The Science Behind Polynucleotide Skin Rejuvenation

Last updated: 9 August 2026

Polynucleotide (PN) therapy represents one of the most exciting developments in regenerative aesthetics. This offers a fundamentally different approach to skin rejuvenation compared to traditional fillers and skin boosters. Derived from purified DNA fragments, most commonly from salmon or trout sperm cells, polynucleotides work at the cellular level to stimulate tissue regeneration, improve skin quality, and promote healing. Practitioners have integrated polynucleotide treatments into our evidence-based skin rejuvenation programmes following the growing body of clinical evidence supporting their efficacy.

What are polynucleotides?

Polynucleotides are long chains of nucleotides, the fundamental building blocks of DNA. When purified and processed for medical use, these biopolymer chains (typically with molecular weights between 50-1,500 kDa) retain their biological activity without containing any genetic information from the source organism. The purification process, which involves multiple stages of extraction, sterilisation, and filtration, produces a biocompatible gel that can be safely injected into human tissue.

Research published in the Journal of Biological Regulators and Homeostatic Agents (Cavallini et al., 2013) demonstrated that polynucleotides are biocompatible, non-immunogenic, and completely resorbable, making them suitable for repeated aesthetic use.

Mechanisms of Action

The biological effects of polynucleotides are multifaceted, operating through several distinct pathways that collectively contribute to tissue regeneration and skin quality improvement:

Fibroblast Stimulation

Polynucleotides bind to purinergic receptors (A2A adenosine receptors) on fibroblast cell surfaces, activating intracellular signalling cascades that promote cell proliferation and increased production of extracellular matrix components including collagen, elastin, and glycosaminoglycans. In vitro studies by Toriumi et al. (2012) showed that PN-treated fibroblasts demonstrated a 2-3 fold increase in proliferative activity compared to untreated controls.

Anti-inflammatory effects

Polynucleotides modulate the inflammatory response by scavenging free radicals and reducing the production of pro-inflammatory cytokines. This anti-inflammatory action is particularly valuable in treating conditions characterised by chronic low-grade inflammation, including photoaged skin and rosacea-prone skin types.

Hydration and tissue scaffolding

PN gels have significant water-binding capacity. This provides immediate hydration to treated tissues. Also, the polymer chains create a temporary scaffolding structure that supports tissue organisation during the regenerative process.

Angiogenesis Promotion

Polynucleotides stimulate the formation of new blood vessels (angiogenesis) through upregulation of vascular endothelial growth factor (VEGF). This improved blood supply enhances oxygen and nutrient delivery to treated skin, supporting healthier tissue function and improved skin vitality.

Clinical Evidence

The evidence base for polynucleotide treatments in aesthetic medicine has expanded significantly in recent years:

• A randomised controlled trial by Cavallini et al. (2021) published in the Journal of Cosmetic Dermatology demonstrated statistically significant improvements in skin elasticity, hydration, and wrinkle depth following a course of three PN treatments at monthly intervals
• Histological analysis by De Caridi et al. (2016) confirmed increased collagen deposition and improved dermal thickness in PN-treated tissue biopsies
• Comparative studies have shown that polynucleotides produce superior improvements in skin elasticity compared to hyaluronic acid skin boosters alone

Treatment areas and applications

Polynucleotide treatments are versatile and can be applied to multiple areas of concern:

• Faceoverall skin quality improvement, fine lines, and photoageing
• Periorbital areaunder-eye dark circles, crepey skin, and fine lines (an area where traditional fillers carry higher risks)
• Neck and décolletagecrepey skin and horizontal necklines
• Handsvolume loss and skin thinning
• Scalphair restoration (emerging evidence for improved follicular health)
• Acne scarringtissue regeneration in scarred skin

The treatment protocol

A standard polynucleotide treatment course typically involves 2-4 sessions spaced 2-4 weeks apart, with maintenance treatments every 4-6 months. The product is administered via multiple intradermal microinjections using either a needle or cannula technique, depending on the treatment area and practitioner preference.

The treatment is generally well tolerated, with most patients reporting only mild discomfort. Topical anaesthesia can be applied prior to treatment for sensitive patients or sensitive areas such as the periorbital region. Post-treatment, patients may experience mild redness, swelling, and small injection-point marks that typically resolve within 24-48 hours.

Polynucleotides vs other skin boosters

Whilst hyaluronic acid skin boosters primarily work through hydration and superficial volumisation, polynucleotides offer a fundamentally regenerative approach. The two treatments are complementary rather than competing, many advanced protocols combine PN therapy with HA skin boosters or Profhilo to address both hydration and cellular regeneration simultaneously. This combination approach is supported by growing clinical consensus among aesthetic medicine specialists.

Frequently asked questions

Are polynucleotide treatments safe?

Yes, polynucleotide treatments have an excellent safety profile. The products are derived from highly purified DNA fragments that are biocompatible and non-immunogenic. They do not contain genetic information from the source organism. Published clinical studies report very low rates of adverse events, with most side effects being mild and temporary.

How soon will I see results from polynucleotide treatment?

Some patients notice an immediate improvement in skin hydration and luminosity. However, the regenerative effects, improved elasticity, reduced fine lines, and enhanced skin quality, develop progressively over 4-8 weeks as new collagen and elastin are produced. Optimal results are typically seen 2-3 months after completing a treatment course.

Can polynucleotides be used around the eyes?

Yes, the periorbital area is one of the most popular treatment zones for polynucleotides. Because PNs work through biostimulation rather than volumisation, they are safer than traditional fillers in this delicate area and can effectively improve dark circles, crepey skin, and fine lines around the eyes.

What is the difference between polynucleotides and Profhilo?

Profhilo is a hyaluronic acid-based skin booster that works primarily through deep hydration and HA-mediated bioremodelling. Polynucleotides work through DNA fragment-mediated fibroblast stimulation. This offers a regenerative mechanism. Both improve skin quality but through different biological pathways, and they can be used in combination for enhanced results.