Polynucleotides and PDRN: what they are, what they treat, and how they compare to HA fillers

Polynucleotides (PN) and polydeoxyribonucleotide (PDRN) treatments are among the fastest-growing segments of aesthetic medicine — and among the least understood by patients who encounter the marketing. Here's what the science actually shows.

What polynucleotides are

Polynucleotides are chains of nucleotides — the building blocks of DNA and RNA. In aesthetic medicine, they're derived from salmon or trout sperm DNA, which has a high degree of homology with human DNA (similarity in base pair sequence). After extraction and purification, the DNA is fragmented into chains of varying lengths.

Two related terms:
PDRN (polydeoxyribonucleotide): Shorter DNA fragments; historically the term used in wound healing and regenerative medicine research
PN (polynucleotides): Longer chain fragments; now the predominant term in aesthetic injectable products

In practice, many products are marketed interchangeably; the distinction matters more in clinical research than in typical aesthetic use.

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Mechanism of action

Polynucleotides work through two primary pathways:

Receptor-mediated signaling (A2A receptor agonism): PN fragments activate adenosine A2A receptors, which:
Stimulate fibroblast proliferation and activity
Upregulate collagen (Type I and III) and elastin synthesis
Reduce inflammatory cytokine activity (anti-inflammatory effect)
Support tissue repair and remodeling

Nucleotide salvage pathway: The degraded PN fragments are taken up by cells and used as building blocks for new DNA synthesis — directly supporting cell proliferation and tissue regeneration.

Key difference from HA: Hyaluronic acid skin boosters (Profhilo, Restylane Skinboosters, Belotero Revive) work primarily by adding hydration, attracting water to the dermis, and providing a mild physical scaffold. PN treatments work primarily through biological signaling — they stimulate the tissue to regenerate, rather than adding a molecule that provides hydration directly.

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Main products on the market

Rejuran (Rejuran Healer, Rejuran S, Rejuran I)
Origin: South Korean; dominant in East Asia, growing in Europe and UK
Active: PDRN/PN derived from salmon DNA
Variants: Original Rejuran Healer (face skin regeneration), Rejuran S (higher viscosity for scars), Rejuran I (periorbital/eye area)
Evidence: Multiple Korean clinical trials showing improved skin texture, elasticity, hydration, and fine line reduction at 12–24 weeks

Jalupro (Classic, HMW, Superhydro)
Origin: Italian
Active: Amino acid complex (glycine, L-proline, L-leucine, L-lysine) + HA in some formulations; the amino acids support collagen synthesis
Note: Jalupro Classic is amino acids without PN; Jalupro HMW adds hyaluronic acid. Technically not a pure PN product — included here because it's often marketed alongside PN products for similar indications
Use: Skin biorevitalization — improving texture, hydration, mild skin quality improvement

Nucleofill (Strong, Medium, Soft)
Origin: Italian
Active: PN from salmon DNA
Variants: Different molecular weights for different depths/applications (strong for dermis, soft for periorbital/hands)
**Growing presence in Europe and the UK

Plinest / Newest (Mastelli)
Origin: Italian
Active: PN, PDRN mix
Used in both aesthetic medicine and wound healing contexts

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What PN/PDRN treats

The most evidence-supported applications:

Skin quality and texture: Multiple controlled trials show improvement in skin elasticity, smoothness, and hydration over a 3–4 session protocol. The effect accumulates over 8–12 weeks.

Fine lines: Particularly periorbital (around the eyes) and thin-skin areas. The skin regeneration mechanism is well-suited to delicate areas where more aggressive treatments carry higher risk.

Skin laxity (mild): Fibroblast stimulation and collagen synthesis improve skin firmness over time. Not a substitute for structural treatment of significant laxity.

Post-acne skin quality: The anti-inflammatory and collagen-stimulating properties make PN relevant for post-acne skin that has texture irregularities, enlarged pores, and mild scarring.

Post-procedure skin recovery: Some protocols use PN after laser or microneedling to support the healing response and amplify collagen stimulation.

Under-eye area (Rejuran I): One of the specific formulations designed for periorbital skin thinning, crepiness, and fine lines under the eye — an area where many other treatments are too risky or too aggressive.

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Clinical evidence summary

The evidence base is growing but has limitations:

Strongest evidence: Korean trials on Rejuran with objective skin parameter measurements (Cutometer, Tewameter, Visioface) showing improvements in elasticity, hydration, and smoothness. Generally small sample sizes (20–60 patients) but consistent positive findings.

Honest assessment: The evidence is positive and consistent enough to make PN treatments a credible option — but the evidence base is not as extensive or rigorously powered as, say, the PREEMPT trials for Botox or the major HA filler trials. Most studies are single-arm or small RCTs; long-term durability data beyond 6 months is limited.

Comparison to HA boosters: Head-to-head data is limited. In practice, PN and HA boosters are often used together for complementary effects: PN for biological regeneration, HA for immediate hydration boost.

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Protocol

Standard course: 3–4 sessions, 2–4 weeks apart

Technique: Superficial intradermal injection (skin-whealing technique) — very small volumes distributed across the treatment area using multiple microinjection points. No deep injection needed; the target is the dermis.

Areas treated: Face (full or specific zones), neck, décolletage, hands, periorbital, perioral

Onset: Skin quality improvement begins building after session 2; full effect assessed at 4–8 weeks after completing the course

Duration: 6–12 months before a maintenance session; varies by patient

Downtime: Minimal. Small bumps (wheals) resolve within hours. Mild redness for 1–4 hours. Most patients return to normal activity the same day.

Pain level: Moderate — multiple intradermal injections sting. Topical anesthetic cream beforehand is standard.

Cost: $250–$600 per session; $800–$2,000 for a complete course

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PN vs HA skin boosters: choosing between them

| Factor | PN / PDRN | HA Skin Boosters (Profhilo, Skinboosters) |
|---|---|---|
| Primary mechanism | Biological regeneration | Hydration, scaffolding |
| Effect on collagen | Direct stimulation | Indirect (via hydration) |
| Immediate hydration | Modest | Significant |
| Fine lines | Good over series | Good |
| Skin laxity | Moderate | Moderate |
| Under-eye area | Yes (specific formulations) | Risky (HA can cause swelling) |
| Reversible | No (no hyaluronidase) | Yes (hyaluronidase dissolves HA) |
| Evidence base | Growing | Well-established (especially Profhilo) |

Combination approach: Many aesthetic providers use PN and HA boosters together — in the same session or alternating sessions — for complementary effects. The HA provides the immediate hydration response; the PN drives the longer-term regenerative response.

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Who should consider PN/PDRN treatment

Good candidates:
Patients seeking skin quality improvement (texture, radiance, mild laxity) without filler
Patients with thin or delicate skin (periorbital, neck) where other treatments are aggressive
Patients who want a biologically-based regenerative approach
Complement to laser/microneedling protocols
Post-acne skin quality improvement

Not the right choice for:
Patients seeking structural volume (fillers address this)
Patients with severe laxity (device-based or surgical)
Patients wanting immediate visible change (PN results are progressive)

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