Original Article

Cosmetic
Reconstitution of Injectable Poly-d,l-lactic Acid:
Efficacy of Different Diluents and a New
Accelerating Method
Se-Yi Chen, MD*†

Szu-Ting Chen, PhD‡ Background: Injectable poly-d,l-lactic acid (PDLLA) is a new collagen-stimulating
Jui-Yu Lin, MD§ filler containing PDLLA microspheres and carboxymethyl cellulose. It is available
Chuan-Yuan Lin, MD§ as a lyophilized powder that must be reconstituted with a diluent before adminis-
tration. The aims of this study were to investigate the efficacy of different diluents
and a new accelerating “back-and-forth” method.
Methods: Six different diluents, sodium bicarbonate, sterile water for injection
(SWFI), normal saline, lidocaine, lidocaine with epinephrine (lidocaine + E), and
mannitol, were tested. The recommended “vortex” method for preparation of thin
suspensions and a new back-and-forth method suitable for both thin and thick
suspensions were compared. Gross and microscopic views of the prepared suspen-
sions were examined.
Results: Using the vortex method, only mannitol and SWFI are found to be effective
reconstitution diluents for injectable PDLLA. Using the back-and-forth method,
all six diluents can be used for reconstitution of injectable PDLLA. Moreover, the
time needed for reconstitution of injectable PDLLA by this back-and-forth method
is very short, regardless of the thickness of the suspension.
Conclusions: Clinically, only SWFI can be used for reconstitution of injectable
PDLLA by “hand-shaking” or vortex method. To accelerate the reconstitution
time especially when using small amount of SWFI, back-and-forth is the method
of choice. Besides, when SWFI is not available, other diluents such as nor-
mal saline, lidocaine, or lidocaine + E can be used by this novel back-and-forth
reconstitution method. (Plast Reconstr Surg Glob Open 2020;8:e2829; doi: 10.1097/
GOX.0000000000002829; Published online 18 May 2020.)

INTRODUCTION and injectable poly-d,l-lactic acid (PDLLA). Injectable

Over the past decade, injectable fillers have become PLLA (Sculptra; Galderma, Fort Worth, Tex.)5,7–12 contains
popular agents for soft tissue contouring and volumizing.1 PLLA, carboxymethyl cellulose (CMC), and mannitol,
Among them, injectable poly-lactic acid is the so-called while injectable PDLLA (AestheFill; REGEN Biotech, Inc.,
collagen-stimulating filler.2–7 Two injectable poly-lactic acid Seoul, South Korea)6,13–17 contains PDLLA and CMC. Both
fillers are available: injectable poly-l-lactic acid (PLLA) fillers are available in vials as a lyophilized powder, and
reconstitution with a diluent before injection is required.
The reconstitution method used for injectable PLLA
From the *Department of Neurosurgery, Chung-Shan Medical has been extensively discussed and modified over the past
University Hospital, Taichung, Taiwan, Republic of China; 2 decades since its first approval in Europe. Proper recon-
†School of Medicine, Chung-Shan Medical University, Taichung, stitution of injectable PLLA is a critical factor in reduc-
Taiwan, Republic of China; ‡Institute of Clinical Medicine, ing complications such as papules and nodules formation
National Yang-Ming University, Taipei, Taiwan, Republic of after injection.7,9–12
China; and §Tobeauty Aesthetic Clinic, Taipei, Taiwan, Republic Injectable PDLLA was initially approved by the Korean
of China. Food and Drug Administration in 2014. A vial of inject-
Received for publication December 3, 2019; accepted March 6, able PDLLA contains 200 mg of lyophilized powder. The
2020. PDLLA microparticles are spherical in shape, spongiform
Copyright © 2020 The Authors. Published by Wolters Kluwer Health, in consistency, and 30–70 μm in size.6,16,17 The suggested
Inc. on behalf of The American Society of Plastic Surgeons. This
is an open-access article distributed under the terms of the Creative Disclosure: Dr. Jui-Yu Lin and Dr. Chuan-Yuan Lin are
Commons Attribution-Non Commercial-No Derivatives License 4.0 medical directors of REGEN Biotech. Dr Se-Yi Chen and Szu-
(CCBY-NC-ND), where it is permissible to download and share the Ting Chen have no conflicts of interest to disclose. Injectable
work provided it is properly cited. The work cannot be changed in poly-d,l-lactic acid tested in this experiment was provided by
any way or used commercially without permission from the journal. REGEN Biotech.
DOI: 10.1097/GOX.0000000000002829

www.PRSGlobalOpen.com 1
 PRS Global Open • 2020

diluent for reconstitution is sterile water for injection suspension became grossly homogenous or after a maxi-
(SWFI). However, can we use a diluent other than SWFI mum agitation time of 30 minutes. We then observed the
for reconstitution? According to the instructions for use, distribution of PDLLA microspheres microscopically. The
for shallow lines or overall facial wrinkle correction, 8 mL tubes were then allowed to stand for 30 minutes before
SWFI is used to reconstitute one vial of injectable PDLLA 0.1 mL lidocaine solution (both lidocaine and lidocaine
by shaking (“hand-shaking” method) until the SWFI is + E were used in different experiment groups) was added
well mixed with the lyophilized powder; for deep wrinkle to the SWFI and mannitol tubes. The resultant mixtures
correction, 1.4 mL SWFI is used to reconstitute one vial were then agitated by hand-shaking followed by gross and
of injectable PDLLA by agitation assisted by the vortex microscopic observations. The 6 suspensions were exam-
generator (“vortex” method).6,15 However, when 8  mL ined again after 24 and 48 hours. All these experiments
SWFI is used, more than 30 minutes is usually required were repeated 5 times.
for total dissolution by the hand-shaking method, and
it is an exhausting process. Agitation assisted by the vor- Back-and-forth Method
tex method is helpful. When 1.4 mL SWFI is used, more One injectable PDLLA bead was placed in a 3-mL
than 1 hour is required to achieve full dissolution by the syringe. Another 3-mL syringe was used to retrieve the
vortex method. Therefore, we developed a novel “back- required volume of diluent to prepare a thin or thick sus-
and-forth” method that can accelerate the reconstitution pension. The 2 syringes were tightly connected with a 3-way
procedure of injectable PDLLA. stopcock by Luer-lock (Fig. 1). The diluent and injectable
The objectives of this study were to investigate the PDLLA were then pushed back-and-forth between these 2
efficacy of different diluents and this new back-and-forth syringes for 1 minute, and the resultant suspensions were
method in the reconstitution of injectable PDLLA. The injected into Eppendorf tubes. Gross and microscopic
critical step in the reconstitution of injectable PDLLA is to observations were performed immediately and again after
dissolve all the CMC particles and prevent CMC particle 30 minutes, 24 hours, and 48 hours. All these experiments
aggregation. Some dissolution properties of CMC relevant were repeated 5 times.
to this study are discussed in this article.
RESULTS
MATERIALS AND METHODS
Diluents Characteristics
Materials NaHCO3 is a weakly alkaline diluent; SWFI, lidocaine,
The injectable PDLLA used in this study was and mannitol are neutral diluents; and NS and lidocaine
AestheFill-V200, which comprises 13–15 acorn-shaped + E are acidic diluents. All 6 diluents contain SWFI as their
lyophilized powder beads of total weight 200 mg stored in excipient. NaHCO3, NS, lidocaine, and lidocaine + E con-
a vial. Six different diluents, namely SWFI, normal saline tain dissolved electrolytes in their ingredients, but SWFI
(NS), lidocaine, lidocaine with epinephrine (lidocaine + and mannitol do not. Therefore, the ionic strength of
E), sodium bicarbonate (NaHCO3), and mannitol, were NaHCO3, NS, lidocaine, and lidocaine + E is high, whereas
chosen for reconstitution tests. that of SWFI and mannitol is low. The characteristics of
these diluents are listed in Table 1.
Methods
The pH value of each diluent was measured using a pH Vortex Method
meter. As recommended by the manufacturer, 2 suspen- After immersing the PDLLA beads into each of the
sion “concentrations” can be prepared by reconstitution: diluents for 3 minutes, only the beads in SWFI and man-
200 mg injectable PDLLA per 8 mL (a “thin” suspension) nitol showed signs of dispersion, with mannitol effecting
or 1.4 mL (a “thick” suspension) diluent.15 The weight of slightly a better dispersion than SWFI. The beads in the
each lyophilized powder bead of injectable PDLLA was
measured and then the corresponding volume needed to
prepare a thin or thick suspension was calculated. Using
the 6 aforementioned diluents, thin suspensions were pre-
pared by the vortex method, whereas both thin and thick
suspensions were prepared by the back-and-forth method.

Vortex Method
One acorn-shaped bead of injectable PDLLA was
placed in a 2-mL Eppendorf tube followed by the vol-
ume of diluent needed to prepare a thin suspension. The
dissolution pattern over the first 3 minutes after immer-
sion of the PDLLA bead was recorded for each diluent.
With these tubes holding on fingers, they were agitated
by touching on the vibrated platform of a vortex gen-
erator at 2,700 rpm. We inspected the suspension every Fig. 1. Back-and-forth method: 2 syringes, each containing a diluent
5 minutes and stopped the agitation process after the and a PDLLA bead, were tightly connected with a 3-way stopcock.

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Chen et al. • Reconstitution of Injectable PDLLA

Table 1. Diluents’ Characteristics

NaHCO3 SWFI NS Lidocaine Lidocaine + E Mannitol
Trade name SOD. Water for Normal saline Xylocaine 2% for Lidophrine Maniton
BICARBONATE injection solution “TBC” intravenous
INJ. injection
Manufacturer Chi Sheng Sintong Taiwan Sintong Taiwan Cenexi Oriental Chemical Shinlin Sinseng
Chemical Cor. Biotech Co., Biotech Co., Ltd Works, Inc. Pharmaceutical
Ltd
Main ingredient NaHCO3 NaCl Lidocaine HCl Lidocaine HCl, d-Mannitol
epinephrine
Other ingredients NaCl, HCl, C8H8O3, NaCl, Na2S2O5,
NaOH CH3COONa
Na3PO4, C3H8O2,
CH3COOH, NaOH
Excipient SWFI SWFI SWFI SWFI SWFI SWFI
Ionic strength High Low High High High Low
pH 8.5 6.8 5.5 6.8 4.2 6.5
C3H8O2, propylene glycol; C8H8O3, methyl paraben; CH3COOH, acetic acid; CH3COONa, sodium acetate; HCl, hydrochloride; NaCl, sodium chloride; NaOH,
sodium hydroxide; Na3PO4, sodium phosphate tribasic; Na2S2O5, sodium metabisulfite; TBC, Taiwan Biotech Co.

other 4 diluents showed no signs of dispersion after this between the pH values of these diluents and their effec-
time period (Fig. 2). tiveness at reconstituting injectable PDLLA. No further
After observation, the tubes were then agitated by a changes were found after adding lidocaine (or lidocaine
vortex generator at 2,700 rpm. After 5 and 10 minutes, the + E) into reconstituted suspension and after 24–48 hours.
mannitol and SWFI tubes contained homogenous suspen-
sions, respectively. After 30 minutes, the agitation process Back-and-forth Method
was stopped for the other 4 tubes. Although they showed
a good suspension, the suspended particles in these tubes Thin Suspension
were larger than those in the mannitol and SWFI tubes All diluents resulted in homogenous suspensions after
(Fig. 3). using the back-and-forth method (Fig. 6). The prepared
The suspensions in the 6 tubes were then examined suspensions remained homogenous without floating par-
microscopically. The mannitol and SWFI tubes contained ticles or precipitation even after standing for 30 minutes
well-separated microspheres, whereas the other 4 tubes (Fig.  7), 24 hours, and 48 hours. The microspheres of
contained aggregates comprising tens to hundreds of injectable PDLLA were well separated in the 6 different
microspheres (Fig.  4). Gross and microscopic images diluents both immediately and at 30 minutes after prepa-
did not change significantly after adding lidocaine (or ration using the back-and-forth method (Fig. 8).
lidocaine + E) solution to the SWFI and mannitol tubes.
After standing for 30 minutes, only the SWFI and man- Thick Suspension
nitol tubes retained homogenous suspensions; the other All suspensions exhibited a paste-like appearance after
4 tubes contained 2 distinct layers with particles floating using the back-and-forth method, which remained for 30
on the diluent (Fig. 5). No further gross or microscopic minutes, 24 hours, and 48 hours. Microscopic examina-
changes were observed in any of the 6 tubes after 24 and tion of the suspensions revealed that, despite being close
48 hours. together due to the high concentration, the microspheres
Of the 6 diluents tested here, only 2 diluents with low were well separated in all 6 different diluents both imme-
ionic strength, SWFI and mannitol, were found to be effec- diately and 30 minutes after preparation using the back-
tive diluents for reconstitution of injectable PDLLA using and-forth method (Fig. 9).
the vortex method. The reconstitution time was shorter By using the back-and-forth method, all 6 diluents can
for mannitol than that for SWFI. No correlation was found be used for reconstitution of injectable PDLLA quickly

Fig. 2. Three minutes after immersing the PDLLA beads into 1 of the Fig. 3. Right after the vortex method, the 6 diluents yielded homog-
6 diluents, only SWFI and mannitol tubes showed signs of dispersion. enous suspensions.

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Fig. 4. After homogenous suspensions were attained, only the mannitol and SWFI tubes contained fully separated microspheres, whereas
the other 4 tubes contained microspheres stuck together in groups. A, Sodium bicarbonate; B, sterile water for injection; C, normal saline;
D, lidocaine; E, lidocaine + E; F, mannitol (original magnification ×50).

Fig. 5. Standing for 30 minutes after the vortex method, only the Fig. 6. All tubes contained homogenous suspensions right after
SWFI and mannitol tubes retained homogenous suspensions, preparation using the back-and-forth method.
whereas the other 4 tubes exhibited 2 distinct layers with particles
floating on the diluents.
liquid, called the diluent, before it can be administered. In
this experiment, we chose SWFI, NS, lidocaine, lidocaine
and effectively, regardless of the thickness of the desired + E, NaHCO3, and mannitol as diluents for the reconstitu-
suspensions. tion test. The reasons why we choose these diluents are
described below. SWFI is the diluent recommended by the
DISCUSSION manufacturer.15 NS is readily available and is the diluent
used for the reconstitution of botulinum toxin.24 It is the
Injectable PDLLA must be stored in powdered form
diluent that is most often used to replace SWFI for the
because PDLLA gradually decomposes into lactic acids via reconstitution of injectable PLLA.25 Lidocaine and lido-
hydrolysis,18–22 and the CMC hydrogel undergoes hydro- caine + E solutions are the diluents used for the reconsti-
lytic degradation.23 The PDLLA microspheres are pre- tution of the acellular dermal matrix.26 They are also often
pared by a new solvent spray technique,4 suspended in added to the suspension after reconstitution of injectable
CMC solution, and then lyophilized into powdered form. PDLLA with SWFI for anesthesia. NaHCO3 can be added
The powdered form needs to be reconstituted with a to the lidocaine solutions to adjust their pH to reduce

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Chen et al. • Reconstitution of Injectable PDLLA

the second is to separate all the PDLLA microspheres, and

the third is to disperse the PDLLA microspheres homog-
enously in the solution. Because PDLLA microspheres
are spherical in shape and spongiform in consistency,17
they can be separated and dispersed easily in a solution.
Therefore, the critical step in the reconstitution of inject-
able PDLLA is to dissolve all the CMC particles and pre-
vent CMC particle aggregation.
CMC was first prepared in 1918 and was produced
commercially in the early 1920s.29,30 It readily dissolves in
hot or cold water to form viscous, transparent solutions
Fig. 7. All suspensions prepared by the back-and-forth method
with a range of thickening, dispersing, gelling, stabiliz-
remained homogenous without floating particles or precipitation
after standing for 30 minutes.
ing and film-forming properties, with many applications
in the food, cosmetics, pharmaceutical, and detergents
industries.30,31 CMC gel is present in several commercially
pain on injection.27 It is the only alkaline diluent used in available subdermal fillers such as Laresse (FzioMed, Inc.,
this test. It was included in this study not for the purpose San Luis Obispo, Calif.),31,32 Radiesse (Bioform Medical,
of clinical use but to check whether the pH value of the Inc., San Mateo, Calif.),33 and Ellanse (AQTIS Medical BV,
diluent exhibits any correlation with the ease of recon- Utrecht, The Netherlands)34 as filling or carrier. These
stitution. Mannitol, a naturally occurring sugar alcohol products containing CMC gel were supplied as prefilled
used clinically for its osmotic diuretic properties,28 is one syringes that were ready for immediate use. For injectable
of the ingredients of injectable PLLA. It was included in PDLLA that requires reconstitution before administra-
this study not for the purpose of clinical use but to check tion, the dissolution properties of CMC play an important
whether mannitol has any effect on the reconstitution of role in the reconstitution process. CMC is produced by
injectable PDLLA. partially substituting the hydroxyl groups on the cellulose
The goal of reconstitution is to obtain a homogenous backbone with carboxymethyl groups, and this carboxy-
suspension without any PDLLA microsphere aggregates. methylation is what makes CMC water-soluble.30 The disso-
There are 3 steps in the reconstitution of injectable lution process comprising mechanical stirring, agitating,
PDLLA. The first is to dissolve all the solid particles of and pumping or shearing is a necessary step to create CMC
CMC into a solution without CMC particle aggregation, solutions.35 When it dissolves in water, the nonsubstituted

Fig. 8. The PDLLA microspheres in the thin suspension prepared by the back-and-forth method were fully separated in each of
the 6 different diluents immediately after reconstitution. A, Sodium bicarbonate; B, sterile water for injection; C, normal saline;
D, lidocaine; E, lidocaine + E; F, mannitol (original magnification ×50).

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 PRS Global Open • 2020

each other by mannitol before entering the liquid, thereby

minimizing aggregation.41 However, there is a scarcity of
published information detailing the role of NS and man-
nitol in injectable PLLA. Further study on the interaction
among NS, mannitol, and injectable PLLA is needed.
Clinically, it is not practical for us to choose mannitol as
a reconstitution diluent for injectable PDLLA. Therefore,
only SWFI can be effectively used as a reconstitution dilu-
ent for injectable PDLLA by the vortex or hand-shaking
method.
The back-and-forth method has been used to mix some
fillers,26,42 with lidocaine for anesthesia or as a carrier. In
these previous methods, only simple mixing of drugs was
required, and 2 syringes were connected by a coupler or
connector with a large through hole. The purpose of the
back-and-forth method used here was to completely dis-
solve and disaggregate the CMC particles. Because CMC
exhibits shear-thinning, a dissolution process involving
mechanical stirring, agitation, pumping, or shearing is
necessary. The 3-way stopcock has a small through hole,
Fig. 9. The PDLLA microspheres in the thick suspension prepared around 2 millimeters in diameter. When we performed
by the back-and-forth method were crowded, but still separately the back-and-forth reconstitution process, the flow veloc-
distributed, in each of the 6 different diluents. This image was taken
ity of the solution when it passed through this small
from the SWFI tube (original magnification ×50).
through hole was extremely high. This induced a strong
solution jet, which resulted in swirls and turbulence inside
hydroxyl groups remaining in the CMC molecules may one syringe. This situation occurred inside both syringes
interact in a very specific manner by intramolecular and/ alternatively throughout the back-and-forth process. As a
or intermolecular hydrogen bonding, and this interaction
result, the CMC particles could dissolve and disaggregate
leads to the formation of aggregates or associates that can
in a very short time, regardless of the ionic strength of
be significantly influenced by the solvent.35,36 CMC solu-
the diluents. This process also led to completely separated
tions are sensitive to variations in pH and ionic strength,
and homogenously dispersed PDLLA microspheres.
but the ionic strength of the solution has more influence
The advantages of this method are not only that it is
on the conformation of CMC than the pH.37–40
quick and can be used for reconstitution with various dilu-
With the 3 methods described in this test, the shear-
ent, but it is also easier to obtain a thick suspension that
ing force generated from the back-and-forth method is
is difficult to achieve using the vortex method. Clinically,
the strongest, whereas that of the vortex and hand-shak-
ing methods is moderate. Of the 6 diluents studied here, when we perform reconstitution of one vial of injectable
only NaHCO3 is alkaline, and the others are neutral or PDLLA (13–15 acorn shape beads), the syringes used were
acidic. However, NaHCO3 did not result in better CMC 10 mL instead of 3 mL. The time needed for the back-and-
dissolution than the other diluents. As mentioned above, forth process is about 5 minutes, regardless of whether
the ionic strength of the solution has a greater influence 8 mL or 1.4 mL SWFI is used. However, a disadvantage of
on the conformation of CMC than pH value. When high this method is the need to transfer PDLLA beads from
ionic strength solutions (NS, lidocaine, lidocaine + E, and the vial into the syringe, during which the chances of con-
NaHCO3) were used, the CMC particles easily aggregate. tamination increase and accidental spilling of the PDLLA
This causes aggregation of PDLLA microspheres because beads may happen. Therefore, this procedure should be
they adhere to CMC particles. When the vortex method performed by a well-trained professional under strict asep-
is used for reconstitution, these aggregations cannot be tic conditions. Although we did not encounter complica-
disaggregated because the shearing force is not strong tions such as infection, nodule, or granuloma formation
enough. On the contrary, when high shearing force back- using this back-and-forth reconstitution method in our 2
and-forth method is used, they become disaggregated and years’ clinical experience, we seldom used diluents other
result in a homogenous suspension in a short time. than SWFI for the reconstitution of injectable PDLLA.
Interestingly, the time required for dispersion of the One of the limitations of this study is that the experiments
PDLLA microspheres was shorter for mannitol than for performed were in vitro experiments. Understanding
SWFI tube by the vortex method. This result implies that whether using this new back-and-forth reconstitution
mannitol is a solubilizer of CMC. Besides, NS cannot method with diluents other than SWFI can lead to an
be used as a diluent for injectable PDLLA by the vortex effect that is comparable to the effect achieved using the
method but can be used for injectable PLLA.25 This may traditional vortex or hand-shaking reconstitution method
be due to the pre-blending effect of CMC and mannitol. with SWFI after injectable PDLLA administration still
By pre-blending, the CMC particles are separated from requires further controlled studies in vivo.

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Chen et al. • Reconstitution of Injectable PDLLA

CONCLUSIONS 9. Lorenc ZP, Greene T, Gottschalk RW. Injectable poly-L-lactic

CMC possesses interesting dissolution properties. A dis- acid: understanding its use in the current era. J Drugs Dermatol.
solution process of CMC that involves shearing force is nec- 2016;15:759–762.
10. Vleggaar D, Fitzgerald R, Lorenc ZP. The history behind the
essary. The shearing force generated by different methods
use of injectable poly-L-lactic acid for facial and nonfacial volu-
from high to low is back-and-forth, vortex, and hand-shaking mization: the positive impact of evolving methodology. J Drugs
method, respectively. The conformation of CMC particles Dermatol. 2014;13(4 Suppl):s32–s34.
will also be affected by the ionic strength of the diluent. The 11. Alessio R, Rzany B, Eve L, et al. European expert recommenda-
ionic strength of NS, lidocaine, lidocaine + E, and NaHCO3 tions on the use of injectable poly-L-lactic acid for facial rejuve-
is larger than that of SWFI and mannitol. When high nation. J Drugs Dermatol. 2014;13:1057–1066.
ionic strength solutions (NS, lidocaine, lidocaine + E, and 12. Vleggaar D, Fitzgerald R, Lorenc ZP, et al. Consensus rec-
NaHCO3) were used, CMC particles easily aggregate. These ommendations on the use of injectable poly-L-lactic acid for
CMC particle aggregations cannot be separated totally by facial and nonfacial volumization. J Drugs Dermatol. 2014;13(4
less powerful shearing force vortex method. Therefore, only Suppl):s44–s51.
13. Hyun MY, Lee Y, No YA, et al. Efficacy and safety of injection with
SWFI and mannitol can be used in this method. On the con-
poly-L-lactic acid compared with hyaluronic acid for correction
trary, when using the back-and-forth method, all these dilu-
of nasolabial fold: a randomized, evaluator-blinded, comparative
ents can be used for the reconstitution of injectable PDLLA study. Clin Exp Dermatol. 2015;40:129–135.
because the CMC particle aggregations can be separated 14. No YA, Seok J, Hyun MY, et al. Long-term (24-month) safety
totally by a more powerful shearing force. evaluation of poly-DL-lactic acid filler injection for the nasolabial
Clinically, only SWFI can be used by the hand-shak- fold: a multicenter, open, randomized, evaluator-blind, active-
ing or vortex reconstituted method. The back-and-forth controlled design. Plast Reconstr Surg. 2015;135:1074e–1075e.
method is a good choice for quick reconstitution of inject- 15. AestheFill (Injectable Poly-D,L-lactic acid)[Instructions for Use]. Seoul,
able PDLLA. Moreover, when SWFI is not available, we can South Korea: REGEN Biotech, Inc; 2014.
use NS, lidocaine, or lidocaine + E as a diluent for recon- 16. Chen SY, Lin JY, Lin CY. Compositions of injectable poly-D,L-lac-
stitution of injectable PDLLA by this novel back-and-forth tic acid and injectable poly-L-lactic acid. Clin Exp Dermatol. 2020;
45:347-348.
method. However, further studies are needed to understand
17. Chen SY, Lin JY, Lin CY. Letter to the editor regarding the arti-
more about the clinical outcomes after the administration cle “Kwon T-R, Han SW, Yeo IK, et al. Biostimulatory effects of
of injectable PDLLA reconstituted using nonstandard dilu- polydioxanone, poly-d,l lactic acid, and polycaprolactone fillers
ents and the back-and-forth method proposed here. in mouse model. J Cosmet Dermatol. 2019;18(4):1002–1008.” J
Cosmet Dermatol. 2020;19:1004-1005.
Chuan-Yuan Lin, MD 18. Gonzalez MF, Ruseckaite RA, Cuadrado TR. Structural changes
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1F, No 18-1, Sanmin Rd tion. J Appl Polym Sci. 1999;71:1223–1230.
Songshan District, Taipei City 10582 19. Grizzi I, Garreau H, Li S, et al. Hydrolytic degradation of devices
Taiwan, Republic of China based on poly(DL-lactic acid) size-dependence. Biomaterials.
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