Journal of Cosmetic and Laser Therapy

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Granuloma as a complication of polycaprolactone-

based dermal filler injection: ultrasound and
histopathology studies

Ewa Skrzypek, Barbara Górnicka, Daisy Miriam Skrzypek & Mlosek Robert
Krzysztof

To cite this article: Ewa Skrzypek, Barbara Górnicka, Daisy Miriam Skrzypek & Mlosek
Robert Krzysztof (2018): Granuloma as a complication of polycaprolactone-based dermal filler
injection: ultrasound and histopathology studies, Journal of Cosmetic and Laser Therapy, DOI:
10.1080/14764172.2018.1461229

To link to this article: https://doi.org/10.1080/14764172.2018.1461229

Published online: 14 May 2018.

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JOURNAL OF COSMETIC AND LASER THERAPY
https://doi.org/10.1080/14764172.2018.1461229

Granuloma as a complication of polycaprolactone-based dermal filler injection:

ultrasound and histopathology studies
Ewa Skrzypeka, Barbara Górnickab, Daisy Miriam Skrzypekc, and Mlosek Robert Krzysztofd
a
Department of History of Medicine, Medical University of Warsaw, Warsaw, Poland; bDepartment of Pathology, Medical University of Warsaw,
Warsaw, Poland; cDepartment of Forensic Medicine, Medical University od Warsaw, Warsaw, Poland; dDepartment of Diagnostic Imaging of the II
Medical Faculty of the Medical University of Warsaw, Warsaw, Poland

ABSTRACT ARTICLE HISTORY

In aesthetic medicine, there has been an ongoing search for an ideal dermal filler to offer zero Received 10 October 2017
complication rate. Polycaprolactone-based dermal filler (PCL) has been available since 2009. Accepted 18 March 2018
The purpose of the paper was to present a case of granuloma as a complication of PCL injection,
KEYWORDS
which has not been reported so far by other researchers. A 68-year-old female was injected with PCL. Fillers; foreign body
One year later, nodules accompanied by bluish skin discoloration developed within the injection site. granuloma; high frequency
Ultrasound and histopathology studies were performed. The examinations confirmed the presence of ultrasound;
foreign body granuloma after PCL, which makes it the first reported case worldwide. The published data polycaprolactone
analyses showed general lack of studies and case reports to address this issue. The PCL, like an injection
of any soft tissue filler, may lead to serious complications, such as granuloma formation. This makes
further research legitimate and necessary.

The ideal dermal filler should be safe, biocompatible and
should not induce inflammatory response, while providing a
long-term (but not permanent), natural filling effect (1–3). It
should also be easy to remove from tissues in the event of
complications. Complications can be divided into early or
late, local or systemic (4,5). The polycaprolactone-based der-
mal filler (PCL) is a new class of biostimulatory dermal fillers
(6). It has been approved as a medical device and CE marked
in the UK for use in aesthetic dermatology in deep dermal and
subcutaneous implantation (7). So far, it is the only PCL
microsphere-based dermal filler (8,9). It acts by stimulating
neocollagenesis, which provides an aesthetic effect lasting for
1–4 years (5,8,10). The product is composed of PCL in 30%
and carboxymethylcellulose (CMC) in 70% (8). Both PCL and
CMC are widely used in bioresorbable sutures, implants,
especially in maxillofacial surgery or orthopaedics; in con-
trolled drug delivery vehicles; in wound care and aesthetic
medicine (9–11).
Material and method
A 68-year-old female was administered with Ellansé-MTM
(AQTIS Medical, Utrecht, The Netherlands). She had good
general health and her medical history was insignificant
otherwise. The procedure was performed in January 2013.
The filler was administered into nasolabial folds with 27G
needle as a deep subcutaneous injection using retrograde
linear threading technique. About 0.5 mL of filler was admi-
nistered onto each side of the face at that area. Fannig, cross-
hatching and microbolus (0.05 mL and 0.05 mL/bolus,
amounting to the total of 0.5 mL of filler administered onto
each side of the face) were used to correct marionette lines
and oral commissures. The procedure was uneventful. Follow
up assessments at 1 and 6 months were carried out.
The patient reported that in February 2014, she observed
tiny nodules, present bilaterally within the injection sites with
concomitant bluish discoloration of the adjacent skin. The
nodules were more numerous on the left hand side. The
patient presented for the follow up appointment only in
May 2015 reporting persistent lesions she was concerned
about. A thorough clinical examination was performed.
Next, the high frequency ultrasound (HFU) scan of the skin
was performed using Philips EPiQ 5 (Bothell, USA) scanner
equipped with L 18–5 broadband transducer and Derma View
scanner equipped with a 48 MHz mechanical transducer
(Dramiński, Poland). Subsequently, an incisional biopsy was
performed under a local anaesthesia with the approach from
the buccal mucosa on the left hand side, at the lip level. After
biopsy specimen collection, the incisional wound was closed
with absorbable sutures.
Formalin-fixed paraffin-embedded blocks were performed
containing altered tissue. Four micrometre sections were cut
from the blocks for routine H&E and immunohistochemical
analysis. The slides were incubated at 60ºC for 1 hour and
then allowed to cool. Deparaffinisation and antigen retrieval
were performed by subjecting the slides to Dako PT Link
(Dako, Denmark) with Envision FLEX Target Retrieval
Solution, High pH (Dako). The immunohistochemistry was
performed according to Envision FLEX kit (Dako) with appli-
cation of primary mouse CD68 antibody (Dako). The

CONTACT Mlosek Robert Krzysztof mpage@wp.pl Kondratowicza 8, 03-242 Warsaw, Poland

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 E. SKRZYPEK ET AL.
Figure 1. Clinical aspect about 2 years after injection of polycaprolactone-based
dermal filler (A, B); high frequency ultrasound of granuloma – Epiq 5 with
18 MHz probe (C); derma view with 48MHz probe (D), ST – subcutaneous tissue.
The margin between the epidermis and dermis is blurred, which indicates an
active inflammation in this area (C,D).
immunohistochemical stainings were carried out in Dako
Autostainer Link 68 (Dako) and performed according to the
manufacturer’s protocol.
Results
The nodules were firm, movable and not painful upon palpa-
tion. The HFU showed the hypoechogeneous lesion, with
irregular borders, sized 0.378 cm × 0.416 cm, located within
the subcutaneous tissue, approx. 0.5 mm below dermis
(Figure 1). Microbial studies showed numerous colonies of
Streptococus parasanguinis. Histopathology analysis showed
Figure 2. Photomicrography shows several round cystic spaces, distributed on a background of fibrous connective tissue, with mononuclear inflammatory infiltrate
and large foreign body giant cells engulfing polycaprolactone-based material (H&E). Inset: giant cell with asteroid body (H&E, original magnification × 400).
numerous round cavities within the giant cell cytoplasm or
adjacent to giant cells containing asteroid bodies. Numerous
giant cells were diffused on the matrix of fibrous connective
tissue accompanied by macrophage and lymphocyte infiltra-
tion (Figure 2). Immunohistochemistry analysis using the
anti-CD68 antibody confirmed the presence of numerous
macrophages and CD68-positive polynuclear giant cells
(Figure 3). The histopathological diagnosis was foreign body
granuloma. The patient was offered intralesional injections of
triamcinolone (1 mg/mL) and 5-fluorouracyl (5FU) (50 mg/
mL). The patient refused her consent to treatment. Having
withdrawn her consent, the patient did not attend any more
appointment and was, therefore, lost to follow up.
Discussion
Until now, the PCL-based dermal filler injections have been
assessed as highly effective, safe and offering high level of
patient satisfaction. The chemical structure of PCL-based
dermal filler offers a combination of smoothness, so impor-
tant for the filler, and appropriate microsphere size, which
prevents their phagocytosis. Thus, the filler stimulates natural
human skin response and natural healing processes by indu-
cing neocollagenesis (12,13). Neocollagenesis was confirmed
by Nicolau and Marijnissen-Hofsté (14), in a study in two
rabbits. Histopathology analysis performed 9 months follow-
ing the injection showed a complete resorption of Ellansé-S
and newly formed type I and III collagen fibres around the
Ellansé-M microspheres. Twenty months later, Ellansé-M
microspheres were still present and Picro-Sirius Red (PSR)
staining confirmed the presence of type I collagen mostly.
Neocollagenesis was also observed by Kim and Abel (10),
who in biopsy specimens collected 13 months following an
injection showed smooth, round microspheres sized
30–40 µm mainly within the dermis.

Figure 3. Immunohistochemistry reveals macrophages and CD68(+) multinu-
cleated giant cells.
The first research paper to report an efficacy study of PCL-
based dermal filler in a larger patient sample is the one by
Gritzalas (15), published in 2011. Based on obtained scores,
the author concluded that the filler was assessed as highly
effective by the patients, and hence it appeared “promising”.
The studies by Moers-Capri and Sherwood (8), conducted
in 2013 in a sample of 40 patients, showed patient satisfaction
rates of 90% and 75% after 12 and 24 months, respectively.
The studied products were considered safe and well tolerated.
The efficacy of PCL was also shown by Galadari et al. (6).
In their study, they compared PCL to non-animal stabilised
hyaluronic acid (NASHA) in a sample of 40 patients. The
obtained results suggest that the effect of PCL-based filler was
sustained over a longer period of time as compared to
NASHA, which resulted in a better patient satisfaction.
Also in 2013, another paper was published on the use of PCL-
based filler in hand rejuvenation (9). The study was performed in
five women, who had a score of 3–4 on the Hand Grading Scale
(HGS). All patients received a single injection of Ellansé-M onto
the dorsal surface of both hands. Patient satisfaction at 24 weeks
was 82% and probability of re-treatment using the same techni-
que was 88%. De Melo and Marijnissen-Hofsté conducted a
study involving an injection of PCL mixed with 2% lidocaine
directly before the procedure, in order to increase patient’s
comfort. They assessed the obtained results as beneficial for
both the physician and the patient (7).
As the discussed papers show, PCL-based dermal filler is
considered effective and highly valued by both patients and
physicians. It is generally recommended as well tolerated by
human tissues, safe and not associated with serious adverse
effects. The complications reported up to date typically devel-
oped shortly after the procedure and resolved spontaneously
within a short period of time. Gritzalas (15) reported oedema
in 12 of his 40 patients. The oedema persisted for about 2 days
and resolved spontaneously afterwards and bruises, which
occurred in 2 cases, resolved by Day 7. Moers-Capri and
Sherwood (8) reported oedema and bruises (in 34% and 5%
of cases, respectively), which resolved spontaneously. No late
complications manifesting as granulomas or nodules were
JOURNAL OF COSMETIC AND LASER THERAPY 3
observed. Galadari (6) observed mild adverse effects, which
resolved spontaneously, in 48% of his patients. The 24-week
follow up by Figueiredo (9) showed mild dorsal hand oedema
in two of five patients, with an onset within 24 hours follow-
ing an injection and a resolution within subsequent 24 hours,
after using non-steroid anti-inflammatory drugs (NSAIDs).
He did not report nodules, granulomas and other complica-
tions, either. It should be noted, though that marionette lines
and oral commissures are areas difficult to treat, due to the
absent structural support and the dynamics of major muscles
in the perioral area. Inexperienced clinician or improper
technique may contribute to long-term complications, just
as it is the case with any other dermal filler (16).
However, interpreting above findings it should be noted that
the discussed studies were conducted in relatively small patient
(or animal) samples. Furthermore, study subjects were divided
into subgroups who were injected different PCL-based filler
formulas, which additionally reduced subject count for a single
formula. Additionally, there are no studies to assess long-acting
PCL-based filler formulas. The methodology in the majority of
the discussed studies was based on visual assessment and such
assessment scales as Visual Analogue Scale (VAS), Wrinkle
Severity Rating Scale (WSSR), Global Aesthetic Improvement
State (GAIS) Hand and Grading Scale (HGS). Moreover, none
of this research (except for the studies of neocollagenesis con-
ducted in two rabbits and two human subjects) has included
objective assessment methods, such as histology or high fre-
quency ultrasonography. Therefore, their results should not be
seen as conclusive.
As our experience shows, PCL-based dermal fillers can also
cause a serious complication, manifesting as foreign body
granuloma. To the best of our knowledge, our case is the
first published report of granuloma secondary to polycapro-
lactone-based filler injection, confirmed both clinically, as well
as with ultrasound and histopathology studies.
Conclusions
Along with botulinum toxin, dermal fillers are the most com-
monly used substances in aesthetic medicine. Patients using
them are typically healthy individuals expecting improved
physical appearance as a result of the procedure.
Unfortunately, the ideal dermal filler is still yet to come. All
dermal fillers are associated with early, late or delayed adverse
effects. Our study shows it is true also for the PCL-based filler,
which seemed to be safe until recently. No severe adverse
events have been reported for 6 years since its launch.
Acknowledgments
The authors gratefully acknowledge the assistance of Karolina Kalisz in
translating and editing the manuscript.
Disclosure statement
The authors report no conflicts of interest.
4 E. SKRZYPEK ET AL.
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