Polynucleotides and PDRN for skin: what the randomised trials show
Both are purified DNA fragments, most often extracted from salmon or trout sperm — but PDRN and polynucleotides are not interchangeable terms, and the difference is chain length. This page separates the two, then reports what the randomised evidence supports and where it stops.
Agendar ConsultaPDRN and polynucleotides are not the same molecule
PDRN (polydeoxyribonucleotide) and polynucleotides (PN) are purified DNA fragments from the same raw material — injectable grades come mostly from the sperm of chum salmon or rainbow trout — but the two names are not synonyms: they describe different chain lengths, and chain length changes how much water the material holds, how viscous it is and how long it lasts in the skin.
The confusion is not the patient's fault. A narrative review published in Biomolecules in 2025 exists precisely to name it: it states that "PDRN" and "PN" have been used interchangeably in the scientific literature and in the aesthetic market to describe polymers of very different molecular weights, causing confusion within the medical and scientific communities. To resolve the ambiguity, those authors propose a structural threshold they name themselves, the "Marques Polynucleotide Cutoff", set at 1500 kDa: below it the material should be called PDRN, at or above it PN.
That is a proposal for standardising nomenclature, not a settled position of the field — and the field shows it. A 2026 review of the periorbital region writes of "polynucleotides (PN), particularly polydeoxyribonucleotides (PDRN)", treating PDRN as a subtype within polynucleotides instead.
Two details from the 2025 review explain the drift. The first drug approved with this active principle, in 1994, came from human placenta and has an average molecular weight of 350 kDa; manufacturing later moved to salmon and trout sperm, which is why "salmon DNA injections" names the same category. And one limit survives the debate: that review notes the exact chain size is usually undisclosed for commercial PN hydrogels.
What the molecule is meant to do in skin
The mechanism has a counter-intuitive first step: the polymer has to be broken down before it does anything. According to the 2025 narrative review, PDRN and PN are degraded in situ by the body's own nucleases, and it is the released deoxyribonucleotides — not the intact chain — that bind the adenosine A2A receptor on fibroblasts. Nothing enters the nucleus and nothing is added to the patient's genetic material.
That review groups the downstream effects into three: resolution of inflammation, with lower pro-inflammatory cytokines such as TNF-alpha, IL-6 and IL-8 and more of the anti-inflammatory IL-10; proliferation, through VEGF secretion, new vessels and fibroblast migration; and remodelling, in which fibroblasts produce collagen types I and III, elastin and fibrinogen. A parallel salvage pathway recycles the nucleotides, lowering the energy cost of matrix protein synthesis.
This is where the category diverges from the classic biostimulators. The same review points out that calcium hydroxylapatite, poly-L-lactic acid and polycaprolactone rely on an induced local inflammatory response to push fibroblasts into producing collagen, whereas PDRN induces protein production by decreasing inflammation. Those authors add that, to the best of their knowledge, there are no reported cases of nodule or granuloma formation after PN-based filler injections — a statement about the published record as they found it, not an assurance about any product or injector.
Chain length matters again here. Because a longer chain offers less surface area to the nucleases, that review describes a PN hydrogel as degrading more slowly than a liquid PDRN formulation, and so stimulating the skin for longer; longer chains also hold more water, which is why high-molecular-weight PN can be formulated as a viscous hydrogel with some volumising use, while PDRN in solution does not volumise.
The randomised evidence, and where it stops
Two recent reviews bracket the picture, and they do not agree. A systematic review published in the Journal of Cosmetic Dermatology in 2025 gathered nine studies from 2014 to 2022, totalling 219 patients treated with polynucleotides, and graded them low to moderate quality; its authors report that variation in settings and outcomes precluded a meta-analysis and that none of the included studies achieved full scores in the critical appraisal. Six of the nine measured wrinkle reduction and all six reported improvement, but only half reached statistical significance.
The second is stricter, and that is what makes it valuable: a systematic review published in Cureus in 2026 restricted inclusion to randomised clinical trials and found seven, involving 183 participants — four in skin rejuvenation, one in scar prevention, two in wound healing. Its central finding is not the one this category's marketing would predict: the most consistent benefits appeared in wound healing, where PDRN accelerated re-epithelialisation and shortened healing time compared with controls, while the aesthetic results were favourable but more modest. Using the RoB 2 tool it judged three trials at low risk of bias, three as raising concerns and one at high risk.
The shape of those four aesthetic trials deserves stating plainly. Among the four skin-rejuvenation trials included in that review, none compared injected polynucleotides on their own against an inactive control: two compared one delivery method or formulation against another, and two added the nucleotide to a device-based treatment. In its split-face trial of radiofrequency microneedling in 29 women, wrinkle indentation improved earlier on the polynucleotide-treated side — but that review records no significant difference in maximum wrinkle depth between sides at any follow-up point.
The one trial that set a nucleotide against an established active comparator is the one patients ask about: in 24 women aged 30 to 50, mean Lemperle wrinkle scores fell from 2.33 to 1.00 with microneedling plus PDRN and from 2.33 to 1.50 with microneedling plus platelet-rich plasma at six weeks, favouring PDRN, while the reduction in the Skin Hyperpigmentation Index was comparable. Neither review reported a serious treatment-related adverse event, and both attribute that to small samples and short follow-up.
Under the eye: polynucleotides or hyaluronic acid filler?
A narrative review published in the Journal of Clinical Medicine in 2026 was written to address this comparison. Its framing is that the two are complementary rather than competing: hyaluronic acid remains the cornerstone for volume loss and structural deficiency, while polynucleotides contribute to skin quality, particularly in thin or oedema-prone periorbital tissue. That review describes infraorbital skin as exceptionally thin, approximately 0.5 mm, and HA fillers act by occupying space and attracting water — which is what corrects a hollow and also what can worsen fluid retention in a region already prone to lymphatic stasis.
It lists the characteristic complications accordingly — persistent malar oedema, the bluish Tyndall effect, contour irregularity, and the rare but vision-threatening vascular occlusion. Citing a long-term follow-up series of 147 patients, it reports malar oedema in 11%, blue-grey dyschromia in 31.3% and contour irregularities in 30.5%, with 90% graded mild.
On the other side, that review reports a randomised, double-blind, split-face trial in 27 subjects comparing a polynucleotide filler with non-cross-linked hyaluronic acid in the periorbital area: no significant difference in global aesthetic or visual analogue scores, while objective measures favoured the polynucleotide side, with improvement rates in elasticity, hydration, roughness and pore volume generally higher or better sustained. The 2025 systematic review records that trial's product as a Rejuran-branded polynucleotide at 20 mg/mL against a non-cross-linked HA booster — which is not a cross-linked tear-trough filler.
| What you want changed | Polynucleotides / PDRN | Hyaluronic acid filler |
|---|---|---|
| A visible hollow or tear trough | Minimal volumetric support; that review states it cannot address moderate to severe tear trough deformity | Preferred for volume loss, corrected immediately |
| Crepey, thin skin and fine lines | Where that review positions it: dermal thinning, crepiness, fine rhytides | Limited impact on elasticity, hydration and texture |
| Oedema-prone lower eyelid | Favoured by the consensus work that review cites | Hydrophilic action may aggravate fluid retention |
| Reversibility | No enzyme reverses it; nucleases degrade it | Reversible with hyaluronidase — which that review calls a reactive measure after a complication, not a mitigation of risk |
| Both problems at once | Sequenced after structure | First, for the deficit — at or below 0.5 mL per eye, midface supported first |
Cautions from the same review keep this from being oversold. It states that direct head-to-head comparative studies between PN and HA remain scarce, that comparative data beyond 12 months are largely unavailable, and that long-term safety data for polynucleotides in the periorbital region remain sparse. It also warns against assuming that mechanistic superiority equals clinical superiority.
Scars and post-procedure healing: the strongest part of the file
The 2026 randomised-trials review observed that treatment effects appeared to increase progressively from aesthetic rejuvenation to scar modulation and then to wound repair. Its proposed explanation is biological: wound healing involves active inflammatory and proliferative pathways, a more responsive environment for a regenerative signal than chronically aged skin.
The scar trial in that review is a randomised, double-blinded controlled trial in 42 patients after total thyroidectomy. All received one session of fractional laser with concomitant injection of either polynucleotide or saline, then two further injections two weeks apart. Mean Vancouver Scar Scale scores fell from 6.05 at baseline to 2.09 at 16 weeks in the polynucleotide group, against 6.25 to 4.01 in the control group. Reading the subscales keeps the claim proportionate: pigmentation and vascularity improved significantly, while pliability and height did not reach statistical significance. No patient in either group developed a hypertrophic scar or keloid during the follow-up.
The two wound-healing trials sit further from aesthetics. PDRN added to standard care in 23 analysed patients with pressure ulcers produced significantly smaller wounds at every weekly assessment through four weeks; and in 40 patients whose skin-graft donor sites were dressed with either PDRN ointment or conventional gauze, mean re-epithelialisation at day 15 was 98.5% against 53.5%. That donor-site trial is also the one its authors judged at high risk of bias, citing absence of blinding and manufacturer sponsorship, so its direction deserves more confidence than its exact magnitude.
The bridge back to aesthetics is narrow. Those trials all combined the nucleotide with something else — laser in one case, standard wound care in the others — and the acne-scar trial in the earlier systematic review was a 20-patient randomised comparison of polynucleotide against saline. That supports using this category as an adjunct inside a scar-remodelling protocol, not as a scar-erasing treatment.
Sessions, interval and a realistic expectation
There is no single protocol, and the sources say so in as many words. In the nine studies gathered by the 2025 systematic review, the facial indications used between two and four sessions at intervals of one to four weeks, most commonly two weeks apart, with follow-up from 12 to 28 weeks; the outlier, twelve weekly sessions, was a hair-loss study in a different indication. Doses clustered around 1.0 mL of a 20 mg/mL polynucleotide per area, through fine 30G to 34G needles.
The 2026 periorbital review points in a compatible direction, citing consensus guidance that suggests face and periocular protocols of three to four sessions two to three weeks apart followed by spaced maintenance, while stating that optimal long-term intervals remain undefined. It also describes priming — two to four polynucleotide sessions before a filler — and notes that maintenance is typically necessary to sustain results.
What the reviews describe is consistent and unglamorous: improvements in fine lines, texture, elasticity, hydration and luminosity, developing gradually over weeks to months, statistically significant but moderate, with satisfaction reported as moderate to high. Someone expecting the effect of a filler or of a lifting procedure will be disappointed by this category even when it performs as the literature says it does.
On cost, in Brazilian reais: an isolated PDRN session in Brasília sits between R$ 1.900 and R$ 2.900, and the three-session protocol between R$ 4.500 and R$ 7.500, varying with the area treated and the product used. That range is for PDRN specifically: the 2025 narrative review records that injectable-grade PN carries a higher price than injectable-grade PDRN, potentially up to twice as much. The plan is defined at an in-person assessment with Dr. Thiago Perfeito, CRM-DF 23199, in Brasília.
Who this does not suit
The clearest non-candidate is the one the periorbital review identifies outright: the patient whose dominant complaint is tear-trough hollowing, volume loss or contour deficiency. That review states that polynucleotides provide minimal volumetric support and that such patients may see limited improvement with polynucleotide monotherapy, which is why it calls appropriate selection critical. Offering this category to a face that needs structure postpones the treatment that would have worked.
- Anyone who needs a visible change on a specific date. The published outcomes are gradual and moderate in magnitude, with maintenance normally part of the plan.
- Anyone unwilling to complete a series. Every facial protocol in the reviewed literature involved two to four sessions. A single session is not the intervention that was studied.
- Anyone treating the periorbital region who wants long-term safety certainty. The 2026 review states that long-term safety data for polynucleotides in this region remain sparse.
As with any injectable, active infection at the intended site and known hypersensitivity to a component of the product are reasons to postpone, and pregnancy or breastfeeding should be disclosed at assessment. One question is specific to this category: ask for the commercial name and registration number of the exact material to be injected, and check that registration with the health authority beforehand — registration belongs to a product, never to a class. It is also reasonable to confirm the physician's active registration, in Brazil at cfm.org.br.
No commercial relationship with any manufacturer
This page discusses a category of injectable, not a brand, and Dr. Thiago Perfeito's practice holds no commercial relationship, sponsorship, consultancy or financial arrangement with any manufacturer or distributor of PDRN, polynucleotides or hyaluronic acid fillers. Where a brand appears, the criterion is declared: Rejuran is a Korean product in this category, named because the 2025 systematic review's table of included studies records it as the material used in two of the trials discussed here — a randomised comparison in crow's feet and the periorbital split-face trial against non-cross-linked hyaluronic acid. Naming it identifies what was tested; it does not recommend it over competitors.
The four sources are not equally disinterested. The 2025 narrative review that proposes the PDRN/PN cutoff declares no external funding, but several authors were employed by or consulting for companies in this sector during the study. The 2025 systematic review was funded by a doctoral fellowship, with two of its four authors declaring roles with a polynucleotide manufacturer or its distributor. The two 2026 reviews both declare no funding for the work and no competing financial relationships. None of the four was designed to settle a brand comparison, and none is quoted here as doing so.
None of this is settled by reading a page. The evidence above is strong enough to make polynucleotides a reasonable component of a skin-quality protocol, and honest enough to keep them out of the role of a filler or a lifting procedure.
Frequently asked questions about polynucleotides and PDRN
Do polynucleotides work?
For skin quality, the published evidence supports a real but moderate effect. A 2025 systematic review of nine studies and 219 patients found improvements in wrinkles, texture and elasticity, but graded the studies as low to moderate quality and reported that only half of the trials measuring wrinkle reduction reached statistical significance. A stricter 2026 systematic review, limited to seven randomised trials with 183 participants, found the most consistent benefits in wound healing rather than in aesthetic rejuvenation, where results were favourable but more modest. Neither review reported a serious treatment-related adverse event, and both attributed caution to small samples and short follow-up.
What is the difference between PDRN and polynucleotides?
Chain length. Both are purified DNA fragments from the same family of raw material, but a 2025 narrative review in Biomolecules proposes a structural cutoff at 1500 kDa: below it the material should be called PDRN, at or above it polynucleotide (PN). Longer chains hold more water, form more viscous hydrogels and are broken down more slowly by the body's own enzymes, so they stimulate the skin for longer. That cutoff is a proposal for standardising nomenclature rather than a settled position of the field — a 2026 review instead describes PDRN as a subtype within polynucleotides.
Polynucleotides or filler under the eye — which is better?
They answer different questions. A 2026 narrative review on periorbital rejuvenation positions hyaluronic acid filler as the preferred option for tear-trough hollowing and volume loss, with immediate correction, and polynucleotides for dermal thinning, crepey skin and fine lines, with gradual improvement over weeks. In the randomised split-face trial of 27 subjects it reports, polynucleotide and non-cross-linked hyaluronic acid produced no significant difference in global aesthetic scores, while objective measures of elasticity, hydration, roughness and pore volume favoured the polynucleotide side. For a patient with both a hollow and poor skin quality, that review recommends combining the two rather than choosing between them.
Is Rejuran the same as PDRN?
Rejuran is a Korean commercial product in the PDRN/polynucleotide category, not a separate class of treatment — which is why searches often mix the brand with the generic term. The 2025 systematic review discussed on this page records a Rejuran-branded polynucleotide at 20 mg/mL as the material used in two of the trials it included: a randomised comparison in crow's feet and a periorbital split-face trial against non-cross-linked hyaluronic acid. The clinical reasoning applies to any product in the category, provided the manufacturer declares molecular weight, concentration and regulatory registration for that specific material.
Are salmon DNA injections and polynucleotides the same thing?
Yes, in practice. According to the 2025 narrative review, injectable-grade PDRN and polynucleotides are now sourced mainly from the sperm of chum salmon and rainbow trout, purified into DNA fragments, which is where the popular name comes from. The first approved drug with this active principle, in 1994, was extracted from human placenta instead and has an average molecular weight of 350 kDa. Nothing in the injected material enters the patient's cell nucleus or alters their own DNA — the fragments are broken down locally and act as a signal on the adenosine A2A receptor on fibroblasts.
How many PDRN sessions are needed, and how far apart?
There is no single validated protocol, and the sources say so explicitly. In the facial indications gathered by the 2025 systematic review, protocols used two to four sessions at intervals of one to four weeks, most commonly two weeks apart, with follow-up from 12 to 28 weeks. A 2026 periorbital review cites consensus guidance suggesting three to four face or periocular sessions two to three weeks apart followed by spaced maintenance, while stating that optimal long-term intervals remain undefined. Maintenance is typically necessary to sustain results, which is worth factoring into the cost before starting.
How much do polynucleotide and PDRN treatments cost in Brasília?
In Brazilian reais, an isolated PDRN session in Brasília sits between R$ 1.900 and R$ 2.900, and the standard three-session protocol between R$ 4.500 and R$ 7.500, varying with the area treated and the product used. That range refers to PDRN specifically: the 2025 narrative review records that injectable-grade high-molecular-weight polynucleotide costs more than injectable-grade PDRN, potentially up to twice as much. Before comparing quotes, ask which material will be used, at what concentration, and how many sessions the figure covers. The final plan is defined at an in-person assessment.
Does PDRN help with scars?
The scar evidence is among the stronger parts of this file, with a narrow scope. In a randomised, double-blinded trial of 42 patients after total thyroidectomy, reported in a 2026 review of randomised trials, Vancouver Scar Scale scores fell from 6.05 to 2.09 at 16 weeks with polynucleotide injections combined with fractional laser, against 6.25 to 4.01 with laser and saline; the pigmentation and vascularity subscales improved significantly, while pliability and height did not reach significance. An earlier 20-patient randomised trial compared polynucleotide against saline in acne scars. That supports use as an adjunct within a scar-remodelling protocol, not as a scar-erasing treatment.
References
- Marques C, Porcello A, Cerrano M et al. From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules. Biomolecules. 2025;15(1). PMID: 39858543 · doi:10.3390/biom15010148
- Lampridou S, Bassett S, Cavallini M et al. The Effectiveness of Polynucleotides in Esthetic Medicine: A Systematic Review. J Cosmet Dermatol. 2025;24(2):e16721. PMID: 39645667 · doi:10.1111/jocd.16721
- Alhussain AM, Turki M Albusayys S, Alfhadi MA et al. Polynucleotides and Polydeoxyribonucleotides for Skin Rejuvenation, Postoperative Scar Prevention, and Wound Healing: A Systematic Review of Randomized Clinical Trials. Cureus. 2026;18(7):e112403. PMID: 42572627 · doi:10.7759/cureus.112403
- Khan RS, Hafeez K. Hyaluronic Acid Fillers Versus Polynucleotides for Under-Eye Rejuvenation. J Clin Med. 2026;15(13). PMID: 42452433 · doi:10.3390/jcm15134971
Reviewed by Dr. Thiago Perfeito — Aesthetic and Regenerative Medicine, CRM-DF 23199. Updated on .
Not sure whether polynucleotides are the right tool for your skin?
This category treats skin quality, not volume — and telling those two complaints apart is the whole decision. Dr. Thiago Perfeito can assess which applies to your case during a consultation in Brasília.