Split‑face PN study: depth matters less than comfort
Split‑face prospective study finds polynucleotide delivered subdermally is non‑inferior to intradermal for wrinkle improvement and better tolerated
- By
- Ian Gauntt, RN, BSN
- Filed under
- Treatments
- Published
- September 17, 2026
- Sources cited
- 7
- Evidence
- Tier 2 · Professional & trade
Key Takeaways
- Subdermal polynucleotide delivery matched intradermal in reducing fine wrinkles.
- Subdermal injections resulted in lower pain scores across sessions.
- Intradermal delivery caused visible embossing; subdermal did not.
- Objective skin-quality indices improved similarly with both approaches.
- Split-face design controlled for individual variability.
What did the split-face prospective study on polynucleotide delivery depth investigate?
This 2026 prospective split-face study compared intradermal versus subdermal injection of a polynucleotide-based injectable over three sessions spaced three weeks apart. Researchers assessed wrinkle improvement via Antera 3D fineline index at Week 12 with a non-inferiority margin of −15% for percent improvement (pmc.ncbi.nlm.nih.gov).
Did subdermal delivery prove non-inferior for wrinkle improvement?
Subdermal delivery met the non-inferiority criterion at Weeks 9 and 12. At Week 12, the fineline index was lower (better) on the subdermal side than on the intradermal side (p = 0.005) (pmc.ncbi.nlm.nih.gov). Other Antera 3D indices—wrinkle, roughness, pores, tone, elasticity—improved comparably, though these findings were exploratory and not multiplicity-adjusted (pmc.ncbi.nlm.nih.gov).
How did tolerability compare between injection depths?
Participants reported lower post-procedure pain on the subdermal cheek across all sessions when measured on the visual analog scale (pmc.ncbi.nlm.nih.gov). Injection-site embossing occurred only with intradermal injections; subdermal injections produced none (pmc.ncbi.nlm.nih.gov).
What does split-face design add to the findings?
Each participant received both treatments—left cheek intradermal, right cheek subdermal—eliminating inter-individual variability. That design strengthens the conclusion that differences in pain and embossing stem from delivery depth rather than patient factors (pmc.ncbi.nlm.nih.gov).
What are the practical implications of these results?
Clinicians can consider subdermal polynucleotide delivery when short-term skin-quality improvement and patient comfort matter. It delivers wrinkle reduction comparable to intradermal methods but with less discomfort and no visible embossing (pmc.ncbi.nlm.nih.gov).
FAQ
What is polynucleotide delivery depth in this study?
It refers to the comparison between intradermal injection (within the dermis) and subdermal injection (beneath the dermis) of a polynucleotide-based injectable in a split-face design.
Did subdermal polynucleotide delivery depth perform as well as intradermal for wrinkle improvement?
Yes. Subdermal delivery met non-inferiority for wrinkle reduction by Week 12 and showed a lower fineline index on that side compared to intradermal delivery.
Which injection method was more comfortable—subdermal or intradermal polynucleotide delivery?
Subdermal delivery caused less pain than intradermal delivery across all treatment sessions.
Did injection-site embossing differ with polynucleotide delivery depth?
Yes. Only the intradermal side had visible embossing. The subdermal side showed none.
What does split-face polynucleotide delivery depth study design control for?
By treating each cheek differently in the same person, the split-face design controls for individual skin and healing differences, isolating the impact of delivery depth.
This article is for general information and is not medical advice. Aesthetic treatment results vary by individual—consult a licensed, qualified provider before pursuing any cosmetic procedure.
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