|

Received: 18 September 2019    Accepted: 20 September 2019

DOI: 10.1111/jocd.13246

ORIGINAL CONTRIBUTION

Soft tissue distribution pattern of facial soft tissue fillers with

different viscoelastic properties

Gianna Rosamilia BS1 | Hassan Hamade BSc1 | David L. Freytag2 | Konstantin Frank MD2  |

Jeremy B. Green MD3 | Aditya Devineni MS1 | Diana L. Gavril MD4 |
Claudia A. Hernandez MD5 | Tatjana Pavicic MD6 | Sebastian Cotofana MD, PhD, PhD1,7

1
Division of Anatomy, Department of
Medical Education, Albany Medical College, Abstract
Albany, NY, USA Background: Soft tissue filler product distribution and tissue integration have been
2
Department for Hand, Plastic and Aesthetic
shown to depend on myriad factors including the injector type, injector size, and
Surgery, Ludwig–Maximilians University
Munich, Munich, Germany injection angle.
Aim: This study aims to investigate the magnitude of product spread across fascial
3
Skin Associates of South Florida, Coral
Gables, FL, USA
4
soft tissue layers in relation to product viscoelastic properties.
Private Practice, Cluj-Napoca, Romania
5 Patients/Methods: A total of 168 injection procedures were conducted in two fe-
Private Practice, Medellin, Colombia
6
Private Practice, Munich, Germany male Caucasian body donors with a mean age of 80 years (range: 79-81) and a mean
7
Division of Plastic Surgery, Department body mass index of 23.6 kg/m2 (range: 21.0-26.6). The injection procedures were per-
of Surgery, Albany Medical Center, Albany,
formed in the forehead, scalp, zygomatic arch, mandible, clavicle, and sternum. The
NY, USA
injected materials included Belotero® Soft, Belotero® Balance, Belotero® Intense,
Correspondence
Belotero® Volume, Radiesse®, and Radiesse® Plus. Layer-by-layer dissections were
Sebastian Cotofana, Division of Anatomy
and Surgery, Albany Medical College, 47 performed to investigate the vertical distribution of the injected product.
New Scotland Avenue MC-135, Albany, NY
Results: The mean product spread was for Belotero® Soft 4.54 ± 0.91; Belotero®
12208.
Email: cotofas@amc.edu Balance 3.85 ± 1.19; Belotero® Intense 3.04 ± 1.34; Belotero® Volume 2.58 ± 1.27;
Funding information Radiesse® 1.31 ± 0.47; and Radiesse® Plus 1.27 ± 0.45 with P < .001. Bivariate cor-
This study was supported by Merz North relations between product spread and storage modulus (G’) revealed an inverse rela-
America, Inc, Raleigh, NC, USA (Grant Nr:
05062019). tionship of moderate strength with rp = −0.651 and P < .001.
Conclusion: The results of the present study revealed that products that were more
fluid and less viscous distributed into more superficial fascial layers than products
that were less fluid and more viscous (P < .001). This relationship held true irrespec-
tive of injected location.

KEYWORDS

calcium hydroxylapatite, hyaluronic acid, rheologic properties, soft tissue fillers, viscoelastic
properties

1 |  I NTRO D U C TI O N Society of Plastic Surgeons, 2 676 907 soft tissue filler injections were
performed in 2018, a 3-fold increase compared to 2000.1 These fillers
The number of soft tissue filler injections performed in the United have gained popularity given that they are a nonsurgical option, come
States continues to rise. According to the annual report of the American at a relatively lower cost, and require little downtime. They have been

J Cosmet Dermatol. 2020;00:1–9. wileyonlinelibrary.com/journal/jocd© 2020 Wiley Periodicals, Inc.     1 |

 |
2       ROSAMILIA et al.
shown to provide long-term, natural-looking results for both correcting
2-14
facial aging and enhancing facial features. The range of products
used for injections has also greatly expanded. Of the injectable fillers,
hyaluronic acid and calcium hydroxylapatite are the two most widely
used, comprising 88% of soft tissue filler injections in 2018.1 These
fillers are characterized by different rheologic and physicochemical
profiles, which contribute to the esthetic outcome.
Understanding the unique rheological properties of each filler
can aid clinicians in selecting a particular product for a specific es-
thetic outcome or facial region. Since distinct regions of the face are
subjected to varying strains from skin tension, muscle activity, and
fat volume, fillers will deform in ways depending on where and how
they are injected.15 There is not one product appropriate for every
indication; thus, recognizing how rheologic and physicochemical
properties influence esthetic outcomes is incredibly valuable.15,16
This knowledge would aid clinicians in assessing the anatomical
placement of a specific product and the appropriate depth of implan-
15
tation. However, the rheology of fillers is complex, and laboratory
measurements may not translate to clinical observations.
Recent studies have shown that once injected into the facial soft
tissues, filler materials distribute with high variability depending on
14
whether they were injected with a needle or a cannula, the size of
the needle or cannula17 and the injection angle utilized.17 In these ex-
perimental cadaveric studies, co-influencing factors (facial region and
product characteristics) were kept constant, and the injected material
migrated into neighboring fascial layers. The greatest potential for
uncontrolled product spread was found to be associated with needle
injections (versus cannula), the use of a 25-G needle and an injection
angle of 90 degrees. This uncontrolled product spread poses a risk for
13
adverse vascular events. The injected product may reach more vas-
cularized fascial layers (ie, the subdermal plane) and can thereby enter
the arterial vascular system if a through-and-through phenomenon
occurred during needle insertion. Additionally, uncontrolled product
spread can result in surface irregularities and product visibility if the
product migrated superficially into the subdermal plane. This can be
esthetically unappealing especially in the tear trough or the forehead.
However, uncontrolled product spread can also depend on the vis-
coelastic properties of the injected filler material itself. It can be hy-
pothesized that a more viscous product (less fluid and more viscous)
migrates less as compared to a less viscous product (more fluid and less
viscous) which migrates more. To test this hypothesis, we conducted
the present experimental cadaveric study where we objectively ana-
lyzed the magnitude of product spread across fascial soft tissue layers
depending on the viscoelastic properties of an injected filler material
utilizing a 27G 13-mm needle at 90-degree injection angle.
2 |  M ATE R I A L S A N D M E TH O DS
2.1 | Study sample
A total of 168 injection procedures were conducted in two female
Caucasian body donors with a mean age of 80 years (range: 79-81)
and a mean body mass index of 23.6  kg/m2 (range: 21.0-26.6) ob-
tained from and dissected at Albany Medical College, Albany, NY,
USA. The specimens were screened and not included in the analysis
if previous surgery, trauma, or diseases disrupted the integrity of the
anatomy of the face and body. Each body donor gave informed con-
sent while alive for the use of their body for medical, scientific, or
educational purposes. All elements of the study conformed to the
laws of the country where the study was conducted (USA).
2.2 | Injection procedure
A total of 156 injection procedures were performed in the forehead,
scalp, zygomatic arch, mandible, clavicle, and sternum. All injection
procedures were conducted using a 27G 13-mm sharp-tip needle
(TSK Laboratory) at a 90-degree injection angle, perpendicular to
the bone surface. The bone surface was identified via palpation, and
bony contours were followed during the injection procedures.
The injected materials included Belotero® Soft, Belotero®
Balance, Belotero® Intense, Belotero® Volume, Radiesse®, and
Radiesse® Plus (Merz Pharma). The Belotero® products were stained
with 0.05 cc of 0.1% toluidine blue solution prior to injection for bet-
ter visibility during the dissection process. The Radiesse® products
were left unstained as the products were white in color. Information
on the storage modulus (G’) of the stained and unstained products
are given in Table 1.
A total of 0.2 cc was injected per injection procedure, and a se-
ries of 6 injection procedures (each tested product) was performed
in the same location. Injections were performed by the same person
(GR), who had trained with syringe force testing to ensure constant
pressure on the plunger during injections, in order to maintain con-
sistency between injection procedures.
TA B L E 1   Storage modulus (G’) in Pascal (Pa) of the products
used in the study, as determined by laboratory testing. (Data
provided by Merz Pharma GmbH & Co. KGaA, Frankfurt/Main,
Germany)
Storage
modulus (G’)
Merz filler injection product (Pa)
Belotero® Soft without toluidine blue 9.26 ± 0.10
Belotero® Soft with 0.05 mL 1% toluidine blue 6.99 ± 0.32
®
Belotero Balance without toluidine blue 49.4 ± 3.00
Belotero® Balance with 0.05 mL 1% toluidine 39.2 ± 3.05
blue
Belotero® Intense without toluidine blue 145.2 ± 1.96
Belotero® Intense with 0.05 mL 1% toluidine 119.2 ± 2.07
blue
Belotero® Volume without toluidine blue 232.7 ± 5.00
®
Belotero Volume with 0.05 mL 1% toluidine 208.8 ± 2.45
blue
Radiesse® without toluidine blue 1584.1 ± 67.47
Radiesse® Plus without toluidine blue 817.6 ± 57.30
ROSAMILIA et al.
2.3 | Anatomical dissection
Cross-sectional dissections were performed to verify the vertical
distribution of the injected product. Dissections were facilitated by
the added blue dye to the injected material (Belotero® range only).
In particular, the layered arrangement of the injected areas were
identified as follows: Layer 1: skin, Layer 2: superficial fatty layer,
Layer 3: superficial fascia (contiguous structures: frontalis muscle/
superficial musculo-aponeurotic system (SMAS)/galea aponeurot-
ica), Layer 4: deep subcutaneous fatty layer/loose areolar layer, and
Layer 5: periosteum/muscle. Layers 2 and 4 were additionally sub-
divided into a superficial segment, termed 2minus or 4minus, and
a deep segment, termed 2plus or 4plus (Figure 1). The additional
term “minus” was added to identify whether the product was lo-
cated more superficially and thus closer to the next adjacent more
superficial layer, that is, skin (Layer 1) or to the superficial fascia
(Layer 3) whereas the term “plus” was added to identify whether
the product was located deeper and thus closer to the next adjacent
deeper layer, that is, superficial fascia (Layer 3) or to the periosteum
(Layer 5).
2.4 | Ultrasound imaging
Ultrasound imaging of each injected region was performed
after the injection procedure but before cadaveric dissections
using a linear 15  MHz transducer (MTurbo portable, Fujifilm
SonoSite, Inc) to provide noninvasive visual confirmation of
Product in:
Layer 2minus
Product in:
Layer 2plus
Product in:
Layer 4minus
Product in:
Layer 4plus
Mean Product Spread: 4.54 3.85 3.04
F I G U R E 1   This figure shows a schematic drawing of the skin and the mean product spread within the layers of the skin for each
product used in the study. The layers of skin are as follows: Skin: Layer 1, Superficial fatty layer: Layer 2, Superficial fascia: Layer 3, Loose
areolar tissue (or Deep fatty layer where present): Layer 4, Periosteum (or Deep Fascia where present): Layer 5. The different colors are
representing the different types of product (yellow = Belotero Soft; orange = Belotero Balance; red = Belotero Intense; violet = Belotero
Volume; Blue (1) = Radiesse; Blue (2) = Radiesse Plus)
      3|
product migration and integration. Due to the decreased resolu-
tion of the imaging methodology only pictorial (and not statisti-
cal) analyses of the tissue integration process upon massage was
performed.
2.5 | Tissue-product integration
Two injection series (n  =  12) were performed in the medial thighs
bilaterally; one without tissue massage and one with tissue massage.
Injections were performed here with the complete insertion of the
13-mm needle into the subcutaneous fat. A massage was performed
with even, firm pressure over a period of three minutes on one side.
Ultrasound images and anatomical dissections were conducted to
compare tissue-product integration between the massage and the
nonmassage region. This injection series was not used for statistical
analyses.
2.6 | Statistical analyses
Upon dissection, layered distribution of the colored product was
recorded and related to each type of product injected. Product dis-
tribution was assessed by the count of layers the product migrated
retrograde through along the created injection canal. The most su-
perficial tissue layer of product spread was documented, and the
number of layers the product traversed (distribution) was calculated
for analysis, that is, if a product spread to layer 2plus, it distributed
Dermis
Superficial fatty layer
Superficial fascia
Loose areolar tissue
Periosteum
2.58 1.31 1.27
 |
4       ROSAMILIA et al.
across 4 layers (4plus, 4minus, 3, 2plus). A one-way ANOVA analysis
with Tukey post hoc testing, bivariate correlations, and logistic re-
gression analysis was run to assess the relationship between product
distribution and rheological properties, specifically storage modu-
lus (G’) of each injected product type using SPSS Statistics 23 (IBM).
Results were considered statistically significant at a probability level
of ≤.05 to guide conclusions.
3 |   R E S U LT S
3.1 | General description
A total of 168 injection procedures were performed utilizing a 27G
13-mm needle at an injection angle of 90 degrees with the sharp
needle tip being in constant contact with bone during product ap-
plication. Twenty four injection procedures were performed each
in the forehead, zygomatic arch, mandible, clavicle, and sternum,
and 36 in the scalp. Twelve additional injections were performed
in the medial thigh, which were not included in the statistical anal-
yses. In each of the injection locations, a series consisting of six
®
individual injections was performed. Those included: Belotero
® ® ®
Soft, Belotero Balance, Belotero Intense, Belotero Volume,
Radiesse®, and Radiesse® Plus. This resulted in 28 injections per-
formed per product.
Laboratory product testing revealed a decrease in storage modu-
lus (G’) after the toluidine blue was added with P = 0.07. Despite not
reaching statistical significance, it was revelaed that the dye changed
the viscoelastic properties of the product by making the dyed prod-
uct more fluid than the undyed product. In the present study dyed
® ®
Belotero and undyed Radiesse products were used (Table 1).
F I G U R E 2   This figure shows bar
graphs, representing the mean product
spread of all the products used in the
study and their corresponding layer
of the skin, in which they distributed
after injection. The different colors
are representing the different types
of product (yellow = Belotero Soft;
orange = Belotero Balance; red = Belotero
Intense; violet = Belotero Volume; Blue
(1) = Radiesse; Blue (2) = Radiesse Plus)
3.2 | Cadaveric dissections
Upon visual inspection during the dissection procedure, the prod-
uct distribution was observed to resemble the shape of a colored
mound extending from the supraperiosteal plane reaching into more
superficial layers. The mean product spread (measured in layers)
independent of region was for Belotero® Soft 4.54  ±  0.91 (range:
2-5); Belotero® Balance 3.85 ± 1.19 (range: 2-5); Belotero® Intense
3.04 ± 1.34 (range: 1-5); Belotero® Volume 2.58 ± 1.27 (range: 1-5);
Radiesse® 1.31 ± 0.47 (range: 1-2); Radiesse® Plus 1.27 ± 0.45 (range:
1-2) with P < .001 across product type (Figures 1 & 2). This indicates a
statistically significant difference in mean product spread = product
behavior between the investigated product types, with Belotero®
Soft having the greatest product spread (Figure 2).
3.3 | Difference between injected locations
For each individual Belotero® product, it was observed that there was
no statistically significant difference in mean layered product spread
across injected regions: Belotero® Soft with P  =  .693 and a maxi-
mum distribution in the chest and clavicle with 5.0 ± 0.00; Belotero®
Balance with P = .858 and a maximum distribution in the scalp with
4.33 ± 1.21; Belotero® Intense with P = .264 and a maximum distribu-
tion in the scalp with 4.0 ± 1.10; Belotero® Volume with P = .139 and
a maximum distribution in the scalp with 3.83 ± 1.47 (Figure 3).
The Radiesse® product line distributed maximally in two layers
(4minus and 4plus) but reached statistical significance across regions
with P = .028. The maximum distribution was observed in the scalp
with 1.83 ± 0.41 layers. A similar trend was observed for Radiesse®
Plus with the greatest distribution in the scalp with P = .005.
ROSAMILIA et al. |
      5

F I G U R E 3   This figure shows bar

graphs, representing the mean product
spread of all the products used in the
study and their corresponding layer
of skin, in which they distributed
after injection in the different
treated areas. The colors represent
the different areas, where the
product was injected (blue = scalp;
green = forehead; brown = zygomatic
arch; violet = mandible; yellow = chest;
red = clavicle)

F I G U R E 4   This figure shows the (A) (B)

location of the dyed product (Belotero
Soft) after cadaveric dissection (A).
Picture B shows the ultrasonic picture of
the respective treated area. The green
dots circle the injected product, which is
labeled with the letter A

rp = −0.651 and P < .001 indicating that a product with a higher G’

3.4 | Difference between individual products
® ®
Using Belotero Soft as a reference, Belotero Balance did not
distribute statistically significantly different (independent of re-
gion) with a mean difference in product spread of 0.692 layers and
P = .136. All other products distributed statistically significantly less
with P  <  .001. The mean differences in product spread (compared
to Belotero® Soft) are as follows: Belotero® Intense, 1.50 layers;
Belotero® Volume, 1.96 layers; Radiesse®, 3.23 layers; Radiesse®
Plus, 3.27 layers.
3.5 | Correlation between viscoelastic
properties and tissue distribution
Calculating bivariate correlations between product spread and
the storage modulus (G’) (obtained from the dyed products; see
Table 1) revealed an inverse relationship of moderate strength with
distributes significantly less into other layers.
Univariate linear regression models revealed that 42.3% of the
variation in product spread could be explained by the storage modu-
lus (G’) with R 2 = 0.420. The regression model statistically significantly
predicted the product spread with P < .001. The respective regres-
sion equation to estimate layered product spread based on the G' of a
product is as follows: Layered product spread = 3.587 − (0.002 × G’).
Utilizing the product distribution equation above, a product with
a G’ of 1293.5 can result in an estimated maximum product spread of
one layer, a product with a G’ of 793.5 can result in an estimated max-
imum product spread of two layers, and a product with a G’ of 293.5
can result in an estimated maximum product spread of three layers.
3.6 | Tissue-product-integration upon massage
Upon mechanical compression via tissue massage, it was observed
that Belotero® Soft integrated most into the surrounding soft
 |
6       ROSAMILIA et al.
(A) (B)
(A) (B)
tissue. The products that integrated the least were Radiesse® and
®
Radiesse Plus. Pictorial description is provided in Figures 4-10.
4 |  D I S CU S S I O N
This experimental cadaveric study was designed to investigate the
influence of viscoelastic properties of selected soft tissue fillers on
product distribution and product tissue integration. A total of 168
injection procedures were performed in various facial and trunk
regions (forehead, scalp, zygomatic arch, mandibular angle, clavi-
cle, and sternum), utilizing the following products: Belotero ® Soft,
Belotero® Balance, Belotero® Intense, Belotero® Volume (stained
® ®
with toluidine blue), Radiesse , and Radiesse Plus (unstained). All
injection procedures were conducted using a 27G 13-mm needle
at a 90-degree injection angle, perpendicular to the bone surface,
in the same location and performed by the same person to ensure
consistency. The results of the present study revealed, although
all injections were of 0.2 cc with the tip of the needle in constant
contact with bone, products that were more fluid and less viscous
distributed to a statistically significantly greater magnitude into
more superficial fascial layers than products that were less fluid
and more viscous with P < .001. This relationship held true regard-
less of injected location. Using the tested storage modulus (G’) of
the selected soft tissue fillers, we were able to compute a formula
by which the product spread could be estimated depending on the
given G’: Product distribution = 3.587 − (0.002 × G’). This formula
can be applied to any soft tissue filler not only to those tested
herein.
F I G U R E 5   This figure shows the
location of the dyed product (Belotero
Balance) after cadaveric dissection (A).
Picture B shows the ultrasonic picture of
the respective treated area. The green
dots circle the injected product, which is
labeled with the letter A
F I G U R E 6   This figure shows the
location of the dyed product (Belotero
Intense) after cadaveric dissection (A).
Picture B shows the ultrasonic picture of
the respective treated area. The green
dots circle the injected product, which is
labeled with the letter A
One strength of the study is the number of injection procedures
performed (n  =  168). A large number of observations increase the
validity of obtained results as it stabilizes values to the mean and can
thus reduce the effects of confounding factors. Another strength of
this study is that we kept constant the needle size (27G 13 mm) and
injection angle (90 degrees). This needle size is commonly used to in-
ject soft tissue fillers and this angle of approach is often employed in
the live clinical setting; thus, potentially rendering the results extrap-
olatable to esthetic practice. A third strength involves the anatomic
dissections performed immediately after the injection procedure to
accurately analyze product distribution, whether it had been dis-
placed along the needle track to more superficial fascial layers, or in
which specific segment of Layer 4 (deep subcutaneous fatty layer/
loose areolar layer) the product was located. Noninvasive imaging
like ultrasound, computerized tomography, or magnetic resonance
imaging has less spatial resolution for the detection of product,
thereby potentially reducing the accuracy in detecting the proper
product location in relation to fascial layers. The injected product
might integrate into the soft tissues and even if contrast-enhanced
substances were used, 0.2 cc would be difficult to detect via imaging
in relation to the soft tissue layers.
A limitation of the study, which inherent in any cadaveric study,
is that the investigated subjects are not alive. Thus, they lack blood
pressure, basic muscle tone, regular tissue turgor pressure and have
a different body temperature when compared to living individuals.
The aim of the present study was to identify the product distribution
of the dyed injected material into various facial and trunk regions.
The layers of these regions are not expected to change with aging
or postmortem. Thus, the layered position of the injected product
ROSAMILIA et al. |
      7

F I G U R E 7   This figure shows the (A) (B)

location of the dyed product (Belotero
Volume) after cadaveric dissection (A).
Picture B shows the ultrasonic picture of
the respective treated area. The green
dots circle the injected product, which is
labeled with the letter A

F I G U R E 8   This figure shows the (A) (B)

location of the dyed product (Radiesse)
after cadaveric dissection (A). Picture
B shows the ultrasonic picture of the
respective treated area. The green dots
circle the injected product, which is
labeled with the letter A

F I G U R E 9   This figure shows the (A) (B)

location of the dyed product (Radiesse
Plus) after cadaveric dissection (A).
Picture B shows the ultrasonic picture of
the respective treated area. The green
dots circle the injected product, which is
labeled with the letter A

should be identical when compared to the same individual at a
younger age or while alive. Still, using a cadaveric model allows one
to conduct a series of injections (6 injections per region and side)
according to a standardized injection protocol which would not be
ethically possible in a living patient. Another limitation of this study
is that products from only one company (Merz Pharma) were inves-
tigated. This could create a bias in the interpretation of the results.
To account for this, we used the laboratory tested storage modulus
(G’) of the injected materials to compute a formula which is based on
any given G’. The applied linear regression model statistically signifi-
cantly predicted the product spread with P < .001. This formula can
be used to estimate product spread based on the (brand-indepen-
dent) storage modulus. It can provide information on the number of
fascial layers an injected product will spread across.
The generated formula revealed that with a 27G needle and a
90-degree injection angle, injected product of lower than 293.5
(Pa) will result in uncontrolled product spread of more than 3 fascial
layers independent of injection location. This is of great clinical rele-
vance when injecting soft tissue fillers. Besides injector type (needle
vs. cannula),14 needle size, and injection angle,17 the results of the
present study reveal that also the G’ of the injected product plays
a critical role in soft tissue product distribution. A statistically sig-
nificant inverse relationship exists between storage modulus G’ and
product spread with rp = −0.651 and P < .001. This indicates that a
more fluid and less viscous product has significantly increased po-
tential to spread uncontrolled into superficial layers even if the sharp
needle tip is in constant contact with the bone during the application
process. In contrast, a less fluid and more viscous product will spread
significantly less across fascial planes and remains in the fascial layer
where the sharp needle tip was initially introduced.
For daily clinical use, the results of the present study indicate
that a product's G’ should be considered when planning injection
technique/targeted anatomic layer. If the supraperiosteal plane with
the deep facial fat compartments18 is targeted, the G’ of the product
 |
8       ROSAMILIA et al.
R L
should be at least 1293.5 Pa (disregarding other product viscoelastic
parameters) if 100% of the injected product is supposed to remain in
the supraperiosteal plane. A product of lesser G’ will result in migra-
tion into more superficial layers; this uncontrolled product spread will
position some of the product into the deep subcutaneous (subdermal)
fat and will result in a reduced amount of product remaining in the
targeted layer, here the supraperiosteal plane. A reduced amount of
product in the intended layer of injection indicates less precise prod-
uct injection but also a reduced volumizing and thus esthetic effect.
This indicates that the correct product choice will influence the es-
thetic outcome and has to be incorporated into the therapeutic plan.
If the goal is to volumize deep facial fat compartments, a more
fluid and less viscous product is a poor choice for supraperiosteal
injections. The results of the present study reveal that this type of
product will spread across fascial layers and will position product
in all fascial planes including subdermally. This is of greatest inter-
est for facial regions where soft tissue thickness is reduced like the
forehead or the tear trough. Here, the injection of a soft product
should be avoided if the layer of intended product placement is the
supraperiosteal plane. A softer product will partially spread super-
ficially into the subdermal plane. There the product could lead to
surface irregularities and product visibility. In the tear trough, this is
of even greater importance as the lymphatic outflow is connected to
the orbicularis oculi muscle which is located in the subdermal plane.
Supraperiosteal positioned softer product will leave that plane and
distribute subdermally where it can be visible (Tyndall effect) and
lead to surface irregularities. Also, the product will integrate into the
muscle where the product might block lymphatic outflow and can
cause swelling and edema locally.
An additional series of injections was performed bilaterally in
the subcutaneous fat of the medial thigh. Before the region was
dissected, manual massaging for 3  minutes was performed to me-
chanically induce tissue integration of the product. The dissection
F I G U R E 1 0   This figure shows two
pictures of a cadaveric dissection of
the medial thigh. Picture R shows the
distribution of the dyed product in the
right medial thigh, with no massage
applied after injection. Picture L shows
the distribution of the dyed product
in the left medial thigh of the same
body donor, with massage applied after
injection. The colored arrows indicate
the different product types used during
the study (yellow = Belotero Soft;
orange = Belotero Balance; red = Belotero
Intense; violet = Belotero Volume; Blue
(1) = Radiesse; Blue (2) = Radiesse Plus)
results revealed that a softer product integrated better into the tis-
sue as compared to a more viscous product. This is confirmatory and
plausible at a same time as a soft product can be better integrated
and massaged into the tissue due to its low stability. Clinically, this
can be utilized to integrate and mold softer products better into the
surrounding soft tissues potentially resulting in a more homogenous
esthetic outcome. This characteristic may also guide adverse events
management. Based on the results of the present study it can be
confirmed that a more viscous product can be appreciated (poten-
tially by palpation or ultrasound) easier than a softer product. A less
viscous product might be potentially more difficult to identify due to
its tissue integration whereas a more viscous product can be better
identified and ultimately targeted.
5 | CO N C LU S I O N
The results of the present study revealed, although all injections
were of 0.2  cc with the tip of the needle in constant contact with
bone, products that were more fluid and less viscous distributed to
a statistically significantly greater magnitude into more superficial
fascial layers than products that were less fluid and more viscous
with P < .001. This relationship held true regardless of injected loca-
tion. Using the tested storage modulus (G’) of the selected soft tis-
sue fillers, we were able to compute a formula by which the product
spread could be estimated depending on the given G’: Product dis-
tribution = 3.587 − (0.002 × G’). This formula can be applied to any
soft tissue filler not only to those tested herein.
C O N FL I C T O F I N T E R E S T
None of the other authors listed have any commercial associations
or financial disclosures that might pose or create a conflict of inter-
est with the methods applied or the results presented in this article.
ROSAMILIA et al.
ORCID
Konstantin Frank  https://orcid.org/0000-0001-6994-8877
REFERENCES
1. American Society of Plastic Surgeons. 2018 National Plastic
Surgery Statistics. 2018. https​://www.plast​icsur​gery.org/docum​
ents/News/Stati​stics/​2018/plast​ic-surge​r y-stati​stics-report-2018.
pdf. Published 2019. Accessed April 14, 2019.
2. Cotofana S, Schenck TL, Trevidic P, et al. Midface: clinical anatomy
and regional approaches with injectable fillers. Plast Reconstr Surg.
2015;136:219S-234S.
3. Cotofana S, Koban CK, Frank K, et al. The surface-volume-coefficient
of the superficial and deep facial fat compartments – a cadaveric
3D volumetric analysis. Plast Reconstr Surg. 2019;143(6):1605-1613.
4. Cotofana S, Gotkin RH, Frank K, et al. The functional anatomy of
the deep facial fat compartments – a detailed imaging based inves-
tigation. Plast Reconstr Surg. 2019;143(1):53-63.
5. Schenck TL, Koban KC, Schlattau A, et al. Updated anatomy of the
buccal space and its implications for plastic, reconstructive and aes-
thetic procedures. J Plast Reconstr Aesthetic Surg. 2018;71(2):162-170.
6. Suwanchinda A, Webb KL, Rudolph C, et al. The posterior temporal
supraSMAS minimally invasive lifting technique using soft-tissue
fillers. J Cosmet Dermatol. 2018;17(4):617-624.
7. Suwanchinda A, Rudolph C, Hladik C, et al. The layered anatomy of
the jawline. J Cosmet Dermatol. 2018;17(4):625-631.
8. Matarasso SL, Carruthers JD, Jewell ML. Restylane Consensus
Group. Consensus Recommendations for Soft-Tissue Augmentation
with Nonanimal Stabilized Hyaluronic Acid (Restylane). Plast
Reconstr Surg. 2006;117:3S-34S.
9. Scheuer JF, Sieber DA, Pezeshk RA, Gassman AA, Campbell CF,
Rohrich RJ. Facial danger zones: techniques to maximize safety during
soft-tissue filler injections. Plast Reconstr Surg. 2017;139(5):1103-1108.
10. Pavicic T, Yankova M, Schenck TL, et al. Subperiosteal injections
during facial soft tissue filler injections-Is it possible? J Cosmet
|
      9
Dermatol. 2019. https​://doi.org/10.1111/jocd.13073​ [Epub ahead
of print].
11. Pavicic T, Frank K, Erlbacher K, et al. Precision in dermal filling: a
comparison between needle and cannula when using soft tissue
fillers. J Drugs Dermatol. 2017;16(9):866-872.
12. Fabi S, Pavicic T, Braz A, Green J, Seo K, van Loghem J. Combined
aesthetic interventions for prevention of facial ageing, and res-
toration and beautification of face and body. Clin Cosmet Investig
Dermatol. 2017;10:423-429.
13. Pavicic T, Mohmand HM, Yankova M, et al. Influence of needle size
and injection angle on the distribution pattern of facial soft tissue
fillers. J Cosmet Dermatol. 2019;18(5):1230-1236.
14. Rohrich RJ, Ghavami A, Crosby MA. The role of hyaluronic acid
fillers (Restylane) in facial cosmetic surgery: review and technical
considerations. Plast Reconstr Surg. 2007;120(6 suppl):41S-54S.
15. Fagien S, Bertucci V, von Grote E, Mashburn JH. Rheologic and
physicochemical properties used to differentiate injectable hy-
aluronic acid filler products. Plast Reconstr Surg. 2019;143(4):
707e-720e.
16. Pierre S, Liew S, Bernardin A. Basics of dermal filler rheology.
Dermatol Surg. 2015;41:S120-S126.
17. Pavicic T, Webb KL, Frank K, Gotkin RH, Tamura B, Cotofana S.
Arterial wall penetration forces in needles versus cannulas. Plast
Reconstr Surg. 2019;143(3):504e-512e.
18. Cotofana S, Gotkin RH, Frank K, et al. The functional anat-
omy of the deep facial fat compartments. Plast Reconstr Surg.
2019;143(1):53-63.
How to cite this article: Rosamilia G, Hamade H, Freytag DL,
et al. Soft tissue distribution pattern of facial soft tissue
fillers with different viscoelastic properties. J Cosmet
Dermatol. 2020;00:1–9. https​://doi.org/10.1111/jocd.13246​