SEPTEMBER 2011
`
`COPYRIGHT © 2011
`
`OIUCIN:\L ARTICLES
`SPECIAL TOPIC
`
`VOLUME 10 • ISSUE 9
`
`joURNAL OF DRUGS IN DERMATOLOGY
`
`Rheological Evaluation of the Physical Properties
`of Hyaluronic Acid Dermal Fillers
`
`David Stocks,• Hema Sundaram MD,b Jason Michaels MD,c Manzer J. Durrani PhD,
`Mitchell S. Wortzman PhD, Diane B. Nelson BSN MPHd
`•[ntertek MSG, Redcar, United Kingdom
`IISundaram Dermatology, Cosmetic & Laser Surgery Center, Rockville, MD and Fairfax, V .A
`< .Aspire Cosmetic Med Center, Las Vegas, NV
`4Medicis Aesthetics Corporation, Scottsdale, AZ
`
`-
`
`-
`
`· \ B ~ I R :\ C I
`
`1
`
`- - - -
`
`Background: Hyaluronic acid (HA) gels are commonly 1niected into the skin to lift rhytides and to improve facial appearance. The differ(cid:173)
`ent processes used in their manufacture and formulatlon yield products with unique physical characteristics that play an important role in
`predicting their clinical performance.
`Objective: The following rheologic evaluatlon was performed to objectively measure the physical characteristics of HA dermal filler prod(cid:173)
`ucts derived from similar bacterial sources and containing the same butanediol diglycidyl ether cross-linker. but formulated using different
`manufacturing techniques. The objective of this study was to evaluate the physical characteristlcs of two distinct femmes of HA products,
`thereby providing clinicians with a greater understanding of these products' attributes and the ability to optimize their use in the treatment
`of patients seeking facial rejuvenation.
`Maartals and M.thods: The physical properties of commercially-available dermal fillers containing HA were evaluated using rheologic
`testing methods under clinically-f'elevant conditions. Additionally, light microscopy was used to assess the particulate nature of each prod(cid:173)
`uct.
`ANll!ts: The gels tested demonstrated a broad range of elasticity, firmness and viscosity. Light microscopy confirmed the particulate
`nature of each product and revealed HA particles of varying size and distribution.
`Conclusion: This rheologic evaluation demonstrates that differences exist among the HA products tested including gel elasticity, viscos(cid:173)
`ity, and the range and distribution of gel particle sizes. Understanding the distinct physical characteristics of different HA dermal fillers
`and how these characteristics may predict their clinical behavior can assist clinicians in achieving the desired results in patients seeking
`facial rejuvenation.
`
`J Drugs Dermatol. 2011;10(9):974-980.
`
`I NTR<) I lUCTI ON
`
`H yaluronic acid (HAI is a glycosaminoglycan that con(cid:173)
`
`sists of repeating units of glucuronic acid and N(cid:173)
`acetyl-glucosamine (hyaluronan) and which readily
`dissolves in water to form a viscous gal. It is found in the extra(cid:173)
`cellular matrix of many tissues, and approximately one-half of
`the HA in the human body is found in the skin where it plays an
`important role in providing structure and maintaining normal
`moisture content. 1 During the aging process, the HA content of
`the dermis decreases and this contributes to volume loss, di+
`minished dermal water-binding capacity and the development
`of rhytides.2 As HA is a physiologic component of human skin,
`HA-containing products are well-suited for use as dermal fillers
`in treating patients seeking facial rejuvenation.
`
`Commercially-available HA dermal fillers are similar in many re(cid:173)
`spects. They all contain HA obtained through the fermentation
`of Streptococcus sp. bacteria and the HA molecules are joined
`together using cross-linkers such as butanediol diglycidyl ether
`IBDDEI to prevent rapid in vivo enzymatic and oxidative deg(cid:173)
`radation.1.2 Despite these similarities, HA dermal fillers differ in
`their physical characteristics and therefore may behave clini(cid:173)
`cally in different ways, based upon the manufacturing methods
`used,U which determine the type and extent of HA cross-linking
`and the size and concentration of HA particles.1.3
`
`For example, five HA dermal fillers contain HA derived from
`similar bacterial cultures and are stabilized with the same BODE
`
`ALL 2061
`PROLLENIUM V. ALLERGAN
`IPR2019-01505 et al.
`
`

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`JOURNAL OF DRUGS IN DERMATOLOGY
`SEPTEMBER 2011 • VOLUME to • ISSUE 9
`
`975
`D. Stocks, H . Sundaram, J. Michaels, et al.
`
`cross-linker. One family of products contains HA that is manufac(cid:173)
`tured using a patented NASHA™ process while another utilizes
`a proprietary Hylacross™ technology.2 Regardless of the manu(cid:173)
`facturing methods employed, each produces gels containing
`particulate HA u Differences include particle size distribution,'"
`total HA concentration ,,3 and the extent of crosslinking. ,.u, Fully
`hydrated gels that have reached their maximum water-binding
`capacity will not swell following injection while there is a tenden(cid:173)
`cy for less hydrated gels to swell after injection.' Together, these
`properties may alter the firmness, elasticity and viscosity of the
`gels and impact the way they behave in the skin, including the
`amount of structural support or lift they provide which is related
`to the extent to which they improve the appearance of rhytides.
`
`Rheology is a branch of physics that studies how materials such
`as HA gels behave in response to applied forces. The physical
`properties of HA gels are described using a variety of rheologic
`terms (Table 1). One of the most frequently discussed charac(cid:173)
`teristics of HA gels is the elastic modulus, represented by the
`symbol G' (G prime I. This is the ability of a gel to resist deforma(cid:173)
`tion by an applied force. A gel with a numerically higher value
`for G' is better able to resist alterations in shape and is described
`as being firmer, harder or more elastic than a gel with a lower
`G'. As gels with a higher G' store a greater amount of the en(cid:173)
`ergy being applied to them, this property may also be referred
`to as the storage modulus. More stored energy allows a gel to
`TABLE 1.
`
`Rheology Terms Used t o Describe Hyaluronic Acid Gels
`
`Elasticity
`
`Elastic modulus
`
`I
`
`Viscosity
`
`Viscous modulus
`
`Complex modulus
`
`Complex viscosity
`
`Sheer force
`
`Shear thinning
`
`The ability ofa gel to •spring back• to
`its original shape after being deformed.
`A measure of stored energy in a
`viscoelastic material, represented by
`the 1ymbol G'.
`
`The flow characteristics of a gel; used
`to define gel thickness.
`
`A measure of dissipated energy in a
`viscoelastic material rapreaanted by
`the symbol G".
`
`The total resistance to deformation of a
`HA gel determined by the vector sum of
`G' and G". represented by the symbol G•.
`
`The viscosity calculated from
`frequency sweep, represented by 11•,
`the Greek letter eta.
`A term used to describe HA gels which
`poss8S8 both elastic and viscous
`properties.
`
`An external force which ia applied
`parallel to a gel by placing it between two
`platea that twist in opposite directions
`Decreasing gel viscosity with
`increasing rate of deformation.
`
`"spring back" to its original shape to a greater extent after being
`deformed. Clinically, dermal fillers with higher G' values are ex(cid:173)
`pected to provide greater structural support and volumization.2
`
`Understanding the distinct physical
`characteristics of different HA dermal
`fillers and how these characteristics may
`predict their clinical behavior can assist
`clinicians in achieving the desired results
`in patients seeking facial rejuvenation.
`
`Another important property of HA gels is viscous modulus, repre(cid:173)
`sented by the symbol G" (G double prime). Gels with numerically
`higher values of G • are described as being thicker or more viscous
`than gels with a lower G". Since a greater amount of energy a~
`plied to gels with a higher G" is lost as dissipated heat. G" is also
`refarred to as loss modulus. A related property is complex viscos(cid:173)
`ity, represented by the symbol 11• (Greek letter etal. This is the
`ability of the gel structure to resist shear forces. A shear force may
`be applied to a gel by placing it between parallel plates rotating in
`opposite directions. If the shear rate is steadily increased, the gel
`will reach a critical point where 11• will gradually decrease. This
`phenomenon is known as shear thinning. Although the physical
`properties of HA dermal fillers are often reported in terms of G'
`and G•,•.s a more comprehensive measure of the total resistance
`to deformation is known as the complex modulus which is the
`sum of G' and G" and is represented by the symbol G*.1
`
`Previous rheologic studies have evaluated the physical proper(cid:173)
`ties of a variety of commercially-available HA-containing fillers,
`demonstrating that these products possess a range of elastic1.u
`and viscous characteristics.B.11 Understanding these differences is
`relevant to the practicing clinician as it impacts filler product selec(cid:173)
`tion and injection location, based on the needs and desired results
`of the patienL Numerous clinical studies have established the ef(cid:173)
`fective use of HA dermal fillers for soft-tissue augmentation•o-11
`;
`however, understanding of the differences in the physical charac(cid:173)
`teristics of these products may enable clinicians to better predict
`their clinical performance and thus to optimize patient outcomes.
`
`The following rheologic study was performed to better un•
`derstand the physical properties of two widely used families
`of HA dermal filler products and to objectively evaluate their
`distinct characteristics.
`
`METIIO l >S
`Materials
`The HA dermal fillers tested were Restylanee and Pertanee (Medicis
`Aesthetics, Inc., Scottsdale, AZ); and Juwderm Ultra,• Juvederrn
`Ultra Plus• and Juveclerrn Volume• (Allergan, Inc., Irvine, CAI.
`
`

`

`JouRNJ\l. OF DRUGS IN DERMATOLOGY
`SEPTEMBER. 2011 • VOLUME 10 • ISSUE 9
`
`976
`D. Stocks, H . Sundaram, J. Michaels, et al.
`
`RGURE 1. Testing apparatus. The behavior of dermal fillers in response
`to applied shear forces was measured using a rotational or shear me(cid:173)
`ometer. Each gel was applied between two parallel circular plates. The
`actuator applied a variable rotational strain to each gel by oscillating at
`varying frequencies. The resistance of each gel to these applied forces
`was measured by the fixed transducer.
`
`TRANSDUCER
`
`PLATE~
`
`PIATE_/
`
`ACTUATOR
`
`Rheologic Methods
`The behavior of each gel in response to an applied shear force
`was measured using a rheometer (Rheometrics ARES; TA Instru(cid:173)
`ments Ltd., West Sussex, England). A sample of each gel was
`squeezed between two parallel circular plates and a variable
`rotational strain was applied to the gel by rotating one plate
`at varying frequencies while the other remained fixed (Figure
`1). The rheometer measures the resistance of the gel to these
`applied forces. To approximate the anticipated effects of facial
`muscle movement and gravity on implanted fillers, a gradually
`increasing shear force (measured in strain sweeps) was applied
`to each gel at a constant rate of 10 rads/sec (-1.6 Hz).
`
`Testing was performed within the linear viscoelastic range of
`each product, defined as the maximum amount of deformation
`each gel can withstand without changing its physical propar(cid:173)
`ties in an unpredictable and potentially irreversible manner.
`Increasing rates of deformation ( 1-100 rads/sec) at a fixed strain
`(frequency sweeps) were then applied to each gel followed im(cid:173)
`mediately by decreasing rates of deformation (100-1 rads/sec).
`During both procedures. the range and rates of deformation
`remained the same. The results of this experiment established
`the viscosity (G" and ri*), elasticity or firmness (G') and total
`resistance to deformation (G•) of each product.
`
`Using these data, the percent elasticity, or the extent to which
`each product returned to its original shape after deformation,
`was determined based on the relationship: percent elasticity •
`100 x G'/(G'+G"). The recovery coefficient was then calculated
`for each gel by dividing the viscosity value obtained during the
`increasing sweep frequency by the viscosity value obtained
`during the decreasing sweep frequency. Values for the recov(cid:173)
`ery coefficients were interpreted as follows (-"structure" refers
`to short• or medium-range interactions between molecules in a
`fluid by physical or chemical processes):
`
`• -1 = the gel retained its structure despite applied forces.
`
`• >1 " the gel experienced structural breakdown.
`
`• <1 a the gel experienced increased structure.
`
`Light Microscopy
`Light microscopy was performed using a Nikon SMZ-10A Ste(cid:173)
`reoscopic Zoom microscope (Nikon Corporation. Japan) to
`characterize the particulate nature of the gels with respect to
`particle size and distribution. To enhance visual contrast, some
`samples were diluted in water and stained with toluidin blue.
`
`IMMN•(cid:141) ~
`
`Restylane and Perlane were firmer than Juvederm Ultra, Juve-
`derm Ultra Plus and Juvederm Volume as demonstrated by higher
`elasticity modulus (G') and complex modulus (G•) values (Table
`2). The G' and G• for Restylane and Perlane were higher than that
`of Juvederm Ultra, Juvederm Ultra Plus and Juvederm Volume.
`Percent elasticity for Restylane and Perlane was also higher than
`for Juvederm Ultra and Juvederm Ultra Plus at both tested fre(cid:173)
`quencies but was highest for Juvederm Volume (Table 3). These
`five products demonstrate variable abilities to resist deformation
`and return to their original shape or •spring back" after a force has
`been applied. During controlled stress measurements. all samples
`behaved in a similar manner at stresses between 10 and 100 Pa.
`The recovery coefficients were found to be approximately 1 for all
`samples, meaning they retain their internal structure.
`
`TABLE 2.
`
`Elasticity and Complex Modulus at Test Frequency of 10 rads/sec
`
`Restylane
`
`Perlan•
`
`Juv6derm Ultra
`
`Juv6derm Ultra Plu•
`
`Juv6derm Volume
`
`G' (Pa)
`
`293.9
`
`337.9
`
`111.2
`
`159.2
`219.9
`
`301 .6
`
`344.4
`
`119.6
`
`168.9
`221.0
`
`Each experiment was performed at II fixed strain amplitude (1%1 and
`temperature 12,• CJ.
`
`

`

`joURNAl. OF DRUGS IN DERMATOLOGY
`SEPTEMBER 2011 • VOLUME 10 • ISSUE 9
`
`977
`D. Stocks. H. Sundaram, J. Michaels, et al.
`
`Photomicrographs illustrate that samples of Restylane and
`Perlane (Figure 2) both contain well-defined particles of very
`similar size with Perlane having larger-sized particles. Juve•
`derm Ultra, Juvederm Ultra Plus and Juvederm Voluma are
`also particulate in nature; however, their broader range of
`sizes make the particles in these products appear less ob(cid:173)
`vious under light microscopy due to the similar refractory
`indices of the HA particles and surrounding liquid phase (Fig•
`ure 3). Visualization of HA particles in a sample of Juvederm
`Volume with light microscopy was possible with the use of
`a staining technique. Toluidine blue revealed the particulate
`nature of this gel as shown in high• and low-magnification
`photomicrograph& (Figure 41.
`
`DISCUSSION
`Soft tissue augmentation with HA fillers has become one of
`
`RGURE 2. •·b• Photomicrographs of Restylane end Pertane. Photo•
`micrographs of Restylane and Pertane demonstrate the uniform size
`of the HA particles in each product. Each scale bar=10011M.
`
`the most commonly performed cosmetic procedures in the
`United States. 19 Advantages of HA dermal fillers include an
`excellent safety profile characterized by low immunogenic·
`ity following administration,,, durability, ,3.20 and reversibility
`with hyaluronidase.21 Additionally, Wang and colleagues dam•
`onstrated that the injection of a small gel particle HA filler
`(Restylanel stimulates natural collagen production that is pre(cid:173)
`sumed to be induced by the mechanicat stretching of the
`dermis and activation of dermal fibroblasts. 1° Current FDA•ap•
`proved indications for the use of HA fillers include soft tissue
`correction of moderate to severe facial rhytides and folds such
`as nasolabial folds; however, HA fillers are also commonly
`used for improvement of lip rhytides, marionette lines and
`nasojugal folds, lip filling and contouring, and chin and cheek
`augmentation.22 For these varied clinical applications, it may
`be beneficial to utilize HA filters that display a range of physi(cid:173)
`cal characteristics in order to meet individual patient needs.
`
`In this study, the higher G' and G• values for Restylaneand Perlane
`indicate that they are firmer gels and are able to resist deforma(cid:173)
`tion to a greater extent when a force is applied. These results
`are consistent with previously reported data demonstrating that
`Restylane and Perlane possess higher G' values than Juvederm
`Ultra and Juvederm Ultra Plus•.a (Table 41. Expressed as G• (Pal,
`other investigators also found the firmness of Restylane (306.6)
`and Perlane (334.51 to be greater than Juvederm Ultra (36.7) and
`Juvederm Ultra Plus (51.461.1 Although the absolute values for G"
`and G' vary across published reports, their relative magnitudes
`remain similar. As with any testing method or experiment dif(cid:173)
`ferences in reported values represent variations in the rheologic
`testing parameters such as the oscillation frequencies employed
`and the temperature at which testing was performed.
`
`In a recent publfcation comparing the lifting capacity of HA
`fillers, Borrell and colleagues concluded that Juvederm UI•
`tra and Juvederm Ultra Plus are able to achieve high lifting
`capacity by combining lower relative G' with higher "cohe(cid:173)
`sivity," which is described as "the tendency of a gel to stick
`together and hold its form or shape under stress".13 The au•
`thors use the term "cohesive• to describe greater crosslinking
`
`Percent Elasticity Test Frequency !rads/sec) -
`
`81.6
`
`83.9
`
`81.3
`
`83.6
`
`TABlE3.
`
`Restylane
`
`Perlane
`
`Juv6derm Ultra
`
`Juv6derm Ultra Plus
`
`72.9
`
`78.8
`
`71.7
`
`78.1
`
`Juv6derm Voluma
`88.8
`90.8
`Each experiment w,s performed (cid:127) t • fixed strain amplitude (1%) and
`temperature 124• Cl,
`
`

`

`JOURNAL OF DRUGS IN DERMATOLOGY
`SEPTEMBER 2011 • VOLUME to • ISSUE 9
`
`978
`D. Stocks, H . Sundaram, J. Michaels, et al.
`
`RGURE 3. a-b) Photomicrographs of Juvederm Ultra (top) and Juve(cid:173)
`derm Ultra Plus (bottoml. Although the average size of HA particles
`may be similar to Restylane and Perlane, they exist over a much
`broader range of sizes. Each scale bar-100 pM.
`
`TABLE 4.
`
`Elasticity Modulus {G') Determinations From Three Studies
`
`m'lalii@fiWlWNI
`
`Restylene
`
`Perlene
`
`588
`
`541
`
`860
`
`613
`
`JuvHerm Ultra
`
`Not Tasted
`
`28
`
`Juriderm Ultra Plus
`
`106
`Not Tested
`
`76
`274
`
`219.9
`'l<ebllk et el., 2009: "Sundaram et at., 2010; 'Present study. Note that these
`etudilll8 were perfotmed under varieble testing 00nditiont.
`
`293.9
`
`337.9
`
`111.2
`
`169.2
`
`harder or firmer gels'.3; however, we found that measure(cid:173)
`ments of G' were not exclusively related to cross-linking.
`Juvederm Ultra and Juvedarm Ultra Plus contain 24 mg/
`ml of HA24,25 which is 6-8% cross-linked. Nuclear magnetic
`resonance studies have shown that the mean proportion of
`cross-linking of the 20 mg/ml of HA contained in Perlane1'
`is approximately 1%.' No free or soluble HA is added during
`the manufacturing process to this family of dermal fillers,
`although some breakage of HA chains may occur during the
`manufacturing process of any gel resulting in the presence
`of small amounts of soluble HA.'
`
`As demonstrated by their higher values for elasticity modu•
`lus (G'I and complex modulus (G•), Restylana and Perlane are
`firmer than the Juvederm family of dermal fillers. Percent elas(cid:173)
`ticity values are calculated based on a ratio of G' and G" using
`the formula 100 x G'/IG'+G" ). Therefore, a gel with high G' and
`G" may have the same value for percent elasticity as a gel with
`low G' and G". Together, the fluid and particle components in
`Juvederm Volume as the finished product demonstrated great•
`er percent elasticity than the other fillers in this analysis due to
`the greater concordance between G' and G"; however, it is the
`elasticity of the gal particles alone which contributes to the lift
`effect of a HA dermal filler.
`
`The extent of HA modification also influences water absorption,
`which is inversely proportional to the degree of cross-linking.t>
`The physical properties of HA gel can be modified by the propor•
`tion of BODE molecules that attach two strands of HA together
`(cross-linked) and the proportion that are attached to only one
`strand of HA (pendant). Thus, the physical characteristics of each
`HA filler product and its clinical performance are not dependent
`on any single fBctor but result from a combination of numerous
`factors related to its manufacturing process. Newer HA fillers
`containing lidocaine to minimize patient discomfort during in(cid:173)
`jection, such as Restylane-L, Perlane-l, Juvederm Ultra XC and
`Juvedenn Ultra Plus XC are manufactured using processes that
`ensure homogenous distribution of the anesthetic without alter(cid:173)
`ing the physical properties of the products.11.21
`
`which holds the HA particles together and compensates for
`decreased l ifting capacity of a low G' gel. While a higher de•
`gree of crosslinking might confer benefits upon a HA filter in
`some clinical situations, the concept that this can alter the af(cid:173)
`fect of lower G' on lifting capacity is not supported by other
`studies reported in the literature.'·"' Additionally, the force
`and strain levels used for conducting the parallel plate and
`linear compression rheometry testing were not reported in
`this study, making interpretation of the results difficult.
`
`The extent of HA gel crosslinking or modification is ex(cid:173)
`pressed as the percentage of HA disaccharide monomer that
`is bound to crosslinker molecules. For example, 5% cross(cid:173)
`linking means that there are an average of five crosslinker
`molecules per 100 HA disaccharide monomers.3 An increase
`in the degree of modification has been reported to result in
`
`

`

`JOURNAL OF DRUGS IN DERMATOLOGY
`SEPTEMBER 201 I • VOLUME to • ISSUE 9
`
`979
`D. Stocks. H. Sundaram, J. Michaels, et al.
`
`RGURE 4. •·bl Photomicrographs of Juvederm Volume under high
`(top) and low (bottom} magnification. The particlute nature of the get
`is demonstrated using a toluidin blue staining technique. Left scale
`bar:50011M, right scale ber=1 mM.
`
`Photomicroscopy confirmed previous reports describing the
`particulate nature of the gels tested.' Although the average par(cid:173)
`ticle size was similar for the HA filler products tested here,' there
`was considerable variation in the distribution and range of par(cid:173)
`ticle sizes. The size of the HA particles in Restylane and Perlane
`is more uniform, while Juvederm Ultra,Juvederm Ultra Plus and
`Juvederm Voluma contain HA with a wide range of particle sizes.
`It is probable that these differences are due to the different pro(cid:173)
`cesses employed in the manufacturing of the products. Using
`laser diffraction techniques, other investigators have also dem(cid:173)
`onstrated that Juvederm Ultra and Juvederm Ultra Plus contain
`HA particles of more varied sizes.5
`
`on how they are used clinically.zw• The structural support and lift(cid:173)
`ing capacity of HA fillers that possess a high degree of firmness
`(G') and viscosity may be more desirable in treating deep folds
`and creating lift and volume while products that are less firm and
`viscous may be better suited for treating shallower folds and lines.
`Also, dermal fillers with greater viscosity and elasticity will tend to
`resist spreading after implantation.• Brandt and Cazzinga suggest
`using firmer HA dermal fillers for treating the glabella, cheeks,
`jawline, periocular and perioral areas while softer fillers may be
`more useful in treating the labiomental crease and lips.30
`
`U )NC:1.USJ<. )N
`
`The results of this rheologic study indicate that fiw commonly-used
`HA soft tissue fillers possess a range of physical properties, includ(cid:173)
`ing firmness and viscosity. Microscopy and staining confirmed the
`particulate nature of each product with varying ranges related to
`particle size and distribution. Although in vitro studies provide
`less direct evidence than comparative clinical trials, the objective
`methods employed in this study are of value to measure, describe
`and understand the physical attributes of HA soft tissue fillers. Ap(cid:173)
`preciation of these properties and their potential impact on clinical
`performance may better equip the clinician to select appropriate
`HA filler products based on patient needs and desired outcomes.
`
`,\CK NOW LEIH;I:/\1FNTS
`
`The authors acknowledge the assistance of Dr. Carl S . Horn(cid:173)
`feldt during the preparation of this manuscript.
`
`DISCLOSURES
`Th is study was sponsored by Medicis Aesthetics, Inc., Scottsdale,
`AZ.. USA. The rheological and microscopic analyses of samples
`in this study were performed by the independent laboratory ln(cid:173)
`tertek Measurement Science Group, Redcar, UK (David Stocks)
`with funding from Medicis Aesthetics Corporation, Scottsdale, AZ.
`
`Hema Sundarem, MD, has served as a consultant for, and has re(cid:173)
`ceived grants and/or research support from: Medicis Aesthetics
`Corporation, Scottsdale, AZ.; Mentor Worldwide, LLC, Santa Bar•
`hara. CA; Merz Aesthetics, Inc., San Mateo, CA; Suneva Medical,
`Inc., San Diego, CA.
`
`Jason Michaels, MD, has served as speaker and consultant for
`Medicis Aesthetics Corporation, Scottsdale, AZ. and as consul(cid:173)
`tant for Allergan, Inc., Irvine, CA.
`
`Mitchell S. Worttman, PhD and Diane B. Nelson, BSN, MPH are
`employees of Medicis Aesthetics Corporation, Scottsdale, AZ..
`Manzer J. Durrani, PhD, was an employee of Medicis at the time
`th is study was conducted.
`
`While the dermal filler products in this study demonstrated differ(cid:173)
`ent degrees of elasticity or firmness, viscosity, and distribution of
`particle size, the value of various dermal fillers ultimately depends
`
`R E FERE N C ES
`1. Kablik J, Monheit GD, Yu L. et al. Comparative physica1
`properties of hyaluronic acid dermal fillers. Dermatol Surg.
`
`

`

`JOURNAL OF DRUGS IN DERMATOLOGY
`SEPTEMBER 2011 • VOLUME 10 • ISSUE 9
`
`980
`D. Stocks, H. Sundaram, J. Michaels, et al.
`
`2009;35:302-312.
`2. Bogdan Allemann I, Baumann L. Hyaluronic acid gel (Juve(cid:173)
`derm) preparations in the treatment of facial wrinkles and
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`
`ADDRESS FOR CORRESPONDENCE
`
`Diane B. Nelson, BSN, MPH
`Medicis Pharmaceutical Corporation
`7720 North Dobson Road
`Scottsdale, AZ. 85256
`Phone: .................................................................. 1480) 291-5826
`Fax: ...................................................................... (480) 291-8826
`E-mail: .................... ·········--· .. ··· .. ······ ........ dnelsonOmedlcis.com
`
`