in healing time.

    “Complete re-epithelialization occurred at a mean of 12.5 days (range: 9-20) in the PDRN group compared with 24.45 days (range: 17-41) in the control group, representing an approximate 50% reduction in healing time.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Valdatta L, Thione A, Mortarino C, Buoro M, Tuinder S. Evaluation of the efficacy of polydeoxyribonucleotides in the healing process of autologous skin graft donor sites: a pilot study. Curr Med Res Opin. 2004, 20:403-8. 10.1185/030079904125003116 source

  • May combine two claims.

    Findingcitation

    PDRN-treated patients were nearly completely asymptomatic, with only four cases of moderate symptoms, while the control group included four cases of serious symptoms and nine cases of marked symptoms.

    “Subjective symptom assessment demonstrated that PDRN-treated patients were nearly completely asymptomatic, with only four cases of moderate symptoms reported, while the control group included four cases of serious symptoms and nine cases of marked symptoms”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Valdatta L, Thione A, Mortarino C, Buoro M, Tuinder S. Evaluation of the efficacy of polydeoxyribonucleotides in the healing process of autologous skin graft donor sites: a pilot study. Curr Med Res Opin. 2004, 20:403-8. 10.1185/030079904125003116 source

  • May combine two claims.

    Findingreasoning

    PDRN was predominantly investigated in wound-healing settings, where treatment effects were generally robust and objectively measurable.

    “PDRN was predominantly investigated in wound-healing settings, where treatment effects were generally robust and objectively measurable.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    No infections were recorded in the PDRN ointment group, whereas nine infections occurred in the control group, representing a 45% infection rate.

    “no infections were recorded in the PDRN group throughout the study period, whereas nine infections occurred in the control group, representing a 45% infection rate.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Valdatta L, Thione A, Mortarino C, Buoro M, Tuinder S. Evaluation of the efficacy of polydeoxyribonucleotides in the healing process of autologous skin graft donor sites: a pilot study. Curr Med Res Opin. 2004, 20:403-8. 10.1185/030079904125003116 source

  • May combine two claims.

    Findingreasoning

    Improvements were observed in wrinkle severity, skin texture, and patient satisfaction; however, effect sizes were generally smaller, and outcome assessment was considerably more heterogeneous.

    “Improvements were observed in wrinkle severity, skin texture, and patient satisfaction; however, effect sizes were generally smaller, and outcome assessment was considerably more heterogeneous.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Aesthetic outcomes are influenced by baseline photoaging severity, treatment technique, patient perception, and assessment methodology.
    • Rests on an assumption: Structural alterations associated with skin aging develop gradually and may require prolonged remodeling before clinically meaningful differences become apparent.

  • May combine two claims.

    Findingown data

    PDRN administration was associated with significant reductions in wound surface area, improved healing scores, accelerated re-epithelialization, and shorter healing times.

    “PDRN administration was associated with significant reductions in wound surface area, improved healing scores, accelerated re-epithelialization, and shorter healing times.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Most studies enrolled relatively small cohorts, and several included fewer than 30 analyzed participants.

    “Most studies enrolled relatively small cohorts, and several included fewer than 30 analyzed participants.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Small studies are more susceptible to imprecise effect estimates and inflation of treatment effects, particularly when subjective outcome measures are used.

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

    Study design and conductnone given

    Additional studies were identified through manual screening of reference lists from eligible articles.

    “Additional studies were identified through manual screening of reference lists from eligible articles.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    Findings were synthesized narratively and organized according to predefined clinical domains including skin rejuvenation, postoperative scar prevention, and wound healing.

    “Findings were synthesized narratively and organized according to predefined clinical domains, including skin rejuvenation, postoperative scar prevention, and wound healing.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    Split-face designs enable within-subject comparisons and reduce confounding from interindividual variability.

    “enabling within-subject comparisons and reducing confounding from interindividual variability”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Disagreements during screening and eligibility assessment were resolved through discussion and consensus, with consultation of a third reviewer when necessary.

    “Disagreements during screening and eligibility assessment were resolved through discussion and consensus, with consultation of a third reviewer when necessary.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Data extraction was performed independently by two reviewers using a standardized form developed a priori.

    “Data extraction was performed independently by two reviewers using a standardized form developed a priori.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The review protocol was prospectively registered in PROSPERO with registration number CRD420261418096.

    “The review protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD420261418096).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Risk of bias assessments were incorporated into the interpretation of the evidence.

    “Risk of bias assessments were incorporated into the interpretation of the evidence.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Two reviewers independently assessed each study for risk of bias.

    “Two reviewers independently assessed each study”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Methodological quality was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool.

    “Methodological quality was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Two reviewers independently screened titles and abstracts for eligibility.

    “Two reviewers independently screened titles and abstracts for eligibility.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    A comprehensive electronic literature search was conducted in PubMed, Embase, and CENTRAL from database inception through January 2026.

    “A comprehensive electronic literature search was conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from database inception through January 2026.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Outcome assessment incorporated validated clinical grading scales, objective imaging modalities, wound-healing metrics, and patient-reported outcome measures.

    “Outcome assessment incorporated validated clinical grading scales, objective imaging modalities, wound-healing metrics, and patient-reported outcome measures.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    For split-face studies, data from treatment and comparator sides were extracted separately where applicable.

    “For split-face studies, data from treatment and comparator sides were extracted separately where applicable.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Clinical benefits were observed across all evaluated domains, with the most consistent effects reported in wound-healing applications.

    “Clinical benefits were observed across all evaluated domains, with the most consistent effects reported in wound-healing applications.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Aesthetic outcomes are influenced by baseline photoaging severity, treatment technique, patient perception, and assessment methodology.
    • Rests on an assumption: Structural alterations associated with skin aging develop gradually and may require prolonged remodeling before clinically meaningful differences become apparent.

  • May combine two claims.

    Study design and conductreasoning

    The available evidence remains limited by small sample sizes, heterogeneous intervention protocols, and variability in outcome assessment.

    “The available evidence remains limited by small sample sizes, heterogeneous intervention protocols, and variability in outcome assessment.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Small studies are more susceptible to imprecise effect estimates and inflation of treatment effects, particularly when subjective outcome measures are used.

  • May combine two claims.

    Study design and conductown data

    Overall, three included studies were judged as having low risk of bias, three as having some concerns, and one as having high risk of bias.

    “Overall, three studies were judged as having a low risk of bias, three studies were judged as having some concerns, and one study was judged as having a high risk of bias.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    Three rejuvenation studies employed split-face designs, which reduce interindividual variability and enhance statistical efficiency by allowing participants to serve as their own controls.

    “Three rejuvenation studies employed split-face designs, which reduce interindividual variability and enhance statistical efficiency by allowing participants to serve as their own controls.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Split-face designs reduce interindividual variability and enhance statistical efficiency by allowing participants to serve as their own controls.

  • May combine two claims.

    Interpretationreasoning

    Overall, PN and PDRN therapies demonstrated favorable safety profiles and promising efficacy in enhancing tissue repair and skin quality.

    “Overall, these therapies demonstrated favorable safety profiles and promising efficacy in enhancing tissue repair and skin quality.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Aesthetic outcomes are influenced by baseline photoaging severity, treatment technique, patient perception, and assessment methodology.
    • Rests on an assumption: Structural alterations associated with skin aging develop gradually and may require prolonged remodeling before clinically meaningful differences become apparent.

  • May combine two claims.

    Interpretationreasoning

    Direct comparative studies remain limited, and current evidence does not permit definitive conclusions regarding the relative efficacy of PN and PDRN for specific clinical indications.

    “However, direct comparative studies remain limited, and current evidence does not permit definitive conclusions regarding the relative efficacy of PN and PDRN for specific clinical indications.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The absence of standardized PN and PDRN preparations represents a major challenge for evidence synthesis and currently limits the identification of optimal treatment protocols.

    “Notably, the absence of standardized PN and PDRN preparations represents a major challenge for evidence synthesis and currently limits the identification of optimal treatment protocols.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Aesthetic interventions primarily address chronic structural alterations associated with skin aging, whereas wound-healing applications involve active biological processes that may be inherently more responsive to regenerative stimulation.

    “Whereas aesthetic interventions primarily address chronic structural alterations associated with skin aging, wound-healing applications involve active biological processes that may be inherently more responsive to regenerative stimulation.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Risk of bias was assessed using the RoB 2 tool across five domains.

    “Risk of bias was assessed using the RoB 2 tool across five domains.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    Heterogeneity across study designs and outcome measures precluded quantitative synthesis and restricted meaningful comparison between formulations.

    “Furthermore, heterogeneity across study designs and outcome measures precluded quantitative synthesis and restricted meaningful comparison between formulations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Nucleotide-derived therapies may enhance angiogenesis, fibroblast proliferation, extracellular matrix remodeling, and collagen deposition during tissue repair.

    “These findings are consistent with previous evidence indicating that nucleotide-derived therapies may enhance angiogenesis, fibroblast proliferation, extracellular matrix remodeling, and collagen deposition during tissue repair [15].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Colangelo MT, Galli C, Guizzardi S. The effects of polydeoxyribonucleotide on wound healing and tissue regeneration: a systematic review of the literature. Regen Med. 2020, 10.2217/rme-2019-0118 source

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Prospective registration, adherence to PRISMA recommendations, and structured risk of bias assessment enhanced methodological rigor and transparency.

    “while prospective registration, adherence to PRISMA recommendations, and structured risk of bias assessment enhanced methodological rigor and transparency.”
    Quote in the paperSubstantial claim
63 of 63

  • The paper relies on this without support.

    Current treatment strategies for skin aging, postoperative scars, and impaired wound healing often have variable effects and may not directly target the molecular pathways involved in tissue regeneration and long-term remodeling.

    “Although these approaches may improve clinical appearance, their effects are often variable and may not directly target the molecular pathways involved in tissue regeneration and long-term tissue remodeling.”

  • The paper relies on this without support.

    Skin rejuvenation, postoperative scar prevention, and wound healing share overlapping biological pathways that may respond to similar regenerative mechanisms.

    “skin rejuvenation, postoperative scar prevention, and wound healing are often investigated separately despite sharing overlapping biological pathways that may respond to similar regenerative mechanisms.”

  • The paper relies on this without support.

    PNs and PDRNs are highly purified DNA-derived compounds that exhibit biological activities supporting tissue repair and regeneration.

    “These highly purified DNA-derived compounds exhibit biological activities that support tissue repair and regeneration.”

  • The paper relies on this without support.

    Aesthetic outcomes are influenced by baseline photoaging severity, treatment technique, patient perception, and assessment methodology.

    “Unlike wound-healing endpoints, aesthetic outcomes are influenced by baseline photoaging severity, treatment technique, patient perception, and assessment methodology.”

  • The paper relies on this without support.

    Structural alterations associated with skin aging develop gradually and may require prolonged remodeling before clinically meaningful differences become apparent.

    “Furthermore, structural alterations associated with skin aging develop gradually and may require prolonged remodeling before clinically meaningful differences become apparent.”

  • The paper relies on this without support.

    Small studies are more susceptible to imprecise effect estimates and inflation of treatment effects, particularly when subjective outcome measures are used.

    “Small studies are more susceptible to imprecise effect estimates and inflation of treatment effects, particularly when subjective outcome measures are used.”

  • The paper relies on this without support.

    Split-face designs reduce interindividual variability and enhance statistical efficiency by allowing participants to serve as their own controls.

    “Three rejuvenation studies employed split-face designs, which reduce interindividual variability and enhance statistical efficiency by allowing participants to serve as their own controls.”
7 of 7

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.

  • Thyroidectomy trial is described as PN but cited as PDRN

    Minor

    The introduction describes the thyroidectomy scar study cited as [6] as a PN-based therapy, but reference [6] identifies its intervention as polydeoxyribonucleotide (PDRN). The paper otherwise distinguishes PN from PDRN.

1 of 1

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Authors
Alhussain, A. M., Turki M. Albusayys, S., Alfhadi, M. A., Bu Mozah, S. A., AlShammari, S. S. S., Alanazi, H. A. M., Adil Alqazanli, S., Nouruldeen Alabdullah, A., M. ALrashidi, N., Almazrou, A. A., & Alshehri, A. F.
Affiliations
  • Almaarefa University (SA)
  • Najran University (SA)
  • Imam Mohammad ibn Saud Islamic University (SA)
Corresponding author
Alshehri, Abdulelah F
Venue
Cureus
Publisher
Springer Science and Business Media LLC
Published
2026-07-10
Volume
18
Issue
7
Pages
e112403-e112403
ISSN
2168-8184 (ISSN-L)
DOI
10.7759/cureus.112403
PMC
PMC13453133
OpenAlex
W7167935308
Cited by
1
References
18
Citations by year
2026: 1
FWCI
0.99
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cureus (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
  • Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
Keywords
polynucleotides, polydeoxyribonucleotide, skin rejuvenation, wound healing, re-epithelialization, wrinkle reduction, scar quality, patient-reported satisfaction

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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