In short

  • They are chains of purified DNA, usually of fish origin, infiltrated into the dermis. Preparations of shorter fragments are usually labelled PDRN.
  • They are not a filler. They add no volume and do not correct a fold. They work on the quality of the skin.
  • The published evidence is promising but thin and heterogeneous: nine scientific studies, of moderate quality, and no consensus on how to use them optimally.
  • Where they have been studied most in facial aesthetics is in fine lines, texture and elasticity, and in the area around the eyes.
  • The safety profile described is favourable, with the local discomfort of any injection.
  • They do not replace surgery, or toxin in a movement line, or filler where volume is missing.
  • If you have a fish allergy, say so before treatment: most of these products derive from DNA of fish origin.

Polynucleotides are the injectable most talked about right now, and also the one least written about. They are fragments of purified DNA infiltrated into the skin not to add volume but to act on the quality of the tissue: hydration, elasticity, texture.

The part rarely mentioned is how much evidence lies behind them. When a 2025 systematic review gathered all the literature published over fourteen years on their use in aesthetic medicine, it found nine studies of low and moderate quality, with 219 patients in total. The results point in a good direction. But it is worth knowing what you are leaning on.

If what you want is to restore volume, the standard is hyaluronic acid; if what you want is to generate collagen, compare it with collagen inducers.

What they are and what they are supposed to do

A polynucleotide is a chain of nucleotides: the building blocks of DNA. The products used in aesthetic medicine start from purified DNA — usually of fish origin — fragmented to a given size. Where the fragments are shorter, the term used is usually PDRN, polydeoxyribonucleotides.

When infiltrated into the dermis, the mechanism attributed to them is not occupying space but acting on the environment of the tissue: effects are described on dermal remodelling, on the formation of new blood vessels and an anti-inflammatory action. Hence the stated aim is always the same: better-quality skin, not a face with more volume.

That distinction is the whole page. A patient who comes in asking for polynucleotides because “my under-eye area looks hollow” is in fact asking for something else.

What the evidence says, with the numbers in view

This is the part that decides whether the treatment makes sense for you, so it goes without embellishment.

The 2025 systematic review. It searched Embase, Medline and Cochrane for all primary research published in English between January 2010 and January 2024 on the effectiveness of polynucleotides in aesthetic medicine. It included nine studies, of low and moderate quality, with 219 patients in total. Its conclusions: the injections have shown promising results in reducing wrinkles, improving texture and increasing elasticity, with statistically significant results in several studies; but there is little consensus on their optimal use.

The figure is worth pausing on. Two hundred and nineteen patients is the whole published base a systematic review could gather in fourteen years. It is not a signal that the treatment does not work: it is a signal that it has not yet been studied enough to talk about it with the confidence with which it is promoted.

The comparison with hyaluronic acid. A 2026 review focused on the under-eye area places it precisely: hyaluronic acid remains the reference standard for correcting volume, while polynucleotides show consistent improvements in parameters of dermal quality — elasticity, hydration and fine lines — with a favourable safety profile. The authors also note the limitations of filler in that particular area: its limited effect on skin quality and complications such as the Tyndall effect — the bluish tone of product placed too superficially — or malar oedema. And they close with the same caveat: the heterogeneity of designs, formulations and outcome measures prevents definitive conclusions.

In other words: they do not compete. They solve different things, and the choice depends on what is wrong.

Where they fit

They make sense when the complaint is about skin quality: dull, thin, dehydrated skin with superficial lines and loss of elasticity. And within that, the area around the eyes is where they have been studied most.

They are not the answer in these cases:

  • Volume is missing. A marked fold or an under-eye hollow from loss of support is not corrected with skin quality. That is filler, or it is surgery.
  • It is a movement line. Frown lines, crow’s feet and forehead lines depend on the muscle.
  • There is too much skin. No injectable removes tissue. If the under-eye problem is a bag or there is excess skin, the honest comparison is in blepharoplasty or hyaluronic acid for dark circles.
  • There is an expectation of a visible, immediate change. This is not that kind of treatment.

What it feels like and what risks it carries

It is an injection: it is uncomfortable, and afterwards there may be redness, a temporary weal at the entry points, mild swelling or bruising. It resolves within days.

The safety profile described in the available literature is favourable, and no serious complications attributed to the product appear in it. With one important qualification that applies to all of aesthetic medicine: a 2025 review of adverse effects of facial injectables warns that there is a publication bias in favour of favourable results over adverse effects. When the published base is small, that warning weighs more, not less.

That is why there are two things worth saying before treatment: if you have a fish allergy, because the origin of the product makes it relevant, and if you have any inflammatory condition or active infection in the area.

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Frequently asked questions

Do polynucleotides fill?

No. They add no volume and do not correct a fold. They act on the quality of the tissue. If what is missing is volume, the treatment indicated is a different one.

How many sessions do you need?

There is no established number, and that is precisely one of the conclusions of the systematic review: there is no consensus on optimal use. Several spaced sessions are planned and adjusted according to the response.

When do you notice it?

It is not an immediate result. It is assessed over weeks and on skin parameters — texture, radiance, elasticity — not on a before and after of volume.

Do they work for dark circles?

It depends what kind of dark circle you have. If it is a matter of the quality and thinness of the skin, it is the indication in which they have been studied most. If it is a hollow from loss of support, or a bag, no. Telling them apart is the first step, and it is explained in the comparison on dark circles.

Are they better than hyaluronic acid?

It is not the right question, because they do not do the same thing. The 2026 review sums it up well: hyaluronic acid remains the standard for correcting volume, and polynucleotides show improvements in dermal quality. The choice depends on the problem.

And against collagen inducers?

An inducer aims to generate collagen and provide support, with a more structural and non-reversible effect. A polynucleotide works on the quality of the tissue. They are compared on the inducers page.

Are they safe?

The profile described is favourable and the usual discomfort is local and temporary. That said, the published base is small, so the honest answer is that we do not yet have long-term safety data in large samples.

Can they be combined with other treatments?

It is done in practice. What does not exist is solid evidence supporting any particular combination protocol, so combining should answer a clinical reason in your case and not a fixed package.

Sources

  • Lampridou S, Bassett S, Cavallini M, Christopoulos G. The Effectiveness of Polynucleotides in Esthetic Medicine: A Systematic Review. J Cosmet Dermatol. 2025;24(2). A search of Embase, Medline and Cochrane for primary research published between January 2010 and January 2024; nine studies included, of low and moderate quality, with 219 patients treated; promising results in reducing wrinkles, texture and elasticity, with statistical significance in several studies; the authors conclude that there is little consensus on optimal use. https://pubmed.ncbi.nlm.nih.gov/39645667/
  • Khan RS, Hafeez K. Hyaluronic Acid Fillers Versus Polynucleotides for Under-Eye Rejuvenation. J Clin Med. 2026. Hyaluronic acid remains the reference standard for correcting volume, with limitations in skin quality and complications such as the Tyndall effect and malar oedema; polynucleotides show consistent improvements in elasticity, hydration and fine lines with a favourable safety profile; the heterogeneity of designs, formulations and outcome measures prevents definitive conclusions. https://pubmed.ncbi.nlm.nih.gov/42452433/
  • Di Santis ÉP, Hirata SH, Di Santis GM, Yarak S. Adverse effects of the aesthetic use of botulinum toxin and dermal fillers on the face: a narrative review. An Bras Dermatol. 2025;100(1). It notes a publication bias in favour of successful results over adverse effects and calls for mandatory reporting of the latter. https://pubmed.ncbi.nlm.nih.gov/39616095/

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If you have got this far looking for polynucleotides, the question worth taking to the consultation is not “should I have them?” but “is mine skin quality, volume, muscle or excess skin?”. Only the first is answered by this treatment.

At the assessment we examine the area, explain what is contributing to what you see and tell you what evidence each option has, including this one. If the treatment indicated is a different one, you will be told.

Clinical confirmation by the surgeon

Portrait of Enrique Salmerón González

Dr Enrique Salmerón González

Specialist in Plastic, Aesthetic and Reconstructive Surgery
Registration no. 46/4624077
Portrait of Elena García Vilariño

Dr Elena García Vilariño

Specialist in Plastic, Aesthetic and Reconstructive Surgery
Registration no. 46/4624503

Last reviewed: 23 August 2026. This content is for information only and does not replace an individual assessment by a healthcare professional.

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