Journal of Cosmetic and Laser Therapy

ISSN: 1476-4172 (Print) 1476-4180 (Online) Journal homepage: http://www.tandfonline.com/loi/ijcl20

Comparative effects of various absorbable threads

in a rat model

Jung Jin Shin, Tae Jun Park, Bo Young Kim, Chang Min Kim, Dong Hye Suh,
Sang Jun Lee, Hye-Rim Moon & Hwa Jung Ryu

To cite this article: Jung Jin Shin, Tae Jun Park, Bo Young Kim, Chang Min Kim, Dong
Hye Suh, Sang Jun Lee, Hye-Rim Moon & Hwa Jung Ryu (2018): Comparative effects of
various absorbable threads in a rat model, Journal of Cosmetic and Laser Therapy, DOI:
10.1080/14764172.2018.1493511

To link to this article: https://doi.org/10.1080/14764172.2018.1493511

Published online: 06 Jul 2018.

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JOURNAL OF COSMETIC AND LASER THERAPY
https://doi.org/10.1080/14764172.2018.1493511

Comparative effects of various absorbable threads in a rat model

Jung Jin Shina, Tae Jun Parka, Bo Young Kima, Chang Min Kima, Dong Hye Suhb, Sang Jun Leeb, Hye-Rim Moona,
and Hwa Jung Ryua
a
Department of Dermatology, Korea University College of Medicine, Seoul, Republic of Korea; bDepartment of Dermatology, Arumdaun Nara
Dermatologic Clinic, Seoul, Republic of Korea

ABSTRACT ARTICLE HISTORY

Background: Conventional procedures including botulinum toxin and filler injections have their Received 15 January 2018
limitations in improving deep wrinkles and decreasing tissue laxity, and possess the propensity for Accepted 21 June 2018
vascular accidents. Absorbable thread is a recently commercialized field, but there is little evidence KEYWORDS
on comparative superiority. Objectives: We observed the effects of polydiaxanone (PDO) threads Absorbable threads; skin
with different number of strands in relation to collagen production and histopathology in a rat rejuvenation; polydiaxanone;
model. Materials and methods: Dorsal skin of rat was divided into five different compartments and collagen changes
four different PDO threads and monofilament poly-lactic acid (PLA) thread were inserted. Tissue
samples were obtained at week 1, 2, and 12 after the procedure for histopathologic review and real-
time PCR for quantification of collagen. Results: Multiple PDO filaments produced more collagen at
2 weeks. Single-stranded PLA thread insertion resulted in more Col1α1 levels than the double PDO
thread and also showed the most Col1α3 production at week 2. The amount of collagen showed a
sharp decline at week 12. Histologic evaluation showed retained threads surrounded by fibrous
capsule-like structure at week 12. Conclusion: We were able to observe more collagen production in
multiple stranded PDO threads compared to a single strand and that increasing number of threads
leads to more collagen synthesis.

Introduction (2). Previous animal studies have shown that although poly-
diaxanone (PDO) threads result in increased collagen a single
Skin rejuvenation and antiaging has become a very popular
PDO filament is thin and rather weak in terms of effectiveness
aspect in the field of dermatology. There are numerous signs
(3). Multifilament threads were introduced in order to over-
to skin aging with the major culprits being loosening of the
come these limitations and deliver sustainable and improved
septum that divides fatty compartments and dermal collagen
outcomes. Kim et al. reported the use of multi-PDO scaffold
degeneration. Conventional nonsurgical procedures including
in rat, mini-pig models, and in humans to improve forehead
botulinum toxin and filler injections have their limitations in
wrinkles (4). However, even with the plethora of different
improving deep wrinkles and decreased tissue laxity, and
PDO thread preparations, including threads of different
possess the propensity for vascular accidents. Recent esthetic
lengths, numbers, and thickness, the comparative data is
manipulation has focused more on safety, ease of procedure,
lacking. We observed the effects of PDO threads with differ-
effectiveness, and lower risk for side effects. Thus, thread
ent number of strands in relation to collagen production and
lifting has become a common trend in the suspension of the
histopathology in a murine model.
facial skin and soft tissue. This technique suspends the sus-
tainable tissues, such as the malar fat pad and/or platysma.
Originally, nonabsorbable ‘cogged’ threads were used to max- Material and methods
imize the skin lifting effects but due to fear for foreign body
Thread
reactions, absorbable threads have been developed as an alter-
native. Absorbable thread is a recently commercialized field Different types of absorbable PDO threads (mono, bi, quad,
and the insertion effect on the skin tissue is not clearly under- spring) and monofilament poly-lactic acid (PLA) thread was
stood. Our previous study demonstrated that absorbable provided by the manufacturer (N-finders™, Seoul, South
thread results in improved skin texture with modest lifting Korea).
effect (1). Furthermore, there are various products being
advertised to be more effective, but there is little evidence
Rat
on their comparative superiority. There are also conflicting
reports that the lifting effect achieved with absorbable thread Ten 8-week-old Sprague Dawley (SD) rats were purchased
is merely a transient reaction due to edema and inflammation ((weight 200 g, Orient Bio Inc., Gyeonggi-do, South Korea).

CONTACT Hwa Jung Ryu dermhj@naver.com Department of Dermatology, Korea University Ansan Hospital, 123, Jeokgeum-ro, Danwon-gu, Ansan-si,
Gyeonggi-do, Korea
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/ijcl.
© 2018 Taylor & Francis Group, LLC
2 J. J. SHIN ET AL.

Thread insertion at the back of the rat was performed under structures are larger and more prominent in the threads
general anesthesia with intramuscular injection of alfaxalone of the multiple strands than those of single strand
and xylazine (0.10 ml/kg). After shaving, the dorsal skin of (Figure 1). Aggregation of inflammatory cells and fibroblast
each rat was divided into five different compartments and was found around PDO thread. Tissue reaction of inflam-
various threads were inserted into its respective position matory cells was more prominent at 2 weeks than at
after making a small incision. Tissue samples including the 12 weeks. These reactions decreased with time. On the
thread and the surrounding tissues were harvested through other hand, histiocytes and giant cells were found more at
punch biopsy for histological examination at 1, 2, and 12 weeks than at 2 weeks. Especially, these cells were more
12 weeks after the procedure. Tissue samples for hematoxylin frequently observed in the quadruple thread.
and eosin (H&E) staining microscopy analysis were immedi-
ately fixed in 10% formalin. Samples for Col1A1, Col3A1, and
TGF-b1 quantification were embedded in optimal cutting
temperature embedding medium (Tissue-Tek OCT
Compound Miles, Naperville, IL) and immediately frozen
using liquid nitrogen and stored at −80°C.
This animal experiment was granted approval by the Korea
University Institutional Animal Care and Use Committee and
was conducted according to the Guide for the Care and Use of
Laboratory Animals provided by the Animal Laboratory Ethics
Committee of the Department of Laboratory Animal Medicine,
Medical Research Center, Korea University College of Medicine.
This animal experiment was approved by the Korea
University Institutional Animal Care and Use Committee
and the approval number is KUIACUC-2015-109.

Histologic analysis
Sample tissues were transversely sectioned along the thread
axis and stained using H&E to observe changes surrounding
the inserted thread.

Real-time RT-PCR
Total RNA from the sample tissue was extracted using
TriReagent (Thermo Fisher Scientific), and cDNA was
synthesized using Transcriptor First Strand cDNA Synthesis
Kit (Roche) with random hexamer. These cDNA samples
were then analyzed using SYBR Green on the Roche Cycler
480 II. All PCR primers for Col1α1 (collagen type 1), Col3α1
(collagen type 3), and TGF-β1 (transcription growth factor)
were followed: COL1α1, F: 5ʹ-CCTGCTGGTGAGAAAGG
ATC-3ʹ, R: 5ʹ-TCCAGAAGGACCTTGTTTGC-3ʹ; COL3α1,
F: 5ʹ-AGTCTTATCAGCCCTGATGG-3ʹ, R: 5ʹ-CTTGGTTA
GGATCAACCCAG-3ʹ; TGF-β1, F: 5ʹ-CAGTGGCTGAACCA
AGGAGA-3ʹ, R: 5ʹ-CTCGACGTTTGGGACTGATC-3ʹ.
Amplification conditions were: initiation at 95°C for 5 min,
followed by 45 cycles of 95°C for 10 s, 60°C for 10 s, and 72
for 10 s. Following amplification, melting curve analysis was
performed from 50°C to 105°C, reading every 0.5°C.

Results
Biopsy findings: histopathology features of PDO, PLA
thread
Histopathologic study revealed a foreign-body granuloma-
tous reaction surrounding exogenous material. In histologic
finding after PDO thread insertion, fibrous capsule like-
structures were observed around the thread. Capsular
Figure 1. Histologic finding of single, double, quadruple PDO. In the specimens
obtained 2 weeks after the insertion of thread, the thread of each single, double,
and quadruple PDO was well observed with the structure maintained (A, C, E).
The structure was well maintained after 12 weeks of insertion of the thread, but
the surrounding inflammatory reaction was decreased, and histiocyte and giant
cells were observed more frequently. (B, D, F), (A–F; hematoxylin and eosin x100,
scale bar: 100 μm).
 JOURNAL OF COSMETIC AND LASER THERAPY 3

Similar histologic changes were also observed after PLA
thread, PDO-spring insertion (Figures 2 and 3). Each thread
and its capsule structure was clearly observed and well main-
tained for up to 12 weeks without structural deformation.
Inflammatory cells were easily seen at 2 weeks, but decreased
at 12 weeks. As was the cases with the PDO threads, giant cells
and histiocytes increased at 12 weeks.
PDO-spring thread which is made by twisted thread was
expected to have a better effect due to a large amount of
thread per surface area, but the formation of collagen was
less than that of single, double, quadruple PDO thread.
The use of multiple-twisted thread increased the instant
formation of collagen. Also PLA component was used.
Despite of being monofilament, the formation of collagen in
PLA thread was found more than that in PDO double thread.

Collagen changes
The authors measured the amount of collagen synthesized by
tissue samples. As the number of strands increases in all
threads, the formation of collagen type I was also found to
increase. However, the formation of collagen was maximal at
2 weeks, and the amount of collagen at 12 weeks was lower
than that at 2 weeks (Figure 4).
Discussion
Nonabsorbable thread was the mainstay during the first intro-
duction of thread lifting, but since then, the fear for side
effects due to its permanency has resulted in the shift to
using absorbable threads. PDO is a synthetic monofilamen-
tous polymer which is completely absorbed by simple

Figure 2. Histologic finding of PLA. (G) PLA is well found in a 2-week specimens. (H) The reduction of inflammatory cells is clearly observed with the PLA structure
maintained in a 12-week specimens (G–H; hematoxylin and eosin x100, scale bar: 100 μm).

Figure 3. Histologic finding of PDO-spring. (I) PDO-spring is well found in a 2-week specimens. (J) Histiocytes and giant cells with PDO-spring are observed at
12 weeks. (I–J; hematoxylin and eosin x100, scale bar: 100 μm).
4 J. J. SHIN ET AL.
Figure 4. The amount of collagen synthesis according to the type of thread measured at 1, 2, and 12 weeks.
hydrolysis in about 180 days. Low tissue reactivity and pro-
longed tensile strength has garnered preference over others in
the use for thread lifting (5,6). Insertion of single PDO thread
over multiple sessions has been the basis for wrinkle correc-
tion. Increasing popularity of “lunch time” lifting has resulted
in a search for the optimal combination of thread and inser-
tion methods to maximize lifting effects in shorter down time
(7). In order to meet this demand, several studies have looked
at the effects of different threads under the skin to search for
materials and formulations that result in sustained outcomes
(3,4,8). Various types of threads have been introduced: uni-/
bidirectional cogged, gold-coated, mesh, braided, and also of a
spring form, but there is a lack of evidence on increased
effectiveness (9–11).
Our results showed that multiple PDO filaments produced
more collagen (Col1α1, Col1α3) at 2 weeks after insertion.
Although the increment was not in multiples as with the
number of strands, multiple PDO intertwined together
resulted in more collagen production. Ironically, spring type
PDO suspension, designed to maximize fiber amount per unit
area, showed the least collagen production. One explanation
would be due to the uneven distribution of the spring thread
under the rat skin. Considering the elastic property and the
substantial resistance during insertion, the spring may have
not achieved thorough distribution compared to the linear
threads. In regards to ease of manipulation, monofilament
thread insertion was smoother and rather straightforward
after puncture, while thicker strands were more challenging.
Hypothetically, multi-braided threads will offer increased ten-
sile strength and decreased absorption rate. However, there
are risk-benefits, as more number of thread intertwined will
lead to a substantial increase in diameter, and the wider
puncture entrance may subsequently lead to increased source
of infection and scar formation (11).
In the comparison between PDO and PLA threads, single-
stranded PLA thread not only resulted in more Col1α1 levels
than the double PDO thread but also showed the most Col1α3
production at 2 weeks. PLA is another popular dermal filler
material and induces bio-stimulatory effect by capsule forma-
tion orchestrating macrophages, fibroblasts, and collagen (12).
The degradation time of PLA into water and carbon dioxide
ranges from 9 to 30 months, which is longer than the 6-
month duration reported for PDO (13,14). Whether this
prolonged degradation time is responsible for the increased
production of collagen needs to be seen through further
studies.
Histologic evaluation (figures A-J) showed retained threads
surrounded by fibrous capsule-like structure at 12 weeks post-
insertion. Savoia et al. analyzed skin biopsy samples and
ultrasonography images after procedure using absorbable

thread and observed homogenous fibrous capsule formation
along the thread, as well as increased dermal thickness and
vascular structures (8). Many have also previously reported
observation of aggregated inflammatory cells, fibroblasts, and
collagen in the surrounding capsule, so in this study we did
not evaluate the exact composition (3,4,8–10). Regardless, the
multi-PDO threads showed larger surrounding capsules and
should likely induce more space filling effect and function as a
reservoir for collagen synthesis (3,4).
However, despite the presence of the thread and sur-
rounding capsules, collagen levels showed a sharp decline at
12 weeks. This result is somewhat contrary to previous
reports by Kim et al. (4), where multi-PDO scaffold on
rats showed sustained collagen synthesis up to 12 weeks
after insertion. An explanation for this discrepancy would
be that the multi-scaffold PDO used had a stent like
appearance and had far more filaments braided (16) than
the ones used in our study (at most 4). Chung et al. (3)
showed increased collagen levels lasting up to 7 months
using barbed mono-PDO threads, but it was an experiment
in guinea pigs. In studies by Jang et al. (9) and Yoshimura
et al. (10), the greatest tensile strength and thickest capsule
diameter was observed at 4 weeks, although the thread
material used was not absorbable. Based on these results,
collagen formation may have peaked and was on the
decline before the 12th week in our study. There is a
need for more concrete data from subsequent studies to
elucidate the direct relationship between collagen synthesis
and capsule thickness.
The limitation of our study is the small number of
animals sacrificed. We also did not evaluate in detail on
the composition of the capsule surrounding the thread,
which would have made comparison among the different
thread materials possible with more discretion. In addition,
whether the results are consistent in clinical practice is
unknown. Furthermore, there is a need to consider the
difference in skin properties of human and murine model
and that the effects may vary. Finally, different insertion
techniques may give various results.
Conclusion
In this study, we were able to observe more collagen production
in multiple stranded PDO threads compared to a single strand
and that increasing the number of threads leads to more collagen
synthesis. Collagen production was at the peak 2 weeks post-
insertion and even at 3 months, the levels were still increased.
Mono-PLA threads showed better results than mono-PDO
threads while spring formation of PDO was the least effective.
Overall, appropriate selection of thread type, diameter, shape,
and insertion technique will all factor into obtaining optimal
thread lifting results. We believe our findings will serve us a basis
for producing threads that are more effective in the near future.
JOURNAL OF COSMETIC AND LASER THERAPY 5
Acknowledgments
This study was technically supported by the Core Laboratory for
Convergent Translational research in College of Medicine, Korea
University. The threads were provided by N-finders.
Funding
None.
Conflicts of interest
None declared.
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