Randomized, Controlled, Multicentered, Double-Blind

Investigation of Injectable Poly-L-Lactic Acid for

Improving Skin Quality
Krista Bohnert, BS,* Andrew Dorizas, MD,† Paul Lorenc, MD,‡ and Neil S. Sadick, MD*x

BACKGROUND Poly-L-lactic acid (PLLA) is an injectable filler used for restoring facial fat volume loss.

OBJECTIVE To evaluate the effect of repeated PLLA injections on skin quality.

METHODS Forty healthy women were enrolled in this randomized, controlled, double-blind, multicenter
study. Eligible subjects received 3 treatments every 4 weeks with either PLLA (treatment group) or saline
(control group) injections, into both sides of the face. Follow-up visits were at 6, 9, and 12 after the last
treatment. Assessments included biophysical measuring instruments, live ratings, patient questionnaires, and
rating of standardized pictures by a blinded evaluator.

RESULTS At the 12-month follow-up, there was a statistically significant increase of skin elasticity and
hydration in PLLA-treated subjects and a decrease in transepidermal water loss in both groups. Pigmentation,
erythema, and pore size were significantly decreased, whereas radiance and smoothness were significantly
increased at 12 months per blinded investigator rating in this group. No treatment-related adverse events
occurred.

CONCLUSION Repeated PLLA treatments may improve skin quality in a time-dependent manner.

The authors received funding for this research from Galderma who also provided the PLL. The authors have
indicated no significant interest with commercial supporters.

T he aging process is complex, arising from an

intimate interplay of external (lifestyle and
environment) and internal (genetics) factors. Bone
resorption, fat pad repletion, muscle atrophy, and
changes in skin tone, color, and texture swap the healthy,
youthful look for an aged one. Currently, the use of
injectable soft-tissue fillers and neurotoxins for
correcting the facial changes associated with aging is the
gold standard in aesthetic medicine. Together with
energy-based devices and a daily skincare regime,
patients can achieve natural, long-lasting facial
rejuvenation and reverse the signs of aging, with no
surgery, downtime, or health risks. Although some fillers
such as hyaluronic acid volumize the area of injection
instantly, others such as poly-L-lactic acid (PLLA) are
biostimulatory, activating resident fibroblasts to
produce autologous collagen over time, leading to a
more natural and long-lasting effect. The mechanism
through which PLLA stimulates neocollagenesis, by
triggering a foreign body reaction to the injected
material, succeeded by a cellular inflammatory response
which leads to the formation of vascularized, connective
tissue.1,2 Poly-L-lactic acid is then hydrolyzed into lactate,
converted to pyruvate, and oxidized into carbon
dioxide.3,4 Although the inflammatory response subsides
in 6 months, the extracellular matrix production

*Sadick Dermatology and Research, New York, New York; †Department of Dermatology, School of Medicine, University
of Miami, Miami, Florida ‡Lorenc Aesthetic Plastic Surgery, Aesthetic Science LLC, New York, New York; xDepartment
of Dermatology, Weill-Cornell School of Medicine, New York, New York

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided
in the HTML and PDF versions of this article on the journal’s Web site (www.dermatologicsurgery.org).

© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
· ·
ISSN: 1076-0512 Dermatol Surg 2019;45:718–724 DOI: 10.1097/DSS.0000000000001772

718

© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

continues, leading to a gradual increase in dermal
thickness that lasts at least 2 years.1,5
Poly-L-lactic acid was approved as Sculptra in 2004 by
the Food and Drug Administration (FDA) for the
treatment of HIV-associated lipoatrophy, and as
Sculptra Aesthetic in 2009 for the correction of shal-
low to deep nasolabial folds and other facial wrinkles
in healthy patients.6,7 Common side effects, that usu-
ally resolve within 1 to 7 days, include localized
swelling, tenderness, redness, itching, and bruising.
Nodules and papules that occur several months after
injection have also been reported but can be prevented
with appropriate product dilution, injection depth,
and postinjection massage.8–11
Aside from volumizing the face and improving wrinkles,
anecdotal evidence also suggests that patients’ skin
quality may also improve after PLLA injection, a phe-
nomenon described as the “Sculptra glow.”3,12 To this
end, the objective of this study was to explore the global
effect of repeated injections of PLLA on skin quality.
Based on the investigator’s experience, global skin
quality improvement includes radiance, smoothness,
and pigment uniformity as well as a decrease of erythema
index and pore size. As there is no direct measurement of
skin quality, these measurements serve as a representa-
tive of improved skin quality. Thus, a comprehensive
methodology was applied to assess the study’s objectives
including biophysical measuring instruments, live rat-
ings, patient questionnaires, and rating of standardized
pictures by an evaluator, who was not involved in patient
treatments, and was blinded to the treatment and the
time points at which the pictures were made.
Materials and Methods
Patients
A total of 40 subjects, 20 per research site, were enrolled
in this trial. All subjects provided written informed con-
sent before receiving any study-related procedures. Eli-
gible subjects were healthy women (30–60 years of age,
Fitzpatrick photo skin types I-IV), with shallow to deep
nasolabial fold contour deficiencies or other facial wrin-
kles that agreed not to have any procedures affecting
facial wrinkles (e.g., filler, botulinum toxin, radio-
© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
BOHNERT ET AL
frequency, laser, IPL, and ultrasound) or skin quality
(microdermabrasion, peels, acne treatments, etc.) for the
duration of the study. Negative urine pregnancy test
results were required for women with childbearing
potential before enrollment. Previous therapy with bot-
ulinum toxin, fillers within 12 months of the baseline visit
or treatment with PLLA in the face at any time, precluded
women from participation. Subjects with dermatologic
conditions including acne, rosacea, eczema, psoriasis,
actinic keratosis, severe sun damage, scars, or a history of
keloids were also excluded from the study.
Study Design
This was a randomized, controlled, double-blind,
multicenter study conducted in accordance with the
principles of the Declaration of Helsinki, current GCP
guidelines, and IRB approval. The treatment phase
consisted of 3 visits at 4-week intervals during which
eligible subjects received injections of PLLA (Sculptra
Aesthetic) for the treatment group or saline (bacterio-
static water) for the control group into the
submalar/midcheek area. Twenty-four hours before
injection, 5 mL of sterile water was added to the PLLA
vial, and after this initial reconstitution, another 2 mL
of sterile water was added. Immediately before the
injections, an additional 2 mL of 1% lidocaine was
added for a final dilution of 9 mL of PLLA. Injections
were performed in tunneling technique into the deep
dermis in a grid pattern using a 25-G needle (1.0 or 1.5
inches) at a 30 to 40° entry angle. Subjects received a
total of up to 5 to 6 mL of PLLA per side. To ensure even
product distribution, and prevent nodule formation,
the injected area was massaged after every 2 to 3
injections and longer at the end of treatment. Patients
were instructed to massage the injected areas for
5 minutes, 5 times per day, for 5 days after the pro-
cedure. The follow-up phase consisted of visits at
months 6, 9, and 12 after the last treatment. Stan-
dardized photographs, investigator evaluations, and
patient questionnaires were taken at baseline and 6, 9,
and 12 months after the last treatment. Biophysical
measurements were taken at baseline, 6, 9, and
12 months after the last treatment. The primary end
point was defined as the degree of improvement in skin
quality measured by a blinded, trained evaluator using
standardized pictures, and live evaluations rated by a
blinded investigator and subjects. Secondary end points
45:5:MAY 2019 719
 BIOLOGIC ACTIVITY OF PLLA
were defined as increase in skin hydration, elasticity, a
decrease in transepidermal water loss (TEWL), and
patient satisfaction.
Assessments
Skin Quality Rating
The assessment of skin quality was performed by
patients, and a trained investigator blinded to the visit
number at baseline and months 6, 9, and 12 using a
customized 10-point scale (see Supplementary Digital
Content 1, Table, http://links.lww.com/DSS/A127).
Subject Satisfaction
Each patient’s satisfaction with their facial appearance
was assessed at every visit using the subject satisfaction
assessment scale: 2 very satisfied, 1 satisfied, 0 no
opinion, 21 unsatisfied, and 22 very unsatisfied.
Standardized Photography
Standardized photographs were taken at 0, 45, and
315° angles using the Visia CR system (Canfield
Imaging Systems, Fairfield, New Jersey).
Skin Physiology
All measurements were performed at baseline, and at
the 6-, 9-, and 12-month visits. Stratum corneum
hydration was assessed using a Corneometer CM 825
(Courage & Khazaka, Cologne, Germany) that deter-
mines hydration by measuring the electrical capacity of
the skin. Transepidermal water loss was assessed
using a Tewameter TW300 (Courage & Khazaka), an
open-chamber method that indirectly measures the
density gradient of water evaporation from the skin.
Skin elasticity was measured using a Cutometer MP580
(Courage & Khazaka), a suction chamber device that
measures the vertical deformation of the skin when
pulled/released into the probe by a controlled vacuum.
Safety
Adverse events were monitored and recorded
throughout the study. Patients were asked to report
product-related adverse events.
720 DERMATOLOGIC SURGERY
© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Statistical Analysis
Ordinal variables were analyzed using Wilcoxon test
for paired samples. For ratio-scaled variables, normal
distribution was verified by Kolmogorov–Smirnov test
and then analyzed using Student t-test for paired vari-
ables or Wilcoxon test. All statistical tests were two-
sided and tested in conjunction with a 0.05 nominal
significance level. Analyses were performed using SAS
version 9.4 statistical software (Cary, NC).
Results
Of the 40 patients enrolled in the study, 7 (4 from the
treatment and 3 from the control group) were
excluded from the statistical analysis because they
were lost to follow-up.
Responder Rates
All skin quality assessments (radiance, smoothness,
pigmentation, erythema, and pore size) were statis-
tically significantly improved at the 12-month visit
according to the blinded investigator ratings (Figure
1). At the 9-month visit, there was also statistically
significant improvement in the mean erythema in the
PLLA-treated group compared with the saline group
(Table 1). Analysis of the subject skin quality mean
scores showed a trend for all assessments to be
increased at the 12-month follow-up in the PLLA
group compared with saline (Figure 2). There was
statistically significant improvement only for pore
size at 12 months.
Patient Satisfaction
Patient satisfaction was higher in the PLLA-treated
group (87.5%) compared with the saline group (55%)
at 6 months, a time point where the PLLA clinical
effect peaks,13 and remained increased compared with
control for the duration of the study (at the 9- and 12-
month follow-up visit) (Figures 3 and 4).
Skin Physiology
Transepidermal water loss was significantly lower
than baseline levels at each post-treatment visit (p-
value < .0001) for both groups. There was a greater
reduction in TEWL loss at 12 months from baseline in
 BOHNERT ET AL

Figure 1. Mean skin quality scores based on an investigator blinded to the visit number at baseline (black bar) and 12-
month follow-up visit (gray bar). P = poly-L-lactic acid treatment; S = saline treatment. Asterisk (*) signifies statistical
significance.

the PLLA-treated group compared with placebo (26%
vs 18%) (data not shown), but the results were not
statistically significant. Stratum corneum hydration
increased statistically significantly from baseline at the
12-month follow-up visit in the PLLA-treated group
compared with control (p < .0001). The increase in
hydration noted in the PLLA group was significantly
associated with time (p = .0005) (Figure 5). Elasticity
also was significantly increased at 12 months in the
PLLA-treated group compared with control
(p = .0017), and this increase was also associated with
time (p = .0004) (Figure 6).
Safety
No adverse events related to the treatment were
reported. The safety profile of PLLA was similar to
that reported in the literature,14 with mild self-
resolving side effects occurring in a few patients.15,16
Temporary swelling, rated as mild per subject
assessment, that resolved without sequelae within a

TABLE 1. Mean Skin Quality Scores Based on an Investigator Blinded to the Visit Number (I) and Patient
Assessments (P)

Time (mo) 0 6 9 12
Assessments (PLLA; saline)
Radiance
I 4.0; 4.6 4.7; 4.7 6.0; 4.7 5.5; 4.2* (p = .01)
P 4.5; 4.9 6.3; 5.3 6.6; 5.2 6.9; 5.1
Smoothness
I 5.3; 6.0 6.4; 5.9 7.1; 6.0 6.8; 5.5* (p = .01)
P 6.5; 6.5 7.0; 6.3 7.0; 5.8 7.7; 5.5
Pigmentation
I 5.1; 5.0 5.0; 5.1 5.8; 4.8 4.6; 4.6* (p = .03)
P 5.7; 5.5 6.3; 5.8 5.3; 5.3 6.0; 4.0
Erythema
I 7.2; 6.9 7.8; 6.4* 7.4; 7.6* 7.7; 7.2* (p = .04)
P 6.3; 5.7 8.0; 6.2 7.8; 5.8 7.6; 6.1
Pore size
I 5.2; 5.0 7.2; 6.2 6.2; 6.4 6.6; 5.3* (p = .001)
P 5.7; 5.6 7.7; 6.6 8.0; 6.9 8.0; 6.6* (p-0.01)

*Statistical significance.
PLLA, poly-L-lactic acid.

45:5:MAY 2019 721

© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
 BIOLOGIC ACTIVITY OF PLLA

Figure 2. Mean skin quality scores based on patient assessments at baseline (black bar) and 12-month follow-up visit (gray
bar). P = poly-L-lactic acid treatment; S = saline treatment. Asterisk (*) signifies statistical significance.

week occurred after the first injection of PLLA in 3
subjects.
Discussion
This study demonstrates that repeated PLLA
injections improve skin quality. A comprehensive
set of measurements were used to represent
improved skin quality because there is no direct
measure of it.
Although similar observations have been reported
for neurotoxin injections,17 this is the first study
suggesting that aside from its volumizing/contour
correcting functions, PLLA injections have a reju-
venating effect on skin quality. The positive effect of
PLLA injections on skin physiology parameters such
as skin hydration, elasticity, TEWL, and skin quality
assessments (erythema, pigmentation, pore size,
radiance, and smoothness) are hypothesized to be
mainly due to PLLA-dependent neocollagenesis

Figure 3. Representative clinical photographs of a 56-year-old subject before (A) and after (B) 9 months of PLLA treatment.
Reduction of pore size, increased radiance, and smoother more even tone is noted after PLLA treatment. PLLA, poly-L-lactic acid.

722 DERMATOLOGIC SURGERY

© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
 BOHNERT ET AL

Figure 4. Representative clinical photographs of a 59-year-old subject before (A) and after (B) 9 months of PLLA treatment.
Reduction of pore size, increased radiance, and smoother more even tone is noted after PLLA treatment. PLLA, poly-L-lactic
acid.

because increased collagen has been previously been
reported to improve skin quality.18,19 Another
working theory, that can synergize with the above
collagen effect, is that deep dermal soft-tissue
injections stimulate resident adipose stem cells to
secrete growth factors, trigger tissue regeneration,
and ultimately rejuvenate the area of filler
injection.20,21
Limitations of the study include the small number of
subjects, and the fact that only female subjects were
enrolled. Given the large number of men seeking
aesthetic treatments with injectable fillers, it remains
to be verified whether the study results would apply
to them as well. Moreover, subjects enrolled were
combined skin types I-VI. Because skin properties
(TEWL, lipid content, and elasticity) have been
shown to differ depending on patient background,
follow-up studies that stratify patients according to
ethnicity type would be of merit, to identify potential
differential PLLA-treatment effects according to skin
type.22

Figure 5. Percentage of changes from baseline in hydration of the stratum corneum over time in PLLA and saline group.
*p < .05. PLLA, poly-L-lactic acid.

45:5:MAY 2019 723

© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
 BIOLOGIC ACTIVITY OF PLLA
Figure 6. Percentage of changes from baseline in elasticity over time in PLLA and saline group. *p < .05. PLLA, poly-L-lactic
acid.
In sum, results presented herein demonstrate that
repeat treatments of PLLA not only improve contour
deficiencies but may also benefit skin quality.
Acknowledgments Patients provided written consent
for the use of their images.
References
1. Brady JM, Cutright DE, Miller RA, Barristone GC. Resorption rate,
route, route of elimination, and ultrastructure of the implant site of
polylactic acid in the abdominal wall of the rat. J Biomed Mater Res
1973;7:155–66.
2. Lee JC, Lorenc ZP. Synthetic fillers for facial rejuvenation. Clin Plast
Surg 2016;43:497–503.
3. Lorenc ZP. Techniques for the optimization of facial and nonfacial
volumization with injectable poly-l-lactic acid. Aesthet Plast Surg 2012;
36:1222–9.
4. Onesti MG, Monarca C, Rizzo MI, Mazzocchi M, et al. Minimally
invasive combined treatment for Parry-Romberg syndrome. Aesthet
Plast Surg 2009;33:452–6.
5. Moyle GJ, Lysakova L, Brown S, Sibtain N, et al. A randomized open-
label study of immediate versus delayed polylactic acid injections for the
cosmetic management of facial lipoatrophy in persons with HIV
infection. HIV Med 2004;5:82–7.
6. Keni SP, Sidle DM. Sculptra (injectable poly-L-lactic acid). Facial Plast
Surg Clin North Am 2007;15:91–7; vii.
7. Perry CM. Poly-L-lactic acid. Am J Clin Dermatol 2004;5:361–8;
discussion 367–368.
8. The efficacy of massage in reducing nodule formation after poly-L-
lactic acid administration for facial volume loss: a randomized,
evaluator-blinded clinical trial: ERRATUM. Dermatol Surg 2017;43:
1001.
9. Wu DC, Goldman MP. The efficacy of massage in reducing nodule
formation after poly-L-lactic acid administration for facial volume loss:
a randomized, evaluator-blinded clinical trial. Dermatol Surg 2016;42:
1266–72.
10. Narins RS, Baumann L, Brandt FS, Fagien S, et al. A randomized study
of the efficacy and safety of injectable poly-L-lactic acid versus human-
based collagen implant in the treatment of nasolabial fold wrinkles. J
Am Acad Dermatol 2010;62:448–62.
724 DERMATOLOGIC SURGERY
© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
11. Reszko AE, Sadick NS, Magro CM, Farber J. Late-onset subcutaneous
nodules after poly-L-lactic acid injection. Dermatol Surg 2009;35(Suppl
1):380–4.
12. Onesti MG, Troccola A, Scuderi N. Volumetric correction using poly-
L-lactic acid in facial asymmetry: parry Romberg syndrome and
scleroderma. Dermatol Surg 2009;35:1368–75.
13. Chen HH, Javadi P, Daines SM, Williams EF III. Quantitative assessment
of the longevity of poly-L-lactic acid as a volumizing filler using 3-
dimensional photography. JAMA Facial Plast Surg 2015;17:39–43.
14. Bartus C, William Hanke C, Daro-Kaftan E. A decade of experience
with injectable poly-L-lactic acid: a focus on safety. Dermatol Surg
2013;39:698–705.
15. Palm MD, Woodhall KE, Butterwick KJ, Goldman MP. Cosmetic use
of poly-l-lactic acid: a retrospective study of 130 patients. Dermatol
Surg 2010;36:161–70.
16. Rendon MI. Long-term aesthetic outcomes with injectable poly-l-lactic
acid: observations and practical recommendations based on clinical
experience over 5 years. J Cosmet Dermatol 2012;11:93–100.
17. Streker M, Luebberding S, Krueger N, Harrington L, et al. Patient-
reported outcomes after incobotulinumtoxinA treatment for upper
facial wrinkles. Dermatol Surg 2015;41(Suppl 1):S29–38.
18. Baroni Edo R, Biondo-Simoes Mde L, Auersvald A, Auersvald LA, et al.
Influence of aging on the quality of the skin of white women: the role of
collagen. Acta Cir Bras 2012;27:736–40.
19. Mojallal A, Lequeux C, Shipkov C, Breton P, et al. Improvement of skin
quality after fat grafting: clinical observation and an animal study. Plast
Reconstr Surg 2009;124:765–74.
20. Wollina U. Midfacial rejuvenation by hyaluronic acid fillers and
subcutaneous adipose tissue––a new concept. Med Hypotheses 2015;
84:327–30.
21. Wollina U. Facial rejuvenation starts in the midface: three-dimensional
volumetric facial rejuvenation has beneficial effects on nontreated
neighboring esthetic units. J Cosmet Dermatol 2016;15:82–8.
22. Wesley NO, Maibach HI. Racial (ethnic) differences in skin properties:
the objective data. Am J Clin Dermatol 2003;4:843–60.
Address correspondence and reprint requests to:
Neil S. Sadick, MD, Sadick Dermatology, 911 Park
Avenue, New York, NY 10075, or e-mail:
nssderm@sadickdermatology.com