Received: 30 May 2022 | Revised: 21 November 2022 | Accepted: 13 December 2022

DOI: 10.1111/jocd.15595

LETTERS TO THE EDITOR

Early-­stage volume effect difference between injectable poly-­

l-­lactic acid and injectable poly-­d,l-­lactic acid

To the editor, volume PDLLA microspheres. Based on previous studies,4,6 we can

Biostimulators, or collagen-­stimulating fillers, have been increasing find out that the porous PDLLA microspheres can not only stimulate
in popularity for facial rejuvenation in recent years. Among these bi- neo-­tissues formation but also provide scaffolds for them. The neo-­
ostimulators, injectable poly-­l-­lactic acid (PLLA; Sculptra; Galderma) tissues first grow on the surface of these microspheres, then they
was first available in Europe in 1999.1,2 Another biostimulator, in- grow more to fill the interspace of microspheres. At the same time,
jectable poly-­d,l-­lactic acid (PDLLA; AestheFill; REGEN), was first these porous microspheres degrade gradually while neo-­tissues
approved for use in South Korea in 2014. 2–­4 They are both supplied grow inside microspheres. The original volume of these microsphere
as lyophilized powders in vials, which need to be reconstituted with scaffolds is replaced by neo-­tissues and remains the same in the fol-
sterile water before injection.1–­3 Although they are identical, there lowing months. For better understanding of the PDLLA collagen for-
are some dissimilarities in collagen formation mechanisms between mation mechanism, see Figures S2 and S3. As described above, the
them. Because the collagen stimulation effect of PLLA is not imme- early-­stage volume effect of PDLLA is “resolving partially a few days
diate, after the mechanical distension of the suspension is resolved, after injection, followed by maintaining in the following months”
the mechanism of action enables the product to gradually restore (Figure 2).
volume.1 However, we have an interesting finding that the volume Our clinical findings are compatible with these mechanisms.
restoration with PDLLA seems immediate after the mechanical dis- However, the amount of volume induced by a biostimulator depends
tension of the suspension is resolved. To explain this phenomenon, on various patients' tissue responses in producing neo-­tissues. The
we elaborate on and illustrate the PDLLA collagen formation mecha- individual differences can be enormous. Besides, Figure 2 was plot-
nism. Based on the mechanism of action, we compare and discuss ted according to our clinical observations. If we had a series of three-­
the early stage volume effect difference between these two identi- dimentional photographs, we could calculate the volume change
cal biostimulators. and plot these volume/time curves more precisely. Further studies
There are some composition differences between injectable should be designed to investigate the influence factors and measure
PLLA and PDLLA. One vial of injectable PLLA contains 150 mg of the volume of neo-­tissues formation with different biostimulators.
solid PLLA microparticles, whereas one vial of injectable PDLLA con-
tains 154 mg of porous PDLLA microspheres (Figure S1). 2,3 The col-
lagen formation mechanism of PLLA has been well-­studied.1 When
mechanical distension from the suspension of the microparticles
resolves a few days after PLLA injection, the residual volume comes
from PLLA microparticles. Because the density of poly-­lactic acid is
between 1.25 and 1.36 g/ml,5 the total volume of all the microparti-
cles is <0.12 ml. For this reason, the visible volume effect disappears
almost totally. The volume effect cannot be seen until several weeks
to months later, when collagen fibers around PLLA microparticles
accumulate gradually.1 As a result, the early-­stage volume effect of
PLLA is “resolving a few days after injection, followed by growing
gradually in the following months.”
Due to the high porosity property of PDLLA microspheres, 2–­4
F I G U R E 1 Schematic representation of volume difference
the total volume of all PDLLA microspheres is several folds higher
between the same weight of solid microparticles and porous
than PLLA microparticles (Figure 1). As a result, although mechan- microspheres. The total volume of the same weight of porous poly-­
ical distension from the suspension also resolves a few days after d,l-­lactic acid microspheres is several folds larger than that of solid
PDLLA injection, the volume effect still exist due to these large poly-­l-­lactic acid microparticles. (Artwork courtesy of Hyegyeong Jo)

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2022 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

1702 | 
wileyonlinelibrary.com/journal/jocd J Cosmet Dermatol. 2023;22:1702–1703.
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LETTERS TO THE EDITOR 1703

DATA AVA I L A B I L I T Y S TAT E M E N T

Data sharing is not applicable to this article as no new data were cre-
ated or analyzed in this study.

E T H I C S S TAT E M E N T
The authors confirm that the ethical policies of the journal, as noted
on the journal's author guidelines page, have been adhered to. No
ethical approval was required as this is a review article with no origi-
nal research data.

Jui-­Yu Lin MD1

Ju-­Peng Fu MD2
F I G U R E 2 Schematic representation of volume versus Nai-­Jen Hsu MD3
time curve after injection of the same vial(s) with the same Chuan-­Yuan Lin MD1
reconstitution water amount of injectable poly-­l-­lactic acid (PLLA)
and poly-­d,l-­lactic acid (PDLLA). The first day after injection, 1
Li-­An Medical Clinic, Taipei City, Taiwan
volume effect comes from the reconstitution water amount. 2
But this volume effect resolves gradually day by day because of Plastic and Reconstructive Surgery, Tri-­Service General
water absorption. Around 2 weeks after injection, most of the Hospital, Taipei City, Taiwan
3
reconstitution water and other ingredients (apart from PLLA and Nai Jen HSU Dermatological Clinic, Tainan City, Taiwan
PDLLA microparticles) are absorbed. At this period, the residual
volume effect comes from the total volume of PLLA or PDLLA
Correspondence
microparticles. About 1 month after injection, collagen fibers
Chuan-­Yuan Lin, Li-­An Medical Clinic, 4F, No. 267, Lequn 2nd
formation begins. It can last for several months. As a result,
the volume effect of injectable PLLA increases gradually in the Road, Zhongshan District, Taipei City 104452, Taiwan.
following months. However, because PDLLA microspheres provide Email: [email protected]
scaffolds for collagen fibers formation, the volume effect remains
the same in the following months. (This diagram is based on the ORCID
clinical observation of our hundreds of PLLA and PDLLA injection
Chuan-­Yuan Lin https://orcid.org/0000-0003-2306-478X
experience.)

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The authors want to give special thanks to Chia-­Ti Pan for her kindly 5. Farah S, Anderson DG, Langer R. Physical and mechanical proper-
assistance with manuscript editing; to Hyegyeong Jo and Tung-­ ties of PLA, and their functions in widespread applications-­a com-
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Dr. Lin J-­Y and Dr. Lin C-­Y are medical directors of REGEN Biotech.,
and medical consultants of Jiangsu Wuzhong Aesthetic Biotech. Dr.
Hsu N-­J is a speaker of Galderma and a medical consultant of Jiangsu S U P P O R T I N G I N FO R M AT I O N
Wuzhong Aesthetic Biotech. Dr. Fu J-­P has no conflict of interest to Additional supporting information can be found online in the
disclose. Supporting Information section at the end of this article.