Polynucleotides in UK Aesthetic Practice

What Are Polynucleotides?

Polynucleotides (PNs) are chains of nucleotide monomers derived from the selective hydrolysis of DNA extracted from the sperm of salmonid fish, specifically salmon (Oncorhynchus mykissa) and trout. The extraction and purification process yields fragments of varying molecular weight depending on the manufacturing method, ranging from polydeoxyribonucleotide (PDRN) preparations of approximately 0.08 to 1.5 MDa to higher-molecular-weight polynucleotide (PN) fractions used in more recently developed products.

The salmonid source is not arbitrary. Salmonid sperm DNA shares a high degree of nucleotide sequence homology with human DNA (approximately 70 to 80 percent), which is thought to underpin its biological compatibility in human tissue. The purification process removes proteins, lipids, and cellular debris to a purity level that renders the final product non-antigenic in clinical use, consistent with published safety data and the absence of significant immunogenic events in the peer-reviewed literature (Mastelli SPC; Cassuto et al., Journal of Cosmetic Dermatology, 2022).

Mechanism of Action

The biological activity of polynucleotides in tissue is multifactorial, and the relative contribution of each mechanism varies between PDRN and higher-molecular-weight PN fractions.

Fibroblast Stimulation and Matrix Regeneration

The best-characterised mechanism of PDRN/PN action is activation of the adenosine A2A receptor on fibroblasts and other cell types. A2A receptor agonism initiates a downstream signalling cascade that upregulates the synthesis of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF), collectively promoting fibroblast proliferation, migration, and extracellular matrix production including type I and type III collagen (Squadrito et al., Current Vascular Pharmacology, 2014; Park et al., Journal of Cosmetic Dermatology, 2022).

Higher-molecular-weight PN fragments additionally act as a substrate for the salvage pathway of DNA synthesis, providing nucleotide building blocks that cells can incorporate into new DNA during replication. This mechanism, sometimes described as "nutrient salvage", supports the regenerative activity of the product in contexts of cellular stress and hypoxic tissue (Mastelli product documentation and SPC).

Anti-Inflammatory Activity

PDRN and PN preparations consistently demonstrate anti-inflammatory effects in both in vitro and in vivo models. A2A receptor activation inhibits the nuclear factor kappa B (NF-kB) signalling pathway, reducing the transcription of pro-inflammatory cytokines including tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta). This anti-inflammatory activity has been proposed as an additional therapeutic mechanism in conditions characterised by chronic low-grade inflammation, including photodamaged skin and androgenetic alopecia (Gurunluoglu, Annals of Plastic Surgery, 2002; Galeano et al., Journal of Pharmacology and Experimental Therapeutics, 2009).

Angiogenic Support

VEGF upregulation consequent to A2A receptor activation promotes neo-angiogenesis, which supports tissue perfusion and the delivery of oxygen and nutrients to regenerating tissue. This mechanism is particularly well-documented in the wound-healing and reconstructive surgery literature and is thought to contribute to the observed improvement in skin quality and tone following PN treatment courses in aesthetic practice (Altavilla et al., Life Sciences, 2009).

Product Range Available in the UK

Several polynucleotide products are available to licensed practitioners in the UK market. The following overview covers the major lines; practitioners must always consult the current SPC for each specific product before clinical use.

Plinest and Newest (Mastelli S.r.l., Italy)

Plinest and Newest are the market-leading PN products from Mastelli, the Italian manufacturer that originated commercial PDRN/PN development for aesthetic use. Plinest contains 2 mg/ml of highly purified polynucleotides in a physiological solution for intradermal use, indicated for skin bio-regeneration across the face, neck, decolletage, and hands. Newest is formulated with a higher PN concentration (8 mg/ml, also with mannitol for antioxidant stabilisation) and is positioned for more intensive bio-regenerative protocols, including periocular rejuvenation and advanced skin laxity cases.

Clinical data from Mastelli include controlled studies demonstrating improvements in skin elasticity, wrinkle depth, and patient-assessed quality of life at follow-up of three to six months following a standard four-session loading protocol (Mastelli SPC; Cassuto and Bellia, Journal of Cosmetic Dermatology, 2023). The Cassuto and Park publications from 2022 to 2023 represent the most recent peer-reviewed evidence available in English for this product family and are recommended reading for practitioners seeking an independent appraisal of the clinical data.

Nucleofill (Promoitalia Group)

Nucleofill is available in Soft (0.8% PN), Medium (1.5% PN), and Strong (2% PN, with hyaluronic acid) formulations, allowing practitioners to stratify treatment intensity by skin condition, area, and depth of injection. The addition of HA in the Strong formulation positions it at the interface between a pure PN regenerator and a combination skin quality product.

Nucleofill has been the subject of several independent case series and clinical investigations, with publications in the Journal of Cosmetic Dermatology and Aesthetic Medicine supporting improvements in skin firmness, texture, and periocular quality (Promoitalia SPC; peer-reviewed data available via the manufacturer's clinical dossier). The range is manufactured in Italy to CE and UK CA standards.

Aliaxin PN (Professional Dietetics)

Aliaxin PN from Professional Dietetics (the same company behind the Sunekos range) combines polynucleotides with the patented amino acid formulation used in Sunekos, providing a dual-mechanism product targeting both the PN regenerative pathway and the fibroblast amino acid substrate pathway. Available as Aliaxin PN and Aliaxin PN EV (eye-validated formulation for periocular use), the range is positioned for practitioners seeking a combination approach to bio-regeneration.

Published data for Aliaxin PN are primarily from manufacturer-conducted studies and small independent case series. The combination mechanism is theoretically supported by the independent evidence bases for its constituent components, but practitioners should note that the combined product has a more limited independent peer-review record than Plinest or Nucleofill. Consult the Professional Dietetics SPC and current clinical data pack for full prescribing information.

Browse the full polynucleotide range available from Longeva Aesthetics at /collections/polynucleotides.

Clinical Indications

Skin Laxity and Photoageing

The primary aesthetic indication for polynucleotide treatment is skin laxity and photoageing, particularly in areas where the goal is structural skin improvement rather than volumisation. The face, neck, and decolletage are the most commonly treated areas in published clinical series. Peer-reviewed data support improvements in skin firmness, elasticity, and wrinkle depth that are sustained at three to six months follow-up following a standard loading protocol (Park et al., Journal of Cosmetic Dermatology, 2022; Cassuto et al., Journal of Cosmetic Dermatology, 2022).

Polynucleotides are not volumising agents and are not appropriate as a substitute for dermal fillers in patients with significant soft-tissue volume loss. They work best as a complement to volumising procedures or as a standalone treatment in patients with early to moderate skin laxity where quality improvement rather than structural correction is the goal.

Periocular Rejuvenation

The periocular zone is one of the most technically demanding areas in injectable aesthetics, and it is also one where polynucleotides have shown particular clinical utility. The thin, mobile skin of the lower eyelid and periorbital zone responds well to intradermal PN treatment in terms of hydration, skin quality, and the appearance of fine lines, with a risk profile that is more favourable than heavier HA fillers in this area.

Aliaxin PN EV, Nucleofill Soft, and Newest (Mastelli) are all specifically validated for periocular use in their respective clinical dossiers. BCAM and JCCP guidance classifies periocular injectable procedures as advanced-level and requires practitioners to hold appropriate advanced training credentials. This classification applies regardless of whether the product is a filler or a PN regenerator.

Androgenetic Alopecia and Scalp Health

PN-based scalp treatments for androgenetic alopecia represent a growing application area with a credible mechanistic rationale: the combination of fibroblast growth factor upregulation, VEGF-driven angiogenesis, and anti-inflammatory activity addresses several of the proposed pathological mechanisms in androgenetic alopecia. Published data include randomised controlled trial evidence demonstrating improvements in hair density, thickness, and pull-test results compared to placebo over a 12-week injection protocol (Park et al., Dermatologic Therapy, 2019; multiple independent case series in the Korean and Italian literature).

Practitioners should note that scalp PDRN/PN injections are an off-licence use of products whose SPCs primarily describe facial and body skin indications. As with any off-licence use of a licensed medical device, practitioners must be satisfied that the clinical evidence supports the intervention, that the patient has given fully informed consent that includes the off-licence status, and that the procedure is within their training competency.

Patient Selection

Polynucleotide treatments are appropriate for a broad range of patients presenting with concerns related to skin quality, hydration, and fine lines, particularly when the primary goal is regeneration rather than volumisation. Good candidates include the following patient profiles.

Patients with early to moderate facial skin laxity and photodamage who are seeking a non-volumising approach to skin quality improvement.
Patients seeking periocular rejuvenation who are not suitable for or interested in HA filler-based periocular treatment.
Patients with androgenetic alopecia who have been assessed and who understand the off-licence nature of scalp PN treatment.
Patients who have completed a course of structural filler treatment and wish to add a bio-regenerative layer to optimise skin quality.
Patients with fish or seafood allergies are a specific population that requires careful assessment; see the contraindications section below.

PN treatments are not appropriate for patients who require structural volume correction, and practitioners must avoid substituting bio-regenerative products for volumising ones in patients where the underlying deficit is tissue volume loss. Appropriate patient selection is a clinical governance requirement and should be documented in the consultation record.

Contraindications

Fish or seafood allergy: The salmonid DNA source of all current commercial PN products is the primary contraindication that distinguishes this category from HA-based injectables. Patients with a documented allergy to fish or seafood should not receive polynucleotide products. Allergy history must be taken at every consultation and recorded in the patient notes. Practitioners should review the SPC for each product, as allergy exclusion criteria are product-specific.
Known hypersensitivity to any component of the formulation.
Active infection, inflammation, or skin condition at or near the proposed injection site.
Pregnancy and breastfeeding (insufficient safety data; manufacturer SPCs universally contraindicate PN products in these populations).
Active autoimmune disease or conditions treated with immunosuppressive therapy (relative contraindication; assess individually and consult BCAM guidance).
Coagulopathies or current anticoagulant therapy.
Active or recent malignancy (relative contraindication; the pro-proliferative mechanisms of PDRN/PN raise theoretical concerns in the context of active neoplastic disease; practitioners must seek specialist oncological input in any case with a relevant cancer history).
Herpes simplex virus-positive patients: prophylactic antiviral treatment should be discussed and prescribed where the treatment area overlaps with a known HSV distribution, consistent with standard injectable aesthetic practice.

Regulatory Status: MHRA Class III Medical Device and JCCP Register

Polynucleotide injectables for aesthetic use are classified as Class III medical devices in the UK under the Medical Devices Regulations 2002 (as amended), consistent with other injectable aesthetic products. Practitioners and supply-chain managers should verify that any PN product purchased for clinical use carries a valid UK CA mark, is listed on the MHRA Device Registration database, and that the supplier can produce this documentation on request.

The Joint Council for Cosmetic Practitioners (JCCP) does not currently have a separate register category for PN treatments distinct from injectable aesthetics more broadly, but the JCCP's practitioner registration requirements apply to any practitioner administering PN injectables. The JCCP register is referenced by NHS England as a minimum quality marker for aesthetic practice, and practitioners not yet registered are encouraged to engage with the JCCP pathway.

The British College of Aesthetic Medicine (BCAM) has published position statements on bio-regenerative injectables, including polynucleotides, as part of its evidence-based practice framework. These documents provide a practical clinical governance reference and are available to members via the BCAM website (bcam.co.uk).

BCAM Position and Evidence Appraisal

BCAM's position on polynucleotides reflects the broader trajectory of the evidence base: a well-established mechanistic rationale supported by preclinical and early clinical data, a growing body of randomised controlled trial evidence particularly from the Korean and Italian research communities, and a need for further large-scale, multi-centre RCTs to consolidate the evidence base to the standard expected of procedures at this level of clinical adoption.

Practitioners are encouraged to engage with BCAM's educational programme on bio-regenerative injectables, which includes CPD-accredited content covering the PN mechanism, clinical protocols, and the current evidence base. The BCAM position papers are not available for public download and require BCAM membership for access.

Independent peer-reviewed data from Cassuto et al. (2022, 2023) and Park et al. (2022) represent the most clinically useful references for evidence-based practice in this category. Practitioners should read primary sources rather than relying solely on manufacturer-supplied summaries when forming clinical decisions.

See all polynucleotide products and clinical-grade skin regeneration injectables at /collections/all-products. Practitioners planning combination protocols may also wish to review the skin booster range alongside PN options.

Frequently Asked Questions

Why are polynucleotide products derived from salmon or trout DNA?

Salmonid sperm DNA is used because of its high degree of nucleotide sequence homology with human DNA, estimated at approximately 70 to 80 percent. This similarity is thought to underpin the biological compatibility of purified salmonid DNA fragments in human tissue. The purification process removes all proteins, lipids, and cellular debris to render the final product non-antigenic. The salmonid source also provides a consistent, scalable, and regulated raw material supply, which supports manufacturing quality assurance. The specific consequence for clinical practice is that patients with known fish or seafood allergy must not receive PN products and must be screened by full allergy history at every consultation.

How do polynucleotides differ mechanistically from HA skin boosters?

HA skin boosters primarily act by restoring dermal hydration (HA's well-documented water-binding capacity) and, in lower-cross-linked formulations, by stimulating fibroblasts to produce endogenous HA and collagen through the bio-revitalisation mechanism. Polynucleotides work through a distinct pathway: activation of the adenosine A2A receptor on fibroblasts and related cells, which upregulates growth factor synthesis (VEGF, FGF, PDGF) and promotes extracellular matrix production, angiogenesis, and anti-inflammatory signalling. Higher-molecular-weight PN fractions additionally provide nucleotide building blocks for the DNA salvage pathway. The two categories are complementary and are frequently combined in clinical protocols.

Is there randomised controlled trial evidence for polynucleotides in facial aesthetics?

Yes. Randomised controlled trial evidence exists for several polynucleotide products, primarily from Korean and Italian research groups. Park et al. (Journal of Cosmetic Dermatology, 2022) and Cassuto et al. (Journal of Cosmetic Dermatology, 2022 and 2023) are among the most cited recent peer-reviewed sources. Earlier RCT data in wound healing and post-operative recovery contexts provided the mechanistic foundation for aesthetic applications. The overall evidence base is more heterogeneous than that for established HA fillers; practitioners should appraise primary sources directly and refer to BCAM position papers for a synthesised clinical governance framework.

Can polynucleotides be used to treat androgenetic alopecia?

Scalp PN treatment for androgenetic alopecia is an off-licence application with a credible mechanistic rationale and a growing base of published clinical data, including randomised controlled trial evidence (Park et al., Dermatologic Therapy, 2019). The pro-angiogenic, fibroblast-stimulating, and anti-inflammatory mechanisms of PDRN/PN align with proposed pathological drivers of androgenetic alopecia. Practitioners using PN products for scalp indications must ensure full informed consent that explicitly notes the off-licence status, must be satisfied that their training competency covers the scalp as a treatment area, and must document this rationale in the patient record. The primary fish allergy contraindication applies equally to scalp use.

Do I need a different qualification to use polynucleotides compared to HA fillers?

The regulatory framework governing practitioner qualifications for injectable aesthetics in England (CQC licensing, JCCP registration) applies to PN treatments in the same way as to HA fillers. There is no separate qualification category for polynucleotides as a product class. However, specific treatment areas such as the periocular zone and scalp carry the same advanced training requirements regardless of whether the product is a filler or a PN regenerator. Practitioners should ensure their training portfolio covers the specific anatomical areas they intend to treat and that their JCCP registration reflects their current competency scope. BCAM provides CPD-accredited training relevant to bio-regenerative injectables.