What Polynucleotides Are and Their Source
Polynucleotides skin treatments represent one of the more discussed categories in UK aesthetics at present, yet the underlying science remains less familiar to many practitioners than that of hyaluronic acid products. A clear understanding of what these molecules are is the appropriate starting point.
Polynucleotides are long chains of nucleotide units. Nucleotides are the structural components of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). In the context of aesthetic medicine, the polynucleotides of primary clinical interest are polydeoxyribonucleotides (PDRN), which are highly purified fragments of salmon or trout DNA. Salmon-derived PDRN has been the most extensively studied in the peer-reviewed literature, with a body of research accumulated largely in wound healing, tissue repair and anti-inflammatory contexts before migrating into aesthetic applications.
The manufacturing process is critical to safety. Raw material from salmon (Oncorhynchus mykiss or Oncorhynchus keta) undergoes multi-stage purification to remove all proteins, lipids and non-nucleotide biological material, yielding isolated DNA fragments in a defined molecular weight range. Manufacturers of medical-grade products are required to document this process and demonstrate freedom from immunogenic contaminants, as described in published literature indexed on PubMed Central.
More recently, polynucleotide formulations derived from plant sources have entered the market. The evidence base for these is considerably less developed than that for PDRN, and practitioners should scrutinise the available data carefully before treating them as equivalent.
The Proposed Mechanism: Fibroblast Activity and Tissue Conditioning
The polynucleotide mechanism of action is proposed to operate through two primary pathways, both of which are described in published scientific literature, though it is important to characterise the current state of evidence accurately rather than overstating what is established.
The first and most extensively investigated pathway involves the activation of adenosine A2A receptors. PDRN is degraded extracellularly into its component nucleosides, one of which is deoxyadenosine. Deoxyadenosine, and adenosine derived from it, can bind to adenosine A2A receptors on cell surfaces. A2A receptor activation has been associated in published research with a range of downstream effects including increased production of vascular endothelial growth factor (VEGF), reduction in pro-inflammatory cytokines, and stimulation of fibroblast proliferation and activity. Studies demonstrating these effects in vitro and in animal models are summarised in reviews published in journals including the European Journal of Pharmacology and are indexed on PubMed Central.
The second proposed pathway is the direct salvage of nucleotide building material by cells undergoing repair, via the nucleotide salvage pathway. This is more speculative, and the in vivo evidence in human aesthetic applications remains limited.
In the context of skin aesthetics, the clinical outcome described in published studies includes improvements in skin hydration, elasticity and tissue quality, as well as acceleration of repair in compromised skin. Research published in peer-reviewed journals, including studies cited in the manufacturer documentation for products such as Placentex (PDRN, Mastelli) and Rejuran (PN, Pharmos Biopharma), has reported improvements in skin laxity and texture scores in randomised and observational study designs. However, the total volume of high-quality randomised controlled trial evidence remains limited compared to the hyaluronic acid filler literature, and practitioners should maintain appropriate epistemic caution.
How Polynucleotide Approaches Differ from Profhilo
A common question in clinical practice is how to position polynucleotides vs Profhilo, and whether one should be preferred over the other. The answer requires understanding the mechanistic distinction clearly.
Profhilo's primary mechanism is the direct effect of high-concentration hyaluronic acid on tissue hydration and on receptors (principally CD44) that trigger fibroblast activity and collagen synthesis. The product provides an immediate and substantial hydration effect, and its tissue-remodelling properties derive from receptor-mediated signalling. The manufacturer Summary of Product Characteristics and associated clinical literature describe this in detail.
Polynucleotides act through an entirely different molecular pathway (adenosine receptor signalling and nucleotide salvage) and do not provide the same immediate hydration effect. PDRN is not a hydrating agent in the same sense as hyaluronic acid; its proposed clinical value lies in tissue conditioning, fibroblast stimulation and the support of repair processes rather than direct moisture retention.
In practical terms, this means the two approaches may address different aspects of skin ageing or damage, and there is a clinical rationale for using them in combination or in sequence. Profhilo may be more appropriate where the primary concern is hydration, skin laxity and collagen stimulation via the hyaluronic acid pathway. Polynucleotides may offer an adjunct or alternative where the goal is tissue repair, recovery from environmental damage, or support of regenerative processes. Whether this rationale translates to measurably superior outcomes in combination is not yet established by high-quality randomised evidence.
Delivery via Mesotherapy: A Conceptual Overview
Many polynucleotide products are delivered using a mesotherapy approach. Mesotherapy, as a concept, refers to the intradermal or shallow subdermal delivery of active substances through multiple injections distributed across a treatment area. The technique is designed to place the active ingredient close to the target tissue (the dermis and the fibroblasts within it) rather than depositing material in a discrete bolus.
Widespread intradermal distribution allows the active PDRN or PN fraction to interact with fibroblasts and other target cells across the treatment area, consistent with the diffuse tissue-conditioning intent of the therapy rather than the localised volumisation goal of a conventional filler.
Specific injection techniques, depths, and protocols are outside the scope of this article and should be addressed through certified training from a recognised aesthetics education provider. Practitioners should hold appropriate qualifications and indemnity for any injectable procedure undertaken, in accordance with guidance published by the JCCP and Health Education England's framework for non-surgical aesthetics.
Regulatory and Quality Considerations When Sourcing in the UK
Sourcing polynucleotide products appropriately is one of the most important considerations for UK practitioners, and the regulatory landscape requires careful attention.
Injectable polynucleotide products used in aesthetic practice are regulated as medical devices in the UK. Following the end of the Brexit transition period, the UK has moved towards UKCA marking as the conformity assessment route for medical devices placed on the Great Britain market, administered by the MHRA. CE-marked products (under EU MDR or the predecessor MDD) continue to be accepted in Great Britain during a transition period, the details of which practitioners should verify directly with the MHRA, as the timeline has been subject to revision. Products placed on the Northern Ireland market remain subject to EU rules under the Windsor Framework.
Practitioners should verify that any polynucleotide product they source carries the appropriate conformity marking for the UK market, that the indication for aesthetic use is within the product's licensed scope, and that the product is supplied by a licensed wholesale dealer holding a valid Wholesale Dealer's Authorisation (WDA) from the MHRA. Sourcing injectable products outside licensed supply chains is a regulatory and patient safety risk.
Provenance is particularly important for biological-origin products such as PDRN. Key quality indicators include the manufacturer's country of origin, evidence of GMP (Good Manufacturing Practice) certification as defined by the MHRA and European Medicines Agency, confirmed purification processes, and lot-by-lot batch testing documentation. Reputable manufacturers will supply a Certificate of Analysis for each product lot.
Practitioners should also note that having a published evidence base for PDRN as a molecular class does not automatically validate every product marketed under a polynucleotide or PN label. Evidence should be evaluated at the level of the specific licensed product. As UK aesthetics licensing requirements continue to develop under the Health and Care Act 2022, staying current with JCCP guidance and MHRA communications is an ongoing professional obligation.
Frequently Asked Questions
What are polynucleotides and where do they come from?
Polynucleotides are chains of nucleotide units, the building blocks of DNA, extracted and purified from salmon or trout sperm (polydeoxyribonucleotide, PDRN) or, in some formulations, from plant sources. Medical-grade products use highly purified, isolated DNA fragments that are free from proteins and other biological material. The extraction and purification process is described in manufacturer documentation and peer-reviewed literature published in journals indexed on PubMed Central.
How do polynucleotides differ from Profhilo?
Profhilo is a hyaluronic acid bio-remodelling product that works primarily through direct hydration and the stimulation of collagen and elastin synthesis via hyaluronic acid receptor engagement. Polynucleotides are DNA fragments that are proposed to act via a different pathway: activation of adenosine A2A receptors and direct provision of nucleotide building material to cells. The two approaches may be complementary, but they are mechanistically distinct and should not be conflated.
Is the evidence for polynucleotides strong?
The evidence base for PDRN (polydeoxyribonucleotide), the most studied polynucleotide fraction, includes a number of randomised controlled trials and published case series, particularly in wound healing and tissue repair contexts. The aesthetic application evidence is growing but less mature than that for hyaluronic acid fillers. Practitioners should review manufacturer-cited studies and seek independently published peer-reviewed data, particularly studies indexed on PubMed Central, before drawing conclusions about clinical outcomes.
What should I look for when sourcing polynucleotide products in the UK?
Polynucleotide injectable products used in aesthetics should carry appropriate UKCA or CE marking under the relevant Medical Devices Regulations framework. Practitioners should source from licensed wholesale dealers holding a Wholesale Dealer's Authorisation (WDA) issued by the MHRA. Provenance, including the manufacturer's country of origin, GMP (Good Manufacturing Practice) certification and batch traceability, should be verifiable. Products from unverified sources carry unquantifiable safety risks.
Can polynucleotides be delivered via mesotherapy?
Mesotherapy refers to the intradermal or subdermal delivery of active substances using multiple superficial injections. Some polynucleotide products are formulated and licensed for delivery via this approach. Practitioners should confirm that the specific product they are using is licensed for the intended delivery method, as described in the manufacturer Summary of Product Characteristics, and should have received appropriate training for the technique being used.