Journal of Plastic, Reconstructive & Aesthetic Surgery 82 (2023) 92–102

A multicenter, randomized, double-blind,

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comparative study of a multiphasic

hyaluronic acid filler and existing
hyaluronic acid fillers for temporary
restoration of the midface volume of Asian
individuals
Changryul Claud Yi a,b, Hyung Min Hahn c, Hyoseob Lim c,
⁎
Young Joon Kim d, Young Woong Choi d, Joo Hyoung Kim a,b,

a
Department of Plastic and Reconstructive Surgery, Pusan National University, School of Medicine, Busan,
Republic of Korea
b
Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
c
Department of Plastic and Reconstructive Surgery, Ajou University School of Medicine, Suwon, Gyeonggi,
Republic of Korea
d
Department of Plastic and Reconstructive Surgery, Sanggye Paik Hospital, School of Medicine, Inje
University, Seoul, Republic of Korea

Received 9 August 2022; Accepted 29 January 2023

KEYWORDS Summary Background: Giselleligne is the world’s first multiphasic gel product that evenly
Dermal filler; surrounds particles. In the current study, Giselleligne was compared with other existing fillers
Giselleligne; to evaluate their clinical use, safety, and ability to improve midface volume deficits of Asian
Hyaluronic acid; individuals.
Midfacial volume; Methods: A comparative experiment was conducted to gain an understanding of the physical
Esthetic properties of Giselleligne, which is a multilayered hyaluronic acid filler, and to compare its
properties with those of existing hyaluronic acid fillers. The primary outcome of this study was
a Midface Volume Deficit Scale (MFVDS) score improvement at 24 weeks after the procedure.
The secondary outcomes were as follows: MFVDS score improvement after the procedure;
MFVDS score changes after the procedure; Global Esthetic Improvement Scale (GAIS) scores as

⁎
Correspondence to: Department of Plastic and Reconstructive Surgery, School of Medicine, Pusan National University, 179, Gudeok-ro,
Seo-gu, Busan 49241, Republic of Korea.
E-mail address: [email protected] (J.H. Kim).

https://doi.org/10.1016/j.bjps.2023.01.049
1748-6815/© 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
 Journal of Plastic, Reconstructive & Aesthetic Surgery 82 (2023) 92–102

evaluated by the operator after the procedure; the operator’s satisfaction with the product;
evaluation of the GAIS scores by the patient after the procedure; and pain level of the patient
on the day of the procedure.
Results: Giselleligne exhibited properties that are expected to result in significantly superior
clinical outcomes compared to existing products. Giselleligne was superior not only to the
existing products but also in terms of global esthetic improvement, effect duration, and op­
erator satisfaction. Furthermore, Giselleligne was found significantly safer than the existing
products.
Conclusion: Giselleligne is a safer, more user-friendly, and more effective alternative to ex­
isting products for improving the midfacial volume.
© 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by
Elsevier Ltd. All rights reserved.

Hyaluronic acid dermal fillers are considered ideal for re­ (VYC-20 L; Allergan, Inc, Irvine, CA, USA), Neuramis® Deep
ducing signs of aging and restoring volume in the face be­ (Medytox Inc., Seoul, Republic of Korea), the Chaeum® No. 2
cause they are easy and safe to use.1,2 They are typically (Hugel Pharmaceuticals, Chuncheon, Republic of Korea), and
categorized into two groups, namely monophasic and bi­ Elravie® Deep (Humedix Inc., Anyang, Republic of Korea) were
phasic,3,4 based on variations in cross-linking of the gel. used as controls. A rheometer was used to determine the
Monophasic filler is a gel-type homogenous mixture of low- rheological properties of the cross-linked hyaluronic acid gel.
and high-molecular-weight hyaluronic acid. Monophasic fil­ Measurement conditions included the use of a parallel plate
lers are easy to inject and spread evenly during injection. with a diameter of 25 mm, a plate gap of 1000 µm, and an
Because they are highly cohesive, they may last longer after analysis temperature of 25 ℃. The Modular Compact
injection; however, they have limited moldability. Biphasic Rheometer, MCR 302 (Anton Paar, Graz, Austria) was used to
fillers are a mixture of cross-linked hyaluronic acid particles perform measurements. Rheological properties were obtained
in a non-cross-linked hyaluronic acid solution. Therefore, by adding a sinusoidal oscillatory shear strain of γ = γ0 sin ωt,
biphasic fillers may have better mechanical properties and which gradually increased to the angular frequency ω = ω (t)
moldability and can be easily customized according to the with time (t), to the sample while maintaining a constant
anatomical location and indication for treatment.5 How­ strain frequency (γ); then, the response was measured.
ever, their injectability is limited by their hydrogel par­ Thereafter, the angular frequency was increased stepwise up
ticles. to ω = 0.025–10 rad/s on a logarithmic scale. Finally, elasticity
In response to the increasing global demand for dermal (storage modulus, G′), viscosity (loss modulus, G”), and com­
fillers, various product improvements have been under­ plex viscosity (G*) were measured.
taken. Recently, a new multiphasic dermal filler was in­
troduced to overcome the shortcomings of existing fillers.
Giselleligne (CGBio Inc., Seoul, Republic of Korea) is the Cohesiveness comparison
world’s first multiphasic product comprising hyaluronic acid
mixed using the revolution-rotation method with R2 tech­ To evaluate cohesiveness, Yvoire® Volume Plus (LG Chem
nology so that the gel evenly surrounds particles.4 This Ltd., Seoul, Republic of Korea) was used as a control and
multiphasic filler has high viscoelasticity; therefore, it is compared with Giselleligne. After adding 700 mL of 1X
expected to be evenly distributed in high volumes after phosphate-buffered saline in a 1000-mL beaker, a 2.5-cm
injection. During this study, the feeling during injection, magnetic bar was added; then, stirring at 160 rpm was
safety, and effectiveness of improving the midface volume performed. Cohesiveness was confirmed after adding 1 mL
deficits provided by Giselleligne were compared with those of filler at a height of 2 cm from the water surface.
of existing fillers used for Asian individuals with midface
volume deficits.
Hydrating power comparison

To evaluate the hydrating power, VYC-20 L, Elravie® Deep,

Materials and methods The Chaeum® No. 2, Neuramis® Deep, Teosyal® Ultra Deep
(Teoxane, Geneve, Switzerland), and Restylane® Perlane
This study was approved by the Institutional Review Board of (Galderma, Fort Worth, TX, USA) were used as controls and
Pusan National University Hospital (project no. 2006–001–091). compared with Giselleligne. The filler (0.2 mL) and phos­
A comparative experiment was conducted to understand the phate-buffered saline (0.8 mL) were mixed in a 1-mL syringe
physical properties of a new multilayered hyaluronic acid filler and centrifuged at 1500 rpm for 5 min. The hydrating power
(Giselleligne Universal; CGBio Inc., Seoul, Republic of Korea) was confirmed by adding 10 μL of the dyeing reagent. The
and to compare its properties with those of existing products. heights of the hydrated and raised gels of all products were
During the experiment, Juvederm® Voluma® with Lidocaine measured at three points (left, center, and right) (Figure 1).

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 C.C. Yi, H.M. Hahn, H. Lim et al.

Figure 1 Comparison of the hydrating power of various dermal fillers.

Comparison of volume durability MFVDS scores of 1 or more at 1, 4, 8, and 12 weeks after

the procedure were analyzed to determine improvements
To evaluate the volume durability, Yvoire® Volume Plus and compared to the baseline scores. The changes in the MFVDS
VYC-20L were used as controls and compared with scores at 1, 4, 8, 12, and 24 weeks after the procedure were
Giselleligne. General anesthesia was administered to 4- analyzed and compared to the baseline scores. All MFVDS
week-old Sprague-Dawley rats (N = 11) using an in­ scores were evaluated by five plastic surgeons excluding the
traperitoneal injection of Zoletil 50 (0.3 mg/100 g). Then, operator. The GAIS scores were evaluated by the operator
0.5 mL of filler was subcutaneously injected into the dorsal at 1, 4, 8, 12, and 24 weeks after the procedure to de­
skin using a 22-gauge needle. Gross observation and tissue termine any improvements. On the day of the procedure,
biopsy measurements of samples were performed at 1 day the satisfaction of the operator with the product was clas­
and 10 weeks after injection. sified as very good, good, fair, or poor. At 1, 4, 8, 12, and 24
weeks after the procedure, the patients provided GAIS
scores, which were analyzed to determine any improve­
ments. The pain level of the patients on the day of the
Efficacy assessment
procedure was evaluated using a Visual Analog Scale (VAS).
Patients enrolled in this clinical trial were randomly as­
signed to treatment groups. The efficacy of all treatment Safety assessment
products for all eligible patients was analyzed.
The primary outcome of this clinical trial was an im­ After randomization and treatment application, the safety
provement in the Midface Volume Deficit Scale (MFVDS) of all products was assessed. Adverse events were analyzed
score of 1 or more at 24 weeks after the procedure com­ during the clinical trial period. The proportion of patients
pared to the baseline score. The secondary outcomes of this who developed an adverse event (i.e., adverse event in­
clinical trial were improvements in the MFVDS scores, cidence rate) was calculated; in the case of multiple oc­
changes in the MFVDS scores, Global Esthetic Improvement currences of the same adverse event for the same patient,
Scale (GAIS) scores as evaluated by the operator, the op­ the number of occurrences was calculated by individually
erator’s satisfaction with the product, GAIS scores as eval­ counting each case. The incidence rates of application site
uated by the patient, and the pain level of the patient on reactions on the day of the procedure were analyzed
the day of the procedure. as well.

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 Journal of Plastic, Reconstructive & Aesthetic Surgery 82 (2023) 92–102

Figure 2 Rheological properties.

Statistical analysis Results

All statistical analyses were performed using statistical G′ values of 719.7 Pa, 397.2 Pa, 222.8 Pa, 185.8 Pa, and
software (SAS System 9.4; SAS Institute, Cary, NC, USA). A 164.9 Pa were observed for Giselleligne, VYC-20 L,
two-sided test was performed to determine statistical sig­ Neuramis® Deep, The Chaeum® No. 2, and Elravie® Deep,
nificance. Significance was considered at a level of 5%. respectively. G” values of 173.9 Pa, 43.7 Pa, 40.9 Pa,
Group classifications were based on the safety evaluation 33.4 Pa, and 29.4 Pa were observed for Giselleligne, VYC-
and efficacy assessment results. 20 L, Neuramis® Deep, The Chaeum® No. 2, and Elravie®

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 C.C. Yi, H.M. Hahn, H. Lim et al.

The heights of the hydrated and raised gels of

Giselleligne, VYC-20L, Neuramis® Deep, The Chaeum® No.
2, Elravie® Deep, Teosyal® Ultra Deep, and Restylane®
Perlane were 1.12 cm, 1.93 cm, 2.85 cm, 2.88 cm, 4.16 cm,
3.49 cm, and 2.45 cm, respectively. Regarding the results of
the hydrating power comparison, the expansion degree of
Giselleligne was found significantly lower than that of the
other products (p < 0.001) (Figure 1).
A tissue biopsy performed 1 day after injection indicated
the following heights: 8.35 mm for Giselleligne; 7.168 mm for
Yvoire® Volume Plus; and 7.198 mm for VYC-20 L. The height
of Giselleligne was significantly higher than that of the other
products (p < 0.05). At 10 weeks after injection, the heights
of Giselleligne, Yvoire® Volume Plus, and VYC-20 L were
Figure 3 Comparison of cohesiveness. 7.268 mm, 6.362 mm, and 5.638 mm, respectively. Again, the
height of Giselleligne was found significantly higher than that
of the other products (p < 0.05) (Figure 4).

Deep, respectively. Finally, G* values of 117,843.3 cP,

63,596.0 cP, 36,045.0 cP, 30,038.3 cP, and 26,651.7 cP were Efficacy assessment
observed for Giselleligne, VYC-20 L, Neuramis® Deep, The
Chaeum® No. 2, and Elravie® Deep, respectively (Figure 2). During this trial, 107 patients were screened but 102 pa­
It was visually concluded that Giselleligne aggregated tients were enrolled. Of these 102 patients, 100 patients
better than Yvoire® Volume Plus (Figure 3). (98.04%) completed the trial (Table 1). Of them, eight did

Figure 4 Results of the gross observation and tissue biopsy performed to compare the volume durability.

Table 1 Participant information.

Giselleligne VYC-20 L Total

n (%)
Screened 107
Screen failure 5
Clinical trial assignment (random) 54 48 102
Applicable to medical treatment 54 (100.00) 48 (100.00) 102 (100.00)
Normal termination 52 (96.30) 48 (100.00) 100 (98.04)
Dropout/early termination 2 (3.70) 0 2 (1.96)
Patient never visited after application of the medical treatment 1 (1.85) 0 1 (0.98)
Request from patient or legal representative to discontinue participation 1 (1.85) 0 1 (0.98)

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 Journal of Plastic, Reconstructive & Aesthetic Surgery 82 (2023) 92–102

Table 2 Demographic information and baseline characteristics of the patients.

Giselleligne (n = 54) VYC-20 L (n = 48) P-value

n (%), mean ± SD, median

Age (years) 54, 46.31 ± 8.72, 46.50 48, 44.08 ± 8.52, 44.00 0.195 (t)
Sex 0.340 (f)
Male 1 (1.85) 3 (6.25)
Female 53 (98.15) 45 (93.75)
Height (cm) 54, 160.64 ± 5.61, 160.00 48, 161.29 ± 6.40, 160.00 0.888 (w)
Weight (kg) 54, 56.40 ± 7.40, 55.00 48, 56.54 ± 7.67, 55.70 0.965 (w)
Body mass index (kg/m2) 54, 21.82 ± 2.32, 21.31 48, 21.69 ± 2.16, 21.56 0.763 (t)
Smoking 1.000 (f)
Smoker 1 (1.85) 0
Nonsmoker 53 (98.15) 48 (100.00)
Former smoker 0 0
Alcohol 0.776 (c)
Drinker 25 (47.17) 24 (50.00)
Nondrinker 28 (52.83) 24 (50.00)
Medical history/surgical history 24 (53.33) 21(46.67) 0.944 (c)
Previous/concomitant medications 42(53.16) 37(46.84) 0.933 (c)
Usage
Left (mL) 54, 2.63 ± 1.32, 2.50 48, 2.65 ± 1.29, 2.50 0.824 (w)
Right (mL) 54, 2.64 ± 1.28, 2.50 48, 2.64 ± 1.28, 2.50 0.968 (w)
Two sample t-test (t) or Wilcoxon’s rank sum test (w) results were used to compare the means of continuous variables between groups. Chi-
square test (c) or Fisher’s exact test (f) results were used to compare rates of categorical variables between groups. SD, standard deviation.

Table 3 Results of the assessment of changes in the MFVDS scores at 1, 4, 8, 12, and 24 weeks after the procedure compared to
the baseline value and the rates of improvement in MFVDS scores by 1 or more.
Giselleligne (n = 48) VYC-20 L (n = 44) P-value

n (%), mean ± SD, median

Baseline 48, 2.33 ± 0.56, 2.00 44, 2.14 ± 0.35, 2.00
Week 1 48, 0.94 ± 0.48, 1.00 44, 0.84 ± 0.43, 1.00
Week 1 – baseline 48, −1.40 ± 0.61, −1.00 44, −1.30 ± 0.51, −1.00 0.372 (w)
Improved 47 (97.92) 44 (100.00) 1.000 (f)
Unimproved 1 (2.08) 0
Week 4 48, 1.02 ± 0.39, 1.00 44, 1.02 ± 0.40, 1.00
Week 4 – baseline 48, −1.31 ± 0.62, −1.00 44, −1.11 ± 0.49, −1.00 0.123 (w)
Improved 46 (95.83) 41 (93.18) 0.667 (f)
Unimproved 2 (4.17) 3 (6.82)
Week 8 48, 1.00 ± 0.29, 1.00 44, 1.00 ± 0.37, 1.00
Week 8 – baseline 48, −1.33 ± 0.60, −1.00 44, −1.14 ± 0.46, −1.00 0.111 (w)
Improved 47 (97.92) 42 (95.45) 0.605 (f)
Unimproved 1 (2.08) 2 (4.55)
Week 12 48, 1.02 ± 0.39, 1.00 44, 0.98 ± 0.40, 1.00
Week 12 – baseline 48, −1.31 ± 0.72, −1.00 44, −1.16 ± 0.48, −1.00 0.298 (w)
Improved 44 (91.67) 42 (95.45) 0.679 (f)
Unimproved 4 (8.33) 2 (4.55)
Improvement rate difference [95% CI] -3.79 [−13.74, 6.16]
Lower limit > −15%? Yes
Week 24 48, 1.08 ± 0.35, 1.00 44, 1.00 ± 0.30, 1.00
Week 24 – baseline 48, −1.25 ± 0.56, −1.00 44, −1.14 ± 0.35, −1.00 0.254 (w)
Improved 46 (95.83) 44 (100.00) 0.496 (f)
Unimproved 2 (4.17) 0
Improvement rate difference [95% CI] -4.17 [−9.82, 1.49]
Lower limit > −15%? Yes
CI, confidence interval; MFVDS, Midface Volume Deficit Scale; SD, standard deviation.
Wilcoxon’s rank sum test (w) results were used to compare the means of continuous variables between groups. Fisher’s exact test (f)
results were used to compare rates of categorial variables between groups.

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 C.C. Yi, H.M. Hahn, H. Lim et al.

Table 4 Results of the assessment of improvement rates of the global esthetic improvement scale scores at 1, 4, 8, 12, and 24
weeks after the procedure as evaluated by the operator.
Giselleligne (n = 48) VYC-20L (n = 44) P-value

n (%), mean ± SD, median

Week 1 48, 4.46 ± 0.58, 4.50 44, 4.11 ± 0.58, 4.00 0.006
Improved 48 (100.00) 44 (100.00)
Unimproved 0 0
Week 4 48, 4.52 ± 0.68, 5.00 44, 4.02 ± 0.70, 4.00 0.001
Improved 48 (100.00) 44 (100.00)
Unimproved 0 0
Week 8 48, 4.44 ± 0.68, 5.00 44, 3.77 ± 0.68, 4.00 < 0.001
Improved 48 (100.00) 44 (100.00)
Unimproved 0 0
Week 12 48, 4.56 ± 0.54, 5.00 44, 3.77 ± 0.77, 4.00 < 0.001
Improved 48 (100.00) 44 (100.00)
Unimproved 0 0
Week 24 48, 4.44 ± 0.68, 5.00 44, 3.84 ± 0.75, 4.00 < 0.001
Improved 48 (100.00) 44 (100.00)
Unimproved 0 0
SD, standard deviation.
Wilcoxon’s rank sum test (w) results were used to compare means between groups.

not comply with the study protocol; therefore, a total of 92 Therefore, the difference between the Giselleligne group
patients (48 in the Giselleligne group and 44 in the VYC-20L and the VYC-20 L group in terms of improvement was
group) were included as the final subjects. −4.17% and the lower limit of the 95% confidence interval
The mean age of the patients in the Giselleligne group was −9.82%, which was larger than the noninferiority
was 46.31 years. The mean age of the patients in the VYC- margin of −15%, indicating statistical noninferiority
20 L group was 44.08 years. Therefore, there was no sta­ (Table 3).
tistically significant difference in age between these groups At 1, 4, 8, and 12 weeks after the procedure, the rates of
(p = 0.195). There were 53 women and one man in the improvement in the MFVDS scores of 1 or more were 97.92%,
Giselleligne group. There were 45 women and three men in 95.83%, 97.92%, and 91.67% in the Giselleligne group, re­
the VYC-20 L group. No statistically significant difference spectively, and 100.0%, 93.18%, 95.45%, and 95.45% in the
was observed in sex between these groups (p = 0.340). VYC-20 L group, respectively. The differences in the rates
There were no significant differences in the height, weight, between the two groups at all time points were not statis­
or body mass index (BMI) of patients in these groups (height: tically significant (1 week: p = 1.000; 4 weeks: p = 0.667; 8
p = 0.888; weight: p = 0.965; BMI: p = 0.763). Any differ­ weeks: p = 0.605; 12 weeks: p = 0.679) (Table 3).
ences in other characteristics of these groups were not At 1, 4, 8, 12, and 24 weeks after the procedure, the
statistically significant (Table 2). mean changes in MFVDS scores compared to the baseline
The rate of improvement in MFVDS scores of 1 or more at score were −1.40, −1.31, −1.33, −1.31, and −1.25, re­
24 weeks after the procedure compared to the baseline spectively, in the Giselleligne group, and −1.30, −1.11,
score was 95.83% (46/48) in the Giselleligne group; how­ −1.14, −1.16, and −1.14, respectively, in the VYC-20 L
ever, it was 100.00% (44/44) in the VYC-20 L group. group. The mean differences between groups were not
statistically significant at 1, 4, 8, 12, and 24 weeks after the
Table 5 Results of the assessment of the operator’s sa­ procedure (1 week: p = 0.372; 4 weeks: p = 0.124; 8 weeks:
tisfaction with treatment. p = 0.111; 12 weeks: p = 0.298; 24 weeks: p = 0.254)
(Table 3).
Giselleligne VYC-20L P-value The mean GAIS scores at 1, 4, 8, 12, and 24 weeks after
(n = 48) (n = 44) the procedure were 4.46, 4.52, 4.44, 4.56, and 4.44, re­
spectively, in the Giselleligne group, and 4.11, 4.02, 3.77,
n (%)
3.77, and 3.84, respectively, in the VYC-20 L group. The
Satisfaction < 0.0001 mean difference between groups was statistically sig­
Very good 45 (93.75) 12 (27.27) nificant for all cases at 1, 4, 8, 12, and 24 weeks after the
Good 3 (6.25) 30 (68.18) procedure (1 week: p = 0.006; 4 weeks: p = 0.001; 8 weeks:
Fair 0 2 (4.55) p < 0.001; 12 weeks: p < 0.001; 24 weeks: p < 0.001).
Poor 0 0 GAIS score improvement rates at 1, 4, 8, 12, and 24 weeks
Fisher’s exact test (f) results were used to compare rates between after the procedure in both the Giselleligne and VYC-20 L
groups. groups were classified as improved (Table 4).

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 Journal of Plastic, Reconstructive & Aesthetic Surgery 82 (2023) 92–102

Table 6 Results of the assessment of the improvements in GAIS scores at 1, 4, 8, 12, and 24 weeks after the procedure as
evaluated by the patient.
Giselleligne (n = 48) VYC-20 L (n = 44) P-value

n (%), mean ± SD, median

Week 1 48, 4.17 ± 0.81, 4.00 44, 3.84 ± 0.83, 4.00 0.042 (w)
Improved 1 (2.08) 3 (6.82) 0.346 (f)
Unimproved 47 (97.92) 41 (93.18)
Week 4 48, 4.06 ± 0.70, 4.00 44, 3.75 ± 0.81, 4.00 0.052 (w)
Improved 0 1 (2.27) 0.478 (f)
Unimproved 48 (100.00) 43 (97.73)
Week 8 48, 3.98 ± 0.84, 4.00 44, 3.68 ± 0.77, 4.00 0.061 (w)
Improved 2 (4.17) 1 (2.27) 1.000 (f)
Unimproved 46 (95.83) 43 (97.73)
Week 12 48, 4.00 ± 0.83, 4.00 44, 3.64 ± 0.84, 4.00 0.034 (w)
Improved 2 (4.17) 3 (6.82) 0.667 (f)
Unimproved 46 (95.83) 41 (93.18)
Week 24 48, 4.02 ± 0.91, 4.00 43, 3.63 ± 0.79, 4.00 0.029 (w)
Improved 2 (4.17) 2 (4.65) 1.000 (f)
Unimproved 46 (95.83) 41 (95.35)
Wilcoxon’s rank sum test (w) results were used to compare the means of continuous variables between groups. Fisher’s exact test (f) results
were used to compare rates of categorial variables between groups. GAIS, Global Esthetic Improvement Scale; SD, standard deviation.

Table 7 Results of the assessment of the pain level on the day Operator satisfaction in the Giselleligne group was clas­
of the procedure. sified as very good (92.59%) or good (7.41%); however, op­
erator satisfaction in the VYC-20 L group was classified as
Giselleligne VYC-20 L P-value
very good (27.08%), good (68.75%), or fair (4.17%). These
(n = 48) (n = 44)
differences between groups were statistically significant
n, mean ± SD, median (p < 0.001) (Table 5).
At 1, 4, 8, 12, and 24 weeks after the procedure, the
Visual analog 48, 44, 0.1618 mean GAIS scores evaluated by the patients were 4.17,
scale score 2.10 ± 1.55, 2.68 ± 1.81, 4.06, 3.98, 4.00, and 4.02, respectively, in the Giselleligne
2.00 2.00 group, and 3.84, 3.75, 3.68, 3.64, and 3.63, respectively, in
Wilcoxon’s rank sum test (w) results were used to compare means the VYC-20 L group. The mean difference between groups
between groups. was statistically significant at 1, 12, and 24 weeks after the

Table 8 Results of the treatment safety assessment.

Giselleligne (n = 53) VYC-20 L (n = 49) P-value

n (%) [95% CI] Case n (%) [95% CI] Case

Emergent adverse treatment effects 4 (7.55) Mild 7 14 (28.57) Mild 21 0.005 (c)
[0.44, 14.66] Moderate 0 [15.92, 41.22] Moderate 1
Severe 0 Severe 0
Total 7 Total 22
Adverse treatment effects 1 (1.89) Mild 1 4 (8.26) [2.27, 19.60] Mild 5 0.192 (f)
[0.05, 10.07] Moderate 0 Moderate 0
Severe 0 Severe 0
Total 1 Total 5
Serious emergent adverse treatment 0 Mild 0 0 Mild 0 -
effects Moderate 0 Moderate 0
Severe 0 Severe 0
Total 0 Total 0
Serious adverse treatment effects 0 Mild 0 0 Mild 0 -
Moderate 0 Moderate 0
Severe 0 Severe 0
Total 0 Total 0
Chi-square test (c) results or Fisher’s exact test (f) results were used for group comparisons of emergent adverse treatment effect/
adverse treatment effect incidence rates. CI, confidence interval.

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 C.C. Yi, H.M. Hahn, H. Lim et al.

Table 9 Results of the assessment of adverse events by SOC/PT.

SOC/PT Giselleligne (n = 53) VYC-20 L (n = 49)

n (%) [Case]
General disorders and administration site conditions 1 (1.89) [1] 4 (8.16) [5]
Pain 0 2 (4.08) [2]
Granuloma 1 (1.89) [1] 0
Injection site discomfort 0 1 (2.04) [1]
Pyrexia 0 1 (2.04) [1]
Sensation of foreign body 0 1 (2.04) [1]
Gastrointestinal disorders 1 (1.89) [1] 3 (6.12) [4]
Chronic gastritis 0 2 (4.08) [2]
Gastroesophageal reflux disease 1 (1.89) [1] 1 (2.04) [1]
Constipation 0 1 (2.04) [1]
Infections and infestations 3 (5.66) [3] 1 (2.04) [1]
Helicobacter gastritis 1 (1.89) [1] 0
Pharyngitis 1 (1.89) [1] 0
Urinary tract infection 0 1 (2.04) [1]
Vestibular neuronitis 1 (1.89) [1] 0
Nervous system disorders 1 (1.89) [1] 2 (4.08) [3]
Intracranial aneurysm 0 1 (2.04) [2]
Occipital neuralgia 1 (1.89) [1] 0
Piriformis syndrome 0 1 (2.04) [1]
Musculoskeletal and connective tissue disorders 0 3 (6.12) [3]
Arthralgia 0 1 (2.04) [1]
Deformity, thorax 0 1 (2.04) [1]
Osteoarthritis 0 1 (2.04) [1]
Endocrine disorders 0 1 (2.04) [1]
Hypogonadism 0 1 (2.04) [1]
Immune system disorders 0 1 (2.04) [1]
Food allergy 0 1 (2.04) [1]
Neoplasms, benign, malignant, and unspecified (including cysts 1 (1.89) [1] 0
and polyps)
Uterine leiomyoma 1 (1.89) [1] 0
Reproductive system and breast disorders 0 1 (2.04) [1]
Vaginal hemorrhage 0 1 (2.04) [1]
Skin and subcutaneous tissue disorders 0 1 (2.04) [1]
Alopecia 0 1 (2.04) [1]
Surgical and medical procedures 0 1 (2.04) [1]
Breast reconstruction 0 1 (2.04) [1]
Swelling of the face 0 1 (2.04) [1]
Swelling of the face 0 1 (2.04) [1]
PT, Preferred term; SOC, System organ class.

procedure (1 week: p = 0.042; 12 weeks: p = 0.034; 24 Regarding the pain level of patients on the day of the
weeks: p = 0.029); however, at 4 weeks and 8 weeks after procedure, the mean VAS score was 2.10 in the Giselleligne
the procedure, it was not statistically significant (4 weeks: group and 2.68 in the VYC-20L group. This difference between
p = 0.052; 8 weeks: p = 0.061). groups was not statistically significant (p = 0.162) (Table 7).
The GAIS scores as evaluated by the patients at 1, 4, 8,
12, and 24 weeks after the procedure showed considerable
improvement by 97.92%, 100.00%, 95.83%, 95.83%, and Safety assessment
95.83%, respectively, in the Giselleligne group. However, in
the VYC-20L group, these rates were 93.18%, 97.73%, The incidences of emergent adverse treatment effects,
97.73%, 93.18%, and 95.35% at 1, 4, 8, 12, and 24 weeks adverse treatment effects, serious adverse events, serious
after the procedure, respectively. The difference in the adverse reactions to treatment, and unexpected adverse
rates between groups at all time points was not statistically reactions to treatment after the application of filler are
significant (1 week: p = 0.346; 4 weeks: p = 0.478; 8 weeks; summarized in Table 8.
p = 1.000; 12 weeks: p = 0.667; 24 weeks: p = 1.000) In the Giselleligne group, 4 out of 53 patients (7.55%; 7
(Table 6). cases) had an adverse event. In the VYC-20L group, 14 out of

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 Journal of Plastic, Reconstructive & Aesthetic Surgery 82 (2023) 92–102

Table 10 Results of the assessment of adverse reactions Table 11 Results of the assessment of the incidence of
to treatment by SOC/PT. application site reactions on the day of the procedure.
SOC/PT Giselleligne VYC-20 L Symptoms Giselleligne VYC-20 L P-value
(n = 53) (n = 49) (n = 53) (n = 49)

n (%) [Case] n (%)

General disorders and 1 (1.89) [1] 3 (6.12) [4] Local adverse 0 3 (6.12) 0.1073 (f)
administration site events
conditions Tenderness 0 0
Pain 0 2 (4.08) [2] Edema 0 0
Granuloma 1 (1.89) [1] 0 Sclerosis 0 0
Injection site discomfort 0 1 (2.04) [1] Nodule 0 0
Sensation of foreign body 0 1 (2.04) [1] Bruise 0 2 (4.08) 0.2283 (f)
Swelling of the face 0 1 (2.04) [1] Pain 0 0
Swelling of the face 0 1 (2.04) [1] Erythema 0 0
PT, Preferred term; SOC, System organ class. Discoloration 0 0
Pruritus 0 1 (2.04) 0.4804 (f)
49 patients (28.57%; 22 cases) had an adverse event. A Chi-square test (c) results or Fisher’s exact test (f) results were
statistically significant difference in the incidence rates used for group comparisons of local adverse event rates.
between groups was observed (p = 0.005).
In the Giselleligne group, 1 out of 31 patients (1.89%; 1
case) had an adverse reaction to treatment. In the VYC-20L Giselleligne was expected to have relatively superior safety
group, 4 out of 49 patients (8.26%; 5 cases) had an adverse because its degree of expansion was significantly lower than
reaction to treatment. No statistically significant difference that of other products.
was observed in the incidence rates between groups Giselleligne exhibited physical properties that were ex­
(p = 0.192). No patient developed any serious adverse pected to result in superior clinical outcomes compared
events, serious adverse reactions to treatment, or un­ with the existing products evaluated. The comparison of the
expected adverse reactions to treatment (Tables 9 and 10). physical properties of the fillers applied to actual patients
No local adverse events occurred in the Giselleligne group; demonstrated similar results.
however, 3 out of 49 patients (6.12%; 3 cases) in the VYC-20L The objective of the current study was to show that
group experienced local adverse events (2 cases of bruises Giselleligne was not inferior to VYC-20 L. The improve­
and 1 case of pruritus). There was no statistically significant ments of the MFVDS scores of 1 or more at 24 weeks after
difference in the incidence rates between groups the procedure compared to the baseline scores were ana­
(p = 0.107) (Table 11). lyzed, and the difference in the improvement rates be­
tween the Giselleligne group and the VYC-20 L group was
− 5.77%. The lower limit of the 95% confidence interval
was −12.11%, which was larger than the non-inferiority
Discussion margin of −15%, indicating that Gisellegligne was not in­
ferior to VYC-20 L.
During this study, Giselleligne and other existing fillers used The GAIS score improvement evaluated by the operator
for patients with midface volume deficits were compared. was classified as improved in the Giselleligne group and the
Giselleligne had a significantly higher storage modulus than VYC-20 L group; however, the mean GAIS score of the
the control products. The higher the storage modulus of the Giselleligne group was significantly higher. The satisfaction
dermal filler, the better its ability to accumulate volume, level of the operator on the day of the procedure was higher
and the longer that volume is maintained. for Giselleligne than for VYC-20 L, and this difference was
The loss modulus (G”) represents the resistance to dy­ statistically significant.
namic forces as a measure of energy lost as heat. The higher Our results demonstrated that Giselleligne is superior to
the resistance to dynamic forces, the better the stickiness. not only VYC-20 L but also in terms of global esthetic im­
The G” value of Giselleligne filler was also significantly provement, duration of the effects, and operator sa­
higher than that of the control products. tisfaction.
Complex viscosity (G*) is the sum of the elastic modulus Giselleligne was found to be significantly safer than VYC-
and the viscous modulus. Giselleligne had a significantly 20 L. Incidence rates of emergent adverse treatment effects
higher G* value than the control products, suggesting its (which showed a significant difference), adverse treatment
high viscoelasticity and superior durability. The cohesive­ effects, and local adverse events on the day of the proce­
ness comparison performed to evaluate volume retention dure were lower for Giselleligne. Therefore, Giselleligne is
after the procedure also showed that Giselleligne had sig­ superior to VYC-20 L in terms of efficacy and safety.
nificantly better cohesiveness than the other products. This study had some limitations. There was a lack of
If the hyaluronic acid filler is not sufficiently hydrated, consistency in injection techniques and evaluation criteria
then it will absorb the moisture of the surrounding tissue by because multiple surgeons participated in this study.
osmotic pressure and expand, thereby causing swelling and Therefore, this study tried to address this problem by in­
edema; therefore, the hydrating power is important. cluding five experts (excluding the operator).

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 C.C. Yi, H.M. Hahn, H. Lim et al.

The follow-up period of 24 weeks was another limitation. This clinical study was registered retrospectively as
A longer follow-up period could provide more reliable re­ KCT0008324 in the Clinical Research Information System.
sults regarding the effectiveness of the products in terms of
volume restoration and durability. Therefore, a longer-term
follow-up study is suggested in studies in the future. Financial disclosure statement

The authors have no commercial associations or financial

Conclusion disclosures to declare.

To the best of our knowledge, this is the first study to

compare Giselleligne with existing products in terms of Declaration of Competing Interest
physical and clinical properties. Giselleligne exhibited sig­
nificantly higher viscoelasticity related to volume con­
None.
tinuity compared with the other products, and the restored
volume resulting from the use of Giselleligne lasted sig­
nificantly longer. Additionally, according to the patients,
the feeling of the injection associated with Giselleligne was References
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