Efficacy of ionization-adjusted PN filler in minimizing injection pain: a randomized, patient-blinded, split-face study
Open accessAbstract
Polynucleotide (PN) fillers are widely used for skin rejuvenation due to their regenerative properties; however, injection-related pain remains a major drawback. This randomized, patient-blinded, split-face study evaluated a novel “ionization-adjusted” PN filler with modified pH and ionic strength designed to reduce injection pain without compromising efficacy. Fifteen participants received 1 mL of conventional PN filler on one side of the face and 1 mL of the ionized PN filler on the other. Pain was assessed using a 10-point Visual Analog Scale (VAS), while wrinkle improvement was evaluated using the Crow’s Feet Grading Scale (CFGS) and Global Aesthetic Improvement Scale (GAIS). The ionized PN filler demonstrated significantly lower pain scores (VAS 3.39 ± 1.81) compared to the conventional filler (VAS 5.04 ± 2.19, p < 0.005), with fewer cases of erythema (40% vs. 60%) and embossing (13.3% vs. 56.7%). Both formulations showed significant improvements in CFGS and GAIS scores without statistical differences. These findings suggest that ionization-adjusted PN filler provides a more comfortable injection experience while maintaining similar clinical efficacy and safety profiles. Level of Evidence I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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No statistically significant between-group difference in CFGS or GAIS scores was identified at any assessment time point.
“no statistically significant between-group difference in CFGS or GAIS scores was identified at any assessment time point”
From Polynucleotides and Polydeoxyribonucleotides for Skin Rejuvenation, Postoperative Scar Prevention, and Wound Healing: A Systematic Review of Randomized Clinical Trials (2026) · cites this paper as [12]
The Results section ('CFGS and GAIS'; page unavailable) states that CFGS did not differ statistically between the two filler groups. It reports GAIS averages at 2, 4, and 12 weeks but gives no between-group significance results for GAIS, so that part of the claim is not established by our copy. Table 4’s CFGS p-values compare follow-up scores with baseline, not the two groups. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPost-procedural erythema occurred in 40% of ionization-adjusted PN filler procedures compared with 60% of conventional PN filler procedures (p=0.0075).
“Post-procedural erythema was observed in 40% of ionization-adjusted PN filler procedures compared with 60% of conventional PN filler procedures (p=0.0075)”
CFGS improvements were maintained through the 12-week follow-up.
“with improvements maintained through the 12-week follow-up”
The ionization-adjusted PN filler produced lower pain scores in 48 of 60 injection procedures (80%).
“with the ionization-adjusted filler producing lower pain scores in 48 of 60 procedures (80%)”
Both PN formulations demonstrated statistically significant improvements in Crow's Feet Grading Scale (CFGS) scores from baseline at two weeks (p<0.001 for both).
“Both formulations demonstrated statistically significant improvements in Crow's Feet Grading Scale (CFGS) scores from baseline at two weeks (p<0.001 for both)”
In a randomized patient-blinded split-face trial of 15 participants, the ionization-adjusted PN filler produced a significantly lower mean VAS pain score (3.39±1.81) than the conventional PN filler (5.04±2.19; p<0.005) across 60 injection procedures.
“Across 60 injection procedures, the mean VAS pain score was significantly lower for the ionization-adjusted formulation (3.39±1.81) compared with the conventional PN filler (5.04±2.19; p<0.005)”
The ionization-adjusted PN formulation is non-inferior in aesthetic efficacy to the conventional PN filler.
“confirming non-inferior aesthetic efficacy for the ionization-adjusted formulation”
Embossing occurred in 13.3% of ionization-adjusted PN filler procedures versus 56.7% of conventional PN filler procedures (p<0.0001).
“embossing occurred in 13.3% versus 56.7% of procedures, respectively (p<0.0001)”
Low-risk judgments were assigned to Yogya et al. [7], Jeon et al. [12], and Kim et al. [13].
“Low-risk judgments were assigned to Yogya et al. [7], Jeon et al. [12], and Kim et al. [13].”
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Research works printed but not linked: 23
- [1]He X, Gao X, Xie W. Research progress in skin aging and immunity. Int J Mol Sci. 2024;25:4101–14. 38612909 PMC11012511 · DOI
- [2]Choi EH. Aging of the skin barrier. Clin Dermatol. 2019;37:336–45. 31345321 · DOI
- [3]Galeano M, Bitto A, Altavilla D, Minutoli L, Polito F, Calo M. Polydeoxyribonucl-eotide stimulates angiogenesis and wound healing in the genetically diabetic mouse. Wound Repair Regen. 2008;16:208–17. 18318806 · DOI
- [4]Lee DW, Hong HJ, Roh H, Lee WJ. The effect of polydeoxyribonucleotide on ischemic rat skin flap survival. Ann Plast Surg. 2015;75:84–90. 25954843 · DOI
- [5]Noh TK, Chung BY, Kim SY, Lee MH, Kim MJ, Youn CS. Novel anti-melanogene-sis properties of Polydeoxyribonucleotide, a popular wound healing booster. Int J Mol Sci. 2016;17:1448–58. 27598132 PMC5037727 · DOI · Paper page
- [6]Lee YJ, Kim HT, Lee YJ, Paik SH, Moon YS, Lee WJ. Comparison of the effects of polynucleotide and hyaluronic acid fillers on periocular rejuvenation: a randomized, double-blind, split-face trial. J Dermatolog Treat. 2022;33:254–60. 32248707 · DOI
- [7]Kim JH, Kim ES, Kim SW, Hong SP, Kim J. Effects of polynucleotide dermal filler in the correction of crow’s Feet using an Antera three-dimensional camera. Aesthet Plast Surg. 2022;46:1902–9. 35357558 · DOI · Paper page
- [8]Lee D, Kim MJ, Park HJ, Rah GC, Choi H, Anh ST. Current practices and perceived effectiveness of polynucleotides for treatment of facial erythema by cosmetic physicians. Skin Res Technol. 2023;29:e13466. 37753681 PMC10485387 · DOI
- [9]Araco A, Araco F, Raichi M. An exploratory study of PN HPT for treating postsurgical atrophic and depressed scars. J Cosmet Dermatol. 2025;24:e16764. 39812340 PMC11734378 · DOI
- [10]Yi KH, Winayanuwattikun W, Kim SY, Wan J, Vachatimanont V, Putri AI. Skin boosters: definitions and varied classifications. Skin Res Technol. 2024;30:e13627. 38481069 PMC10938033 · DOI · Paper page
- [11]Hong JY, Lee YH, Kim H, Park KY. Therapeutic performance of needle injection versus needle-free jet injector system for polynucleotide filler in skin rejuvenation. J Cosmet Dermatol. 2025;24:e16595. 39370844 PMC11743049 · DOI · Paper page
- [12]Smith L, Cockerham K. Hyaluronic acid dermal fillers: can adjunctive lidocaine improve patient satisfaction without decreasing efficacy or duration? Patient Prefer Adherence. 2011;5:133–9. 21448297 PMC3063660
- [13]Usach I, Martinez R, Festini T, Peris JE. Subcutaneous injection of drugs: literature review of factors influencing pain sensation at the injection site. Adv Ther. 2019;36:2986–96. 31587143 PMC6822791 · DOI
- [14]Best CA, Best AA, Best TJ, Hamilton DA. Buffered lidocaine and bupivacaine mixture – the ideal local anesthetic solution? Plast Surg. 2015;23:87–90. PMC4459414 26090348 · DOI
- [15]Jeong GJ, Ahn GR, Park SJ, Hong JY, Kim BJ. A randomized, patient/evaluator-blinded, split-face study to compare the efficacy and safety of polycaprolactone and polynucleotide fillers in the correction of crow’s feet. J Cosmet Dermatol. 2020;19:1593–9. 31680395 · DOI
- [16]Lowe PL, Lowe NJ. Botulinum toxin type B: pH change reduces injection pain, retains efficacy. Dermatol Surg. 2005;31:874–8. 25350125
- [17]Brazeau GA, Cooper B, Svetic KA, Smith CL, Gupta P. Current perspectives on pain upon injection of drugs. J Pharm Sci. 1998;87:667–77. 9607942 · DOI
- [18]Berteau O, Filipe-santos O, Wang T, Rojas HE, Granger C, Schwarzenbach F. Medical devices: evidence and research. Med Devices Evid Res. 2015;8:473–84. PMC4646585 26635489
- [19]Felton LA. Essentials of pharmaceutics. 1st ed. Boca Raton, FL: CRC Press, USA; 2013.
- [20]Hijazi LO, Alghonaim Y, Alraee SA, Alqubaisy Y. Injection site pain, onset and duration of action of botulinum toxin reconstituted in normal saline with and without sodium bicarbonate: a prospective, single-center, randomized, double-blind interventional study. Plast Surg. 2021;1:1–6. PMC9389062 35990391
- [21]Oh YJ, Lee NY, Suh DH, Koh JS, Lee SJ, Shin MK. A split-face study using botulinum toxin type B to decrease facial erythema index. J Cosmet Laser Ther. 2011;13(5):243–8. 21848448 · DOI
- [22]Kawane K, Motani K, Nagata S. DNA degradation and its defects. Cold Spring Harb Perspect Biol. 2014;6:a016394. 24890510 PMC4031964 · DOI
- [23]Lauková L, Konečná B, Janovičová L, Vlková B, Celec P. Deoxyribonucleases and their applications in biomedicine. Biomol. 2020;10(7):1036. PMC7407206 32664541
Cited by
Sorted by citations
Alhussain, A. M., Turki M. Albusayys, S., Alfhadi, M. A., Bu Mozah, S. A., AlShammari, S. S. S., Alanazi, H. A. M., Adil Alqazanli, S., Nouruldeen Alabdullah, A., M. ALrashidi, N., Almazrou, A. A., et al. (2026) · Cureus · doi:10.7759/cureus.112403 · Cited by 1 · see citing works
- Authors
- Jeon, W., Park, M., Kim, S. W., & Kim, J.
- Affiliations
- Yonsei University (KR)
- Corresponding author
- Kim, Jiye
- Venue
- Aesthetic Plastic Surgery
- Published
- 2025-12-08
- Volume
- 50
- Issue
- 7
- Pages
- 2723-2730
- ISSN
- 0364-216X (ISSN-L)
- 1432-5241
- PMC
- PMC13102929
- OpenAlex
- W4417127360
- Cited by
- 1
- References
- 0
- Citations by year
- 2026: 1
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Aesthetic Plastic Surgery (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- BR PHARM
- Topics
- Health Sciences › Medicine › Dermatology › Facial Rejuvenation and Surgery Techniques
- Health Sciences › Medicine › Emergency Medicine › Intramuscular injections and effects
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Keywords
- injection pain, skin rejuvenation, crow's feet, wrinkle improvement, erythema
- MeSH terms
- Dermal Fillers, Procedural Pain, Adult, Cosmetic Techniques, Esthetics, Female, Humans, Injections, Intradermal, Injections, Subcutaneous, Male, Middle Aged, Pain Measurement, Rejuvenation, Skin Aging, Single-Blind Method, Treatment Outcome
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