Polynucleotides — A Clinician's Honest and Cautious Assessment
When a new treatment arrives trailing social media excitement and bold claims, the temptation is to dismiss it. I nearly did. Here is what the science says, what my early clinical experience suggests, and why the most important question about polynucleotides remains, for now, unanswered.
The problem with arriving at the right time
Polynucleotides arrived in UK aesthetic practice accompanied by the kind of enthusiasm that should, by now, make any experienced clinician reach instinctively for their scepticism. Social media was confident. The claims were bold. Every new treatment in aesthetic medicine seems to arrive as a revolution, and most of them turn out to be considerably more modest in clinical practice than their launch suggested.
I started using polynucleotides with precisely that scepticism intact. Almost hoping, if I am honest, to confirm what I suspected; that this was another treatment whose promise would not survive contact with real patients. The early results gave me pause. They were better than I expected. But I am not yet ready to set my scepticism down entirely, and I think the reasons why are worth examining carefully.
What polynucleotides actually are
Polynucleotides (PN) and their closely related form, polydeoxyribonucleotides (PDRN), are purified DNA fragments derived predominantly from salmon sperm; a source that raises eyebrows in the consulting room but is biocompatible with human tissue due to the structural similarity between salmon and human DNA. When introduced intradermally, they do not fill or volumise in the conventional sense. They initiate a biological response at the cellular level. The proposed mechanism of action involves the formation of a hydrophilic, scaffold-like matrix that supports tissue remodelling and hydration.
The primary molecular mechanism is well characterised in the literature. The mechanism of action of PDRN primarily involves the selective activation of adenosine A2A receptors, alongside complementary salvage pathways. Through these processes, PDRN facilitates collagen synthesis, promotes fibroblast proliferation, encourages angiogenesis, aids in DNA repair, and modulates inflammatory mediators Charismabeautylounge This is a genuinely distinct mechanism from the biostimulators we discussed in earlier pieces in this series. Sculptra works through a foreign body response; polynucleotides work through receptor-mediated cellular signalling. The distinction matters both scientifically and clinically.
What the evidence base currently shows
The research into polynucleotides in aesthetic medicine is growing rapidly, though it remains at an earlier stage of development than the evidence base for established biostimulators like PLLA. A systematic review of three major databases found that polynucleotides offer promising potential in aesthetic medicine; however, there is limited consensus regarding their optimal use, and rigorous, high-quality studies are essential to validate their effectiveness and safety. Polynucleotidestherapy
What the existing literature does support, with reasonable consistency, is an improvement in skin hydration, texture, elasticity, and overall dermal quality following a course of treatment. Polynucleotides have demonstrated notable efficacy in enhancing skin hydration, elasticity, and overall dermal health, primarily through mechanisms that promote cellular repair and collagen synthesis. London Dermatology Centre The periorbital area, under-eye hollowing, and generalised skin quality improvement appear to be the indications with the strongest evidence base at this stage.
My early clinical observations
The patients I have treated with polynucleotides to date have, in the majority of cases, shown an encouraging early improvement in skin quality. The changes texture and fine lines in have been noticeable, and in some cases more marked than I anticipated. Whether this reflects genuine new collagen formation, improved hydration through the scaffold mechanism, or a combination of both is not always clear from clinical observation alone. The mechanism, as described in the literature, would suggest that both are contributing.
What I have not yet been able to assess with confidence is the durability of those improvements. This is the question I keep returning to, and it is the one the literature addresses least satisfactorily. Most published data on longevity is derived from manufacturer-funded studies or clinic-based observational reports. Polynucleotide results typically last six to nine months after completing a full course of two to three sessions, with the collagen and elastin produced during treatment persisting as real structural proteins in the tissue. That is the consensus figure circulating in the clinical community. Whether it holds across a broader patient population, across different product formulations, and across repeated treatment cycles is not yet established to my satisfaction.
The durability question — why it matters
The distinction between early improvement and durable improvement is not academic. Aesthetic medicine has a long history of treatments that produce impressive initial results but prove less compelling on longer follow-up. The question I am most interested in, after two to three treatment sessions, is not whether the skin looks better immediately afterwards. It is whether that improvement persists meaningfully at six months, and whether repeated treatment cycles produce a cumulative benefit that justifies the ongoing investment.
The theoretical basis for cumulative benefit is sound. Patients who complete multiple courses over time typically find that each course builds on the previous one, producing a cumulatively higher baseline of skin quality, with the duration between maintenance sessions potentially extending as the structural foundation in the skin strengthens. PubMed That is a plausible and encouraging hypothesis. It is not yet, in my view, sufficiently supported by independent long-term clinical data to be stated as established fact.
Where the jury remains out
I want to be clear about what I am and am not saying. I am not dismissing polynucleotides. The science is credible, the mechanism is genuinely interesting, and my early clinical experience is encouraging.
What I am saying is that the field is in an early phase of understanding, that the most important questions about durability and cumulative benefit are not yet answered to the standard I would prefer, and that the enthusiasm with which this treatment has been promoted has, in places, run considerably ahead of the evidence.
That is a familiar story in aesthetic medicine. It does not make the treatment without merit. It makes careful, critical clinical engagement more important than ever. I will continue using polynucleotides, continue observing outcomes, and continue asking the durability question. When I have a better answer, I will say so in these pages.
A note on product variation
One further complexity worth acknowledging is the significant variation between polynucleotide products currently available. Molecular weight, purification method, concentration, and formulation all differ between brands, and these differences are likely to have clinically meaningful effects on both efficacy and durability. The research landscape has not yet adequately addressed product-specific outcomes, which means that results reported for one formulation cannot be assumed to apply to another. This is an area where clinical experience, combined with a close reading of the emerging literature, is the best guide available.
The views expressed in Clinical Perspectives are the author's own and reflect their personal and professional experience in aesthetic medicine. This piece will be updated as the evidence base develops.
References
Kim ST. Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives. Pharmaceutics. 2025;17:1024. https://pmc.ncbi.nlm.nih.gov/articles/PMC12388916/
Lampridou S et al. The Effectiveness of Polynucleotides in Esthetic Medicine: A Systematic Review. Journal of Cosmetic Dermatology. 2025. https://onlinelibrary.wiley.com/doi/10.1111/jocd.16721
Lee KWA et al. Polynucleotides in Aesthetic Medicine: A Review of Current Practices and Perceived Effectiveness. International Journal of Molecular Sciences. 2024;25:8224. https://www.researchgate.net/publication/382724822
Titcomb L. A literature review on polynucleotide efficacy on skin rejuvenation, and review of the regulatory status and guidelines around polynucleotides. Journal of Aesthetic Nursing. 2025;14:98–126. https://www.aestheticnursing.co.uk/content/clinical/a-literature-review-on-polynucleotide-efficacy
Expert Perspectives: Evidence-Based Applications of Polynucleotides in Aesthetic Medicine and Dermatology. Clinical, Cosmetic and Investigational Dermatology. 2026. https://www.tandfonline.com/doi/full/10.2147/CCID.S557226
Silva SJ, Cé R. Therapeutic Potential of Polydeoxyribonucleotide (PDRN) in Dermatology and Aesthetic Medicine. Global Journal of Pharmacy and Pharmaceutical Sciences. 2025;12(2). https://juniperpublishers.com/gjpps/pdf/GJPPS.MS.ID.555832.pdf