The Ultimate Guide to Polynucleotides: What are Polynucleotides?

I get asked this more than almost any other question in clinic.

A patient walks in having done her research, seen both polynucleotides and Profhilo mentioned online, and sits down and says: "I know I need something regenerative. But I have no idea which one to choose."

It is a genuinely good question. And it deserves a proper answer, not a summary table and a booking link. The difference between these treatments is not just a difference in ingredients. It is a difference in biology, mechanism, timeline, and the type of skin problem each one is designed to solve.

This guide covers what polynucleotides actually are, what is happening in your skin after treatment, the three mechanisms most clinics do not explain, how they compare to Profhilo, and how to decide which conversation you should be having.

What polynucleotides actually are

Polynucleotides, also called PDRN or polydeoxyribonucleotides, are long-chain DNA fragments extracted and purified from salmon sperm cells. I know that sentence sometimes produces a reaction in the consultation room. Let me explain why it should not.

Salmon DNA shares a remarkably high structural similarity with human DNA. The fragments used in treatment are not cells, not organisms, nothing biologically active in their own right once extracted. They are purified nucleotide chains that our own cellular machinery recognises and processes as if they were endogenous. The purification process removes proteins entirely, which is why adverse reactions are rare to the point of being clinically unusual.

This is not a new treatment. PDRN received pharmaceutical approval in Italy in 1994 for wound healing, skin ulcers, and connective tissue disorders. Before a single aesthetic clinic offered it, it had spent thirty years in wound wards and diabetic ulcer treatment, building a clinical evidence base that most aesthetic treatments will never accumulate. In cardiac nursing, I spent years in clinical environments where wound healing science was applied medicine, not background reading. That heritage is part of why polynucleotides earned my confidence before they became fashionable.

The critical distinction from almost every other injectable is this. Polynucleotides do not add volume. They do not fill space. They do not freeze muscle activity or create an injury response. Instead, they communicate directly with the cells in your dermis, triggering a biological cascade that instructs those cells to behave as they did when you were younger. This is molecular signalling. Not filler. Not damage repair. Something categorically different.

What is actually happening in your skin

The biological timeline of polynucleotide treatment is the part of consultations patients find most engaging, possibly because I cannot help becoming genuinely animated when I explain it.

In the first hours after injection, the polynucleotide gel disperses through the dermis. Small raised blebs appear at the injection points. These are a distribution pattern, the product settling into tissue planes. There is no aesthetic change yet and there should not be. This treatment asks you to wait, and the waiting is doing something important.

Over the first week, your own endogenous DNase enzymes begin breaking the long polynucleotide chains into smaller active fragments. This is the part most practitioners do not explain clearly enough. The breakdown is not the treatment wearing off. It is the treatment beginning.

Those fragments bind to adenosine A2A receptors on the surface of fibroblasts, the cells responsible for producing your skin's structural proteins. A 2025 comparative review published in PMC confirms that PDRN selectively activates this A2A receptor, modulating inflammation, stimulating angiogenesis, and enhancing collagen production in dermal fibroblasts. A2A receptor activation triggers a coordinated cascade: collagen production increases, new elastin forms, hyaluronic acid is generated naturally within the extracellular matrix, and pro-inflammatory cytokines are suppressed.

The collagen produced through this pathway is organised and structurally sound, equivalent to what a healthy dermis generates naturally. This distinguishes it from injury-based collagen treatments. Radiofrequency, lasers, and chemical peels work by creating controlled tissue damage. The body produces collagen as part of a wound-healing response. That collagen is functionally adequate but disorganised. Polynucleotides bypass injury entirely. The fibroblasts are being signalled to do their job properly, not compensating for damage.

Three effects most clinics do not explain

Beyond the collagen stimulation, there are three specific mechanisms that place polynucleotides in a category nothing else currently occupies.

Senescent fibroblast reactivation

As skin ages, fibroblasts do not simply disappear. They enter a state of cellular retirement where they stop responding to normal signals and contribute nothing to collagen production. They are still present in the dermis. They are simply no longer participating. Research published in PLOS ONE demonstrated that PDRN treatment restores activity in these dormant cells, particularly in skin that has experienced UV damage and oxidative stress, with effects especially consistent in donors over sixty. Polynucleotides are not just stimulating fibroblasts that are already working. They are calling back the ones that have stopped.

UV damage repair at the molecular level

The salvage pathway activated alongside the A2A receptor supports repair of cyclobutane pyrimidine dimers: the specific DNA lesions created by UVB radiation. For patients with accumulated sun exposure, polynucleotides are not treating the surface appearance of that damage. They are intervening at the molecular level where the damage itself lives.

Anti-inflammaging effect

Chronic low-grade inflammation, what longevity researchers now call inflammaging, is one of the primary drivers of accelerated skin ageing. It degrades collagen faster than it can be replaced, impairs fibroblast function, and creates a tissue environment that resists repair. Polynucleotides actively suppress the pro-inflammatory cytokines that sustain this process. The treatment is not only addressing the skin you have today. It is changing the biological conditions in which that skin will continue to age.

What Profhilo actually is and how it differs

Profhilo is an injectable skin booster composed of ultra-pure hyaluronic acid, stabilised using a patented technology called NAHYCO that combines high and low molecular weight HA without chemical cross-linking agents. With 64mg of hyaluronic acid per 2ml, it is one of the highest concentrations available in aesthetic medicine.

The key distinction from conventional filler is that Profhilo does not stay put. Once injected, it spreads through the tissue in all directions, delivering deep hydration to a large area of dermis simultaneously. Rather than sitting in a specific location and adding structure, it diffuses broadly, improving the tissue environment in which cells are operating. It is administered via five BAP injection points per side: the zygomatic protrusion, nasal base, lower cheek, jawline, and chin.

From my cardiac nursing background, I think of Profhilo as working at the tissue environment level. It improves the conditions around the cells, hydrating the extracellular matrix, creating the right biochemical environment for the skin to function better and rebuild more effectively. Polynucleotides work at the cellular signal level: they reach into the fibroblast and change its instructions directly.

What I tell patients when they ask which one to choose

Profhilo is the treatment I usually suggest for patients new to regenerative aesthetics, whose primary concern is dehydration and early quality loss, and who want to understand what working with the skin's own biology actually produces before committing to a longer biological timeline. The early glow is noticeable and reassuring. The collagen stimulation builds progressively behind it.

Polynucleotides are the treatment I reach for when the primary issue is more than hydration: accumulated UV damage, collagen decline at a stage where we need to reactivate dormant fibroblasts, persistent inflammaging driving quality loss that does not fully respond to hydration-based treatment, or patients in their fifties and beyond whose skin is not responding as expected to what should be working. The mechanism goes deeper and the timeline is longer, but for the right patient it produces a quality shift that nothing else currently replicates.

Most patients benefit from both. They are not competing treatments. They address different layers of the same problem. The approach I use most often is Profhilo as the entry point, establishing the tissue environment and giving the patient a tangible early result, followed by polynucleotides to address the cellular regeneration that Profhilo supports but does not directly drive. In a phased protocol over six to twelve months, the combination produces outcomes noticeably better than either alone.

Results: what to expect and when

A patient I treated with significant photoageing described her results at twelve weeks in a way that has stayed with me. She said her skin looked like it had remembered something. That is a more precise description of the mechanism than most clinical language manages.

The improvement is gradual and cumulative. In the first two to four weeks, most patients notice their skin feels different before it looks different: better hydrated, slightly more responsive, less flat. Between weeks four and eight, texture improves and the beginnings of firming become visible. By weeks eight to twelve, the remodelling is at its most active. Skin looks healthier, more even, more luminous. The most consistent thing patients tell me is that people around them have started commenting they look well, without being able to say what has changed. That is the result working as intended.

Frequently asked questions

Are polynucleotides the same as salmon DNA injections?

Yes, the same treatment described differently. The salmon DNA is purified to remove all biological material except the nucleotide chains themselves, producing a clear sterile injectable solution with nothing cellular remaining.

Can I have polynucleotides and Profhilo at the same session?

Yes. They work through different mechanisms and can be delivered in the same appointment. Sequencing depends on areas being treated and is discussed at consultation.

How many sessions do I need?

Two sessions four weeks apart for an initial course. Maintenance one session every six to twelve months. Some patients with more significant photoageing benefit from a third session in the initial course.

Will I see results immediately?

No. The mechanism is biological and unfolds over weeks. Most patients notice their skin feels different before it looks different, with visible improvement building from around weeks four to eight.

Is there anyone who should not have polynucleotides?

Patients with a fish allergy should not receive salmon-derived polynucleotides. Pregnancy and breastfeeding are contraindications. Active skin infection in the treatment area is a contraindication. A full medical history is taken before every treatment.

We see patients from across Kent including Maidstone, Tonbridge, Sevenoaks, Kings Hill, West Malling, Medway, and Chatham.

References

1. Comparative review of PDRN and PN mechanisms — PMC: pmc.ncbi.nlm.nih.gov/articles/PMC12388916

2. A2A receptor activation, fibroblast differentiation and VEGF upregulation — PMC: pmc.ncbi.nlm.nih.gov/articles/PMC8618295

3. Systematic review: polynucleotide injections in skin rejuvenation — Journal of Cosmetic Dermatology: onlinelibrary.wiley.com/journal/14732165

4. PDRN and cellular senescence mitigation — PLOS ONE: journals.plos.org/plosone/article?id=10.1371/journal.pone.0321005

5. Comparative review of PDRN and PN: A2A receptor activation, mechanisms and clinical applications — PMC, 2025

6. A2A receptor activation, fibroblast differentiation, and VEGF upregulation — PMC

7. PDRN mitigates cellular senescence from UVB and oxidative stress — PLOS ONE

8. Polynucleotide injections for skin rejuvenation: systematic review — Journal of Cosmetic Dermatology

9. Polynucleotide injections for periorbital rejuvenation — PMC