Nucleofill vs Rejuran: Polynucleotide Skin-Booster Comparison
Nucleofill and Rejuran are both injectable polynucleotides (PDRN/PN). Rejuran is salmon-derived; Nucleofill is trout-derived. Here is how to decide, with indications and cost.
Quick Verdict
Nucleofill and Rejuran are both injectable polynucleotide skin boosters — purified DNA fragments derived from fish that trigger fibroblast activity, reduce inflammation, and rebuild collagen over 3-4 sessions spaced 2-4 weeks apart. Rejuran (Korean, Pharma Research Bio) uses salmon-derived PDRN (polydeoxyribonucleotide) and was first to market in 2014. Nucleofill (Italian, Promoitalia) uses trout-derived polynucleotides in a higher-viscosity formulation. Rejuran has the larger evidence base and provider familiarity in Asia/Europe/US; Nucleofill has specific variants optimised for under-eye hollowing and facial lifting. Both are safer and more minimalist than hyaluronic acid fillers for skin-quality indications.
Side-by-side
| Nucleofill | Rejuran | |
|---|---|---|
| Origin | Italy (Promoitalia) | South Korea (Pharma Research Bio) |
| Source | Trout-derived polynucleotides | Salmon-derived PDRN |
| Variants | Medium, Soft Plus, Strong Plus, Hair | Healer (classic), HB, S, i |
| Molecule size | 10-50 million Da | 50 kDa PDRN |
| Typical protocol | 3 sessions, 3-4 weeks apart | 3-4 sessions, 2-4 weeks apart |
| Primary indications | Skin quality, lifting, eyes | Skin quality, acne scars, eyes |
| Needle vs cannula | Needle (both available) | Needle (both available) |
| Downtime | 2-5 days bumps | 3-7 days papules |
| US availability | Limited (off-label import) | Limited (off-label import) |
| EU/UK/Asia availability | Wide | Wide |
| Cost per session | $300-600 | $400-800 |
| Typical full course | $1,200-2,400 | $1,600-3,200 |
What Polynucleotides Do
Polynucleotides are DNA-derived fragments that act on the skin via three mechanisms:
- Fibroblast activation — PDRN binds adenosine A2A receptors on fibroblasts, increasing proliferation and extracellular matrix synthesis.
- Anti-inflammatory effect — reduces pro-inflammatory cytokines (IL-1, TNF-α) and reactive oxygen species in treated skin.
- Angiogenesis support — small-vessel density increases, improving dermal nutrient supply.
The net clinical effect: improved skin elasticity, reduced pore size, better hydration, reduced fine lines, and — for some patients — modest volume restoration through dermal thickening. Polynucleotides are NOT volume fillers. If you want a tear-trough filled or cheekbone built, you need hyaluronic acid filler. Polynucleotides improve skin quality underneath and around those structural treatments.
Key Differences
Source
Rejuran is salmon-derived; Nucleofill is trout-derived. The peptide-nucleotide profile differs slightly. No allergy data shows a meaningful difference in reaction rates.
Molecule size and viscosity
Nucleofill uses longer polynucleotide chains (10-50 million Da) in a more viscous gel; Rejuran uses shorter PDRN fragments (50 kDa) in a more liquid preparation. The difference matters clinically:
- Nucleofill's viscosity gives it slightly more lifting/volumising capacity, especially the Strong Plus variant
- Rejuran's lower viscosity spreads more evenly through the dermis for diffuse skin-quality improvement
Variant specialization
- Rejuran Healer — classic, general-purpose skin quality
- Rejuran HB — paired with hyaluronic acid for hydration-focused results
- Rejuran S — higher concentration, for acne scars and fibrotic tissue
- Rejuran i — specifically formulated for delicate under-eye area
- Nucleofill Medium — baseline skin-quality improvement
- Nucleofill Soft Plus — designed for under-eye hollowing
- Nucleofill Strong Plus — lifting/volumising focus, jawline and cheeks
- Nucleofill Hair — scalp/hair regeneration indication
Evidence base
Rejuran has the larger published evidence base (2014 onwards) with Korean and Italian trials specifically on facial rejuvenation and acne scarring. Nucleofill's evidence is smaller but growing.
When to Pick Nucleofill
- Specific indication for Nucleofill Soft Plus (under-eye hollowing) or Strong Plus (lift)
- Patient prefers more-viscous gel with perceivable volume support
- Provider has specific Nucleofill training and case experience
- Acne scarring is not the primary concern
When to Pick Rejuran
- Acne-scar-focused treatment (Rejuran S)
- Under-eye refinement with Rejuran i (thin skin, delicate area)
- Patient wants the option most widely studied and practitioner-familiar in the region
- Combination with HA filler in the same session (Rejuran HB pairs well)
- Larger evidence base matters to you
Safety and Recovery
Both polynucleotide products have excellent safety profiles. Common side effects:
- Visible papules or bumps at injection sites for 3-7 days (this is expected, not an adverse event)
- Mild bruising
- Transient tenderness
- Very rare: infection, vascular occlusion (<1% with experienced injectors)
Contraindications:
- Active infection at treatment site
- Autoimmune disease in active flare
- Pregnancy or breastfeeding
- Fish allergy (rare but real — anaphylaxis risk)
- Recent (within 2 weeks) dental work
Stacking With Other Treatments
Polynucleotides play well with:
- Hyaluronic acid filler — done first, polynucleotides improve the overlying skin quality
- Microneedling — alternate sessions for compounded collagen induction
- Botox — safe to do concurrently; neurotoxin doesn't affect polynucleotide action
- Morpheus8 / RF — space 2-4 weeks apart
Skip polynucleotides during active retinol/tretinoin use in that skin zone — temporarily pause retinoids for 5-7 days before and after.
Frequently Asked Questions
What is the difference between Nucleofill and Rejuran?
Nucleofill is Italian, trout-derived, and uses higher-molecular-weight polynucleotides in a more viscous gel with variants specialised for under-eye hollowing (Soft Plus) and facial lifting (Strong Plus). Rejuran is Korean, salmon-derived, uses shorter-chain PDRN in a more liquid preparation, has the larger evidence base, and offers variants for acne scarring (Rejuran S) and delicate under-eye treatment (Rejuran i). Neither is universally better.
How many sessions of Nucleofill or Rejuran do you need?
Both Nucleofill and Rejuran protocols call for 3-4 sessions spaced 2-4 weeks apart for the initial course, followed by maintenance every 6-12 months. Single-session results are subtle; the compound effect over the full course drives visible improvement. Patients who treat only once and judge at 4 weeks typically under-rate both products.
Are Nucleofill and Rejuran safe?
Both polynucleotide products have excellent safety profiles with low rates of serious adverse events. The main contraindication is fish allergy (rare but real — anaphylaxis risk). Expected short-term effects include 3-7 days of visible bumps at injection sites, mild bruising, and transient tenderness. Choose a provider with specific polynucleotide training.
Do Nucleofill and Rejuran work on under-eye dark circles?
Both have variants (Rejuran i, Nucleofill Soft Plus) specifically formulated for the under-eye area. They improve thin-skin circles and fine crepiness through dermal thickening and fibroblast activation, but they do NOT fill hollow tear troughs — that remains a hyaluronic acid filler indication. For patients with thin-skin shadow circles plus mild hollowing, combining tear-trough HA filler with polynucleotide skin-booster treatment gives the best aesthetic outcome.
Bottom Line
Nucleofill and Rejuran are two branded versions of the same general concept — injectable polynucleotide skin boosters — with different source species, viscosity profiles, and variant specialisations. Rejuran has the larger evidence base and broader provider familiarity. Nucleofill has specific variants (Soft Plus, Strong Plus) optimised for under-eye and facial-lifting indications. Pick based on your primary concern and your provider's experience with the specific product.
