Illustrated Manual of

Injectable Fillers
Series in Cosmetic and Laser Therapy
About the Series
The world of cosmetic and aesthetic medicine and surgery has grown greatly in size and complexity
over recent years, and the series in Cosmetic and Laser Therapy keeps readers up to date with the latest
clinical therapies to improve and rejuvenate the appearance of skin, hair, and nails. Published in as-
sociation with the Journal of Cosmetic and Laser Therapy, each volume in the series is prepared
separately and typically focuses on a topical theme. Volumes are published on an occasional basis,
according to the emergence of new developments.

Handbook of Cosmetic Skin Care, Second Edition

Avi Shai, Howard I. Maibach, Robert Baran

Cosmetic Bootcamp Primer: Comprehensive Aesthetic Management

Kenneth Beer, Mary P. Lupo, Vic A. Narurkar

Illustrated Manual of Injectable Fillers: A Technical Guide to the Volumetric Approach to Whole
Body Rejuvenation, First Edition
Neil S. Sadick, Paul J. Carniol, Deborshi Roy, Luitgard Wiest

Comprehensive Aesthetic Rejuvenation: A Regional Approach

Jenny Kim, Gary Lask, Andrew Nelson

Textbook of Chemical Peels: Superficial, Medium, and Deep Peels in Cosmetic Practice, Second
Edition
Philippe Deprez, Philippe Deprez

Textbook of Cosmetic Dermatology, Fifth Edition

Robert Baran, Howard I. Maibach

Disorders of Fat and Cellulite: Advances in Diagnosis and Treatment

David J. Goldberg, Alexander L. Berlin

Botulinum Toxins in Clinical Aesthetic Practice 3E, Volume Two: Functional Anatomy and
Injection Techniques
Anthony V. Benedetto

Botulinum Toxins in Clinical Aesthetic Practice 3E, Volume One: Clinical Adaptations
Anthony V. Benedetto

Botulinum Toxins in Clinical Aesthetic Practice 3E: Two Volume Set

Anthony V. Benedetto

Aesthetic Rejuvenation Challenges and Solutions: A World Perspective

Paul J. Carniol, Gary D. Monheit

Illustrated Manual of Injectable Fillers, Second Edition

Neil S. Sadick

For more information about this series please visit: [Link]

Laser-Therapy/book-series/CRCCOSLASTHE
 Illustrated Manual of
Injectable Fillers
Second Edition

Edited by
Neil S. Sadick, MD, FAAD, FAACS, FACP, FACPh
Medical Director, Sadick Dermatology, New York, NY, USA
Second edition published 2021
by CRC Press
6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742
and by CRC Press
2 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN
CRC Press is an imprint of Taylor & Francis Group, LLC
First edition published by CRC Press 2011
© 2021 Taylor & Francis Group, LLC
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted,
reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means,
now known or hereafter invented, including photocopying, microfilming, and recording, or in any
information storage or retrieval system, without written permission from the publishers.
For permission to photocopy or use material electronically from this work, access www.
[Link] or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive,
Danvers, MA 01923, 978-750-8400. For works that are not available on CCC please contact
mpkbookspermissions@[Link]
This book contains information obtained from authentic and highly regarded sources. While all
reasonable efforts have been made to publish reliable data and information, neither the author[s]
nor the publisher can accept any legal responsibility or liability for any errors or omissions that
may be made. The publishers wish to make clear that any views or opinions expressed in this
book by individual editors, authors or contributors are personal to them and do not necessarily
reflect the views/opinions of the publishers. The information or guidance contained in this book is
intended for use by medical, scientific or health-care professionals and is provided strictly as a
supplement to the medical or other professional’s own judgement, their knowledge of the
patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice
guidelines. Because of the rapid advances in medical science, any information or advice on
dosages, procedures or diagnoses should be independently verified. The reader is strongly urged
to consult the relevant national drug formulary and the drug companies’ and device or material
manufacturers’ printed instructions, and their websites, before administering or utilizing any of
the drugs, devices or materials mentioned in this book. This book does not indicate whether a
particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole
responsibility of the medical professional to make his or her own professional judgements, so as
to advise and treat patients appropriately. The authors and publishers have also attempted to trace
the copyright holders of all material reproduced in this publication and apologize to copyright
holders if permission to publish in this form has not been obtained. If any copyright material has
not been acknowledged please write and let us know so we may rectify in any future reprint.
Trademark notice: Product or corporate names may be trademarks or registered trademarks and
are used only for identification and explanation without intent to infringe.

ISBN: 978-1-138-73395-4 (hbk)

ISBN: 978-1-315-18743-3 (ebk)

Typeset in Times
by MPS Limited, Dehradun
Contents

List of contributors .................................................................................................................................. vii

1. Introduction to Structural Volumetric Rejuvenation ..................................................................1

Neil S. Sadick
2. Filler Biologic Properties and Techniques ....................................................................................7
Neil S. Sadick
3. Choosing an Ideal Filler for Your Patient ..................................................................................15
Cheryl Karcher
4. Anatomy of the Forehead and Periocular Region .....................................................................23
Marcelo B. Antunes and Stephen A. Goldstein
5. Volumetric Approach to the Upper Face....................................................................................29
Deborshi Roy and Sachin M. Shridharani
6. Anatomy of the Midface ................................................................................................................35
Stephen A. Goldstein and Evan Ransom
7. Volumetric Approach to Midfacial Rejuvenation ......................................................................43
Robert A. Glasgold, Justin C. Cohen, Mark J. Glasgold, Sachin M. Shridharani,
and Jason D. Meier
8. Anatomy of the Lower Face and Neck........................................................................................61
Evan Ransom and Stephen A. Goldstein
9. Volumetric Approach to Lower Facial Rejuvenation................................................................67
Robert A. Glasgold, Justin C. Cohen, Mark J. Glasgold, Sachin M. Shridharani,
and Jason D. Meier
10. Volumetric Approach to the Lips ................................................................................................79
Mary P. Lupo and Amanda A. Lloyd
11. Hand Augmentation Using Injectable Fillers .............................................................................97
Sachin M. Shridharani, Teri N. Moak, Trina G. Ebersole, and Grace M. Tisch
12. Injectable Poly-L-Lactic Acid for the Arms ..............................................................................111
Daniel Dal’Asta Coimbra and Betina Stefanello
13. Using Fillers in the Abdomen and Buttocks .............................................................................121
Rosemarie Mazzuco and Taciana Dal’Forno Dini
14. Using Fillers to Treat Cellulite ...................................................................................................133
Rosemarie Mazzuco and Taciana Dal’Forno Dini
15. Complications of Fillers and Their Management ....................................................................143
Macrene Alexiades
16. Combination Approaches: Using Fillers With Toxins and Energy-Based Devices .............155
Sabrina Fabi and Natalie Yin

Index ...................................................................................................................................................... 173

v
List of Contributors

Macrene Alexiades, Yale University School of Medicine, New Haven, CT, and Dermatology and Laser
Surgery Center of New York, NY, USA
Marcelo B. Antunes, The Piazza Center, Austin, TX, USA
Justin C. Cohen, West End Plastic Surgery, Washington, DC, USA
Daniel Dal’Asta Coimbra, Les Peaux Clinic, Rio de Janeiro, Brazil
Taciana Dal’Forno Dini, Hospital São Lucas da PUCRS, Porte Alegre, Brazil
Trina G. Ebersole, Washington University in St. Louis, St. Louis, MO, USA
Sabrina Fabi, Cosmetic Laser Dermatology, San Diego, CA, USA
Mark J. Glasgold, Glasgold Group, Princeton, NJ, USA
Robert A. Glasgold, Glasgold Group, Princeton, NJ, USA
Stephen A. Goldstein, Banner University Medicine Multispecialty Surgery Clinic, Tucson, AZ, USA
Cheryl Karcher, Center Aesthetic, New York, NY, USA
Amanda A. Lloyd, The Skin and Vein Institute, Encinitas, CA, USA
Mary P. Lupo, Lupo Center for Aesthetic and General Dermatology, New Orleans, LA, USA
Rosemarie Mazzuco, Private Practice, Carazinho, RS and Rondonopolis, MT, Brazil
Jason D. Meier, ENT Specialists of North Florida and Meier Plastic Surgery, Jacksonville, FL, USA
Teri N. Moak, Washington University in St. Louis, St. Louis, MO, USA
Evan Ransom, San Francisco Facial Plastic Surgery, San Francisco, CA, USA
Deborshi Roy, Ear Nose Throat & Sinus Center, Rancho Cucamonga, CA, USA
Neil S. Sadick, Medical Director, Sadick Dermatology, New York, NY, USA
Sachin M. Shridharani, LUXURGERY, New York, NY, USA
Betina Stefanello, Instituto de Dermatologia Prof. Rubem David Azulay, Rio de Janeiro, Brazil
Grace M. Tisch, LUXURGERY, New York, NY, USA
Natalie Yin, Dermatology, Pfizer, New York, NY, USA

vii
1
Introduction to Structural Volumetric
Rejuvenation

Neil S. Sadick

Cosmetic Surgery Trends

Non-invasive and minimally invasive procedures have rapidly changed the face of aesthetic medicine.
Cannulas, needles, and syringes have replaced the scalpel, and lunchtime treatments have eradicated the
need to take time off work for recovery. There is always momentum in the field, and clinicians are
constantly testing and developing new strategies to offer to their aesthetic patients. Because men and
women from every culture, age group, and ethnicity seek aesthetic treatments, intimate knowledge of
anatomical differences between genders and across cultures, together with the ability to adapt to and
adopt the ever-changing armamentarium of clinical tools is an absolute necessity.
As opposed to past trends, where an ironed-out look was sought after, today there has been a shift in
the perception of what constitutes a youthful appearance. The new movement has been about con-
servative approaches that deal with the underlying loss of soft tissue to achieve a plumper, naturally less
wrinkled, more three-dimensional appearance. This shift in the perception of what constitutes a
“youthful visage,” combined with patient demand for minimally invasive procedures, has led to a major
expansion in the field of soft tissue augmentation.
The facial aging process reflects an interplay of genetic, anatomic, chronologic, and environmental
factors. It is characterized by thinning of the epidermis and subcutaneous fat layers, musculature atrophy,
and a degree of bone resorption. In addition, a progressive loss of elastic fibers and collagen and weak-
ening of underlying muscles contribute to the wrinkling process. Age associated changes can create
shadows and hollows where they did not exist before. The aged face has prominent rhytids in the glabella,
forehead, nasolabial folds (NLFs), and perioral areas. Today, dermatologic surgeons can approach these
conditions of atrophic aging with autologous fat, or a variety of new-generation volumetric fillers.
Volumetric structural rejuvenation offers an excellent option for the treatment of facial aging,
wrinkling, and contour defects. It is a preferred alternative to major surgery for patients seeking safe,
minimally invasive, and affordable means of maintaining a youthful appearance. It is imperative
however for the physician to have a thorough knowledge of all the available products and their prop-
erties. This knowledge will enable optimal pairing of facial filling techniques with specific concerns and
consequent maximal efficacy and patient satisfaction.

Evolution of the Field

Historically, significant volume enhancement has been available through the surgical use of alloplastic
implants. The exact origin of maxillofacial prosthetics is difficult to identify but major work in the
1930s provided the initiative for maxillofacial, dental, and plastic surgeons to work together for the
2 Illustrated Manual of Injectable Fillers

betterment of focally injured patients. Today, the techniques that have evolved from those early trials
have become safe and applicable in situations where even minimal deformity is present.
Transferring fat from one area of the body to another has revolutionized the trend of rejuvenation by
volume restoration and it can be said that fat was the first available filler. There has been interest in fat transfer
since the inception of whole fat grafts in the 1890s and injectable fat grafts in the 1920s. From then on,
interest waned until the 1980s when interest once again boomed in the plastic surgery community. The rising
popularity of this procedure has paralleled the development and popularity of liposuction for body contouring.
Autologous fat is plentiful and readily accessible once the harvesting technique is mastered. The
technique is intended to preserve the delicate structure of adipocytes and provide a robust blood supply on
which fat cells are extremely dependent. Fat provides excellent volumetric filling and the possibility of
long-term results exceeding that of resorbable fillers. Patients’ satisfaction with fat is high and many prefer
using their own autologous fat rather than synthetic fillers. Autologous fat can also offer benefits to the
skin quality, improving acne, scarring, and providing a healthy luster. Whether this phenomenon is due to
nutrients in the fat cells or “stem cell” characteristics, as has been proposed, is purely theoretical.
Some practitioners believe that fat transfers represent one of the most significant rejuvenation advances
of the decade. Volumetric facial rejuvenation is excellent for the forehead, eyes, cheeks, chin, myelolabial
lines, lips, marionette lines, and geniomandibular grooves. In the body, large-volume fat transfers can be
used in the buttocks, breasts, calves, and for posttraumatic or iatrogenic liposuction defects. Ongoing
interest in fat transfer and constant reassessment of clinical results will lead to further improvements in the
procedure of fat transfer for soft tissue volumization and augmentation.

Injectable Fillers
The practice of using injectable fillers for soft tissue augmentation has a long and well described history.
Today it is a crucial tool in the armamentarium of facial volumization.
Over the past decade, the use of injectable products in cosmetic dermatology has increased rapidly to
become, together with neurotoxins, the most popular cosmetic procedure performed in physicians’
offices. Over the past few years, the search for an ideal filling agent has led to a plethora of available
materials for facial rejuvenation. The ideal filler substance would be nonallergic, noncarcinogenic,
nonteratogenic, durable, reproducible, stable, and affordable, and would cause minimal adverse events.
Arguably, for some the ideal filler will be permanent and for others resorbable, depending on the
patient’s prior experiences and the physician’s expertise. Although a filling material that satisfies all of
the above criteria is yet to be found, there are numerous compounds that fall just short of doing so and
are safely and easily administered in the office setting. The choice of filling substance depends on the
depth of the target to be treated as well as various patient factors. It is important for the injector to be
judicious, always informing patients of the risks and benefits of treatment and advocating appropriate
test doses, if necessary, to avoid or minimize potential adverse events.
In the 1980s, the use of bovine collagen for cosmetic purposes started a new era of soft tissue augmentation.
Over the past 5 years alone, the number of approved facial fillers in the US and abroad has grown rapidly. To
date, the most widely used fillers fall into three major categories: nonpermanent, permanent, and semi-
permanent. Nonpermanent fillers produce short-lived results and eventually undergo resorption. Fillers of this
type will require repeated injections for long-term results. Semipermanent fillers typically last longer than
most nonpermanent fillers but can be expected to experience some resorption as well. Only permanent fillers
can be expected to produce long-term results with a single injection.

Short -Term Fillers

Collagens
Collagen is a major component of human connective tissues such as bone, cartilage, skin, and vascu-
lature. The injectable forms consist of varying concentrations of purified bovine, porcine, or human
Introduction to Structural Volumetric Rejuvenation 3

collagen. Bovine collagen was the first US Food and Drug Administration (FDA)–approved facial filler
in 1981 and was harvested from an isolated US herd. One major disadvantage of bovine collagens
(Zyderm, Zyplast) is their potential for immunogenicity and mandatory skin testing. Improving on the
issue of allergic reactions are human (CosmoDerm, CosmoPlast) and porcine (Evolence) collagens. At
the time of this writing, all of these fillers have been removed by the manufacturer from the US market;
however, the potential remains for a porcine filler to be reintroduced. All collagen fillers are biode-
gradable and resorbable with results lasting less than 1 year. Slowing of collagen resorption (prolonged
filler effect) is accomplished by crosslinking the collagen with moieties such as glutaraldehyde or
ribose. Rapid degradation is not necessarily a drawback to collagen products; indeed, it is an asset under
some aesthetic requirements. Collagens are best suited for superficial correction and are injected into the
dermal plane. Rapid polymerizing collagen (RPC Pure-Collagen, EternoGen) is a new iteration of
collagen that has been evaluated in US and European clinical trials. It consists of pure type I collagen
molecules (un-crosslinked, sterile, non-pyrogenic, porcine derived), ethylenediaminetetraacetic acid
(chelating and antimicrobial agent), and mannitol, an antioxidant to reduce free radical activity from the
treatment site.

Hyaluronic Acid
Hyaluronic acid (HA) fillers are particularly popular because they have a low potential for allergic
reaction and require no skin testing. Although they are not permanent, most of these agents have a
significant length of duration. As of the start of 2017, there are 14 US FDA-approved HA fillers:
Restylane (-L, Lyft, Refyne, Defyne, Silk), Juvederm (Ultra, Ultra XC, Plus, Plus XC, Voluma,
Voluma XC, Vollure XC, Volbella XC), and Belotero Balance. At the time of publication a new HA
filler, Teosyal (Teoxane), that earned US FDA approval in late 2017 is expected to be available in the
US from early 2020.
HA is a naturally occurring glycosaminoglycan that composes the extracellular matrix of con-
nective tissues. In the skin, it provides structure and volume while also maintaining and attracting
moisture. As the skin ages, the amount of HA decreases and correlates with the formation of rhytids.
Clinically, the injection of HA into the skin replenishes volume and revitalizes the skin’s appearance.
Most HAs on the market are non-animal-stabilized HAs and are manufactured by the fermentation of
Streptococcus equi bacterium. Most of the products differ in the total HA concentration and degree of
crosslinked material. The total HA concentration refers to the measure of insoluble HA and soluble
HA in a product. The soluble of liquid form of HA is absorbed very quickly and is added to some
products to improve lubrication and flow through the needle. The insoluble gel portion that persists in
the skin after injection contributes to the clinical effect. All of the currently available HA fillers are
indicated by the FDA for injection into the mid to deep dermis for the correction of either moderate to
severe facial wrinkles and folds, specifically NLFs, or in the lips. However, HA products are routinely
used for off-label indications.

Intermediate to Long-Term Fillers

Calcium Hydroxylapatite
Calcium hydroxylapatite (CaHA), long used as a bone replacement, lends itself well to soft tissue
augmentation. Its high density and low solubility provide a long-term effect with minimal immune
sensitivity. Radiesse™ is the only FDA-approved CaHA dermal filler. It is a viscous gel, composed of
carboxymethylcellulose, glycerine, and purified water, within which 25–45 µm spherical particles
of CaHA are suspended. Radiesse is considered a medium- to long-term volumizer with duration of
effect being reported to last over 12 months. Additionally this filler has been found suitable for
diverse locations. In addition to volumizing the cheeks and NLFs, Radiesse is utilized for nose and
chin augmentation as a panfacial volumizer and contouring agent. Radiesse was approved for usage in
the dorsum of the hands in 2015.
4 Illustrated Manual of Injectable Fillers

Polycaprolactone
Polycaprolactone (PCL), presently in phase 3 trials, is demonstrating to be a much stronger biostimulatory
filler than CaHA. The collagen produced by PCL is more stable, so PCL lasts longer than CaHA. The
product called Ellansé comes in four types, S, M, L, and E, which last 1, 1.5, 3, and 4 or more years,
respectively.

Poly-L-Lactic Acid
Poly-L-lactic acid (PLLA) is a synthetic material used in resorbable sutures, plates, and screws. PLLA for
injection is available as Sculptra, a powered form of PLLA in microspheres of 40 to 63 µm in diameter,
which must be reconstituted with sterile water prior to injection. PLLA is categorized as a bioactive filler
due to its ability to stimulate neocollagenesis. PLLA was initially FDA approved for HIV lipoatrophy
correction but was frequently used off-label for other cosmetic concerns. In July 2009, Sculptra was
approved for aesthetic indications by the FDA. It is primarily utilized for diffuse global correction rather
than individual rhytids and often requires multiple sessions for desired results. Correction is not immediate
and requires 3–6 months as fibroblasts are stimulated to produce new collagen and dermal remodeling
occurs. In addition to volumization, PLLA was recently shown to improve skin quality.

Permanent Fillers
Currently only one filler, Bellafill (previously ArteFill), is FDA approved for permanent correction.
Bellafill is composed of polymethyl methacrylate microspheres in a bovine collagen carrier. The
nondegradable microspheres serve to stimulate fibroblast activity and connective tissue ingrowth giving
this filler a biostimulatory property. The end result is a biologically stable matrix that creates a durable,
long-lasting cosmetic enhancement. An essential key to successful Bellafill use is a conservative ap-
proach with avoidance of overcorrection. The FDA approved the use of Bellafill for correction of NLFs
in 2005 and for the correction of moderate to severe, atrophic, distensible facial acne scars on the cheek
in 2015 for patients over the age of 21 years.

Other Considerations
Although injectable fillers can offer an efficacious alternative to surgery, they also have their limitations.
It is important for the plastic surgeon to recognize specific circumstances that may be best managed with
an alternative to fillers, including superficial contour defects too shallow for fillers; areas with significant
skin laxity in which filler injection may result in lumpiness; and deep defects or folds in areas of
dynamic movement, which may result in filler dislodgement or visible filler implants.
Appropriate and complete training is critical for success with all fillers. Indeed training is often a
regulatory requirement associated with treatment. Choosing a dermal filler for a particular defect is
perhaps more an art than science, with few hard and fast rules. Most products have been studied only in
the NLFs, but are used in many other applications; thus experience remains the best teacher. Table 1.1
lists some general-use criteria for dermal filler products that are further discussed in later chapters.
Short-term volumizers such as collagen and HA fillers are best used for superficial, smoothing appli-
cations. The longer lasting stimulatory fillers are beneficial for deeper contouring in areas where a more
significant tissue response is instrumental in achieving the desired effect.
Dermal fillers are labeled for injection at specific dermal depths. In general, the more viscous and
thick the product, the deeper it is to be injected. Care must be taken in thin-skinned areas, such as the
glabellar lines, and the lips (especially the vermillion border), which may be prone to vascular occlusion
and necrosis, or may result in exaggerated protrusion. The literature is full of the trials and wisdom of
the pioneers in this field of ever-expanding technology and increasing refinement of technique. It
is imperative to refer to the medical annals and to remain updated on the evolving indications and
recommendations of usage.
Introduction to Structural Volumetric Rejuvenation 5

TABLE 1.1
Typical Uses of Dermal Fillers
Hyaluronic acids Deep and superficial placement depending on anatomical area (nasolabial fold vs. lips)
Radiesse Deeper folds; deep dermal/supraosteal placement
Sculptra Deep placement; panfacial volumizer, hands
Bellafill Permanent in deep to mid dermis

Conclusion
The field of aesthetic volumization has grown considerably from the humble beginnings of bovine
collagen over 20 years ago. The ease and effectiveness of fillers have led to great patient acceptance and
demand. Today there are many choices driven by powerful marketing campaigns that have patients
rushing to try the latest filler available. The race is on and the search will continue for better and more
appropriate injectables that will allow cosmetic surgeons and dermatologists to offer a broad scope of
therapeutic combinations. It has been said that a millimeter of improvement on the face is a kilometer in
the soul. Although improvement may be transient, patients are very often gratified at turning back the
clock, however temporarily. Volume filling in the face has moved on to other anatomic locations, such
as the hands, décolleté, breasts, and buttocks. The combination approach with neurotoxins and anato-
mically tailored filler placement has allowed for the emergence of the “liquid facelift,” the epitome of
noninvasive rejuvenation. Thanks to the success, safety, and ongoing research into dermal fillers, it is an
exciting time for cosmetic surgeons, the industry, and most importantly our patients.
2
Filler Biologic Properties and
Techniques

Neil S. Sadick

Introduction
Our world is changing every day, but the desire to look younger remains the same. Technological
advancements coupled with an explosion in the public’s interest in minimally invasive procedures have
led to a major increase in the use of injectable fillers. Fillers that were used a decade ago are no longer
on the market, and new-generation fillers are continuously being developed alongside an increased
understanding of their ideal use.
Liquid silicone was the first filler available in the US to treat contour defects, scars, and rhytides of
the face. It was widely used for two decades until concerns about long-term safety caused it to fall out
of grace (1,2). Bovine collagen was the second available injectable filler and was widely used with a
high incidence of allergic reaction complications (3).

Currently Available Fillers and Their Biologic Properties

Autologous fat, hyaluronic acid (HA), calcium hydroxylapatite (CaHA), poly-L-lactic acid (PLLA), and
polymethyl methacrylate (PMMA) are currently the most frequently used fillers for volumetric struc­
tural rejuvenation. These agents differ in their longevity, biologic activity, and ability to volumize and
hydrate the tissue.

Autologous Fat Transfer

Autologous fat transfer techniques were introduced around the same time as bovine collagen. The safety
of using autologous material cannot be matched by any foreign body, animal or synthetic. However,
there is an increased morbidity associated with this more invasive type of procedure that requires a
separate harvesting and administration. Given the fat anatomy, large (over 18-gauge) cannulas are
required for injections. A variety of factors, including the harvesting technique, type of fat implanted,
treatment site, injection technique, and experience of the injector can influence the efficacy of treatment.
Consistent, reproducible results have also become an obstacle for some practitioners. Autologous fat is
harvested from the donor site via tumescence but loses its hydration after injection to the recipient site.
After transplant, although there is localized fibroblast activation and neocollagenesis, no additional
water retention is observed. Regarding the longevity of transplanted fat, it is estimated to be retained
from 20 to 80% (4–6). New processing techniques such as the addition of platelet-rich plasma or
adipose-derived stem cells to transplanted fat are currently being evaluated to improved viability and
longevity of autologous fat injections (7,8).

7
8 Illustrated Manual of Injectable Fillers

Hyaluronic Acid
HA fillers are the most popular, most widely used nonsurgical cosmetic treatments. The various
preparations currently available in the US differ in crosslinking and concentration of HA in the carrier
vehicle (Table 2.1). In liquid formulations, it is used to fill small, superficial wrinkles, giving the skin
elasticity and flexibility, while crosslinked preparations are used for the correction of facial contours.
Although the products are all similar, there are subtle differences that lead each injector to have his or
her own preference, depending on the product’s rheological properties, site of injection, and longevity
(9–11). For volume replacement, preparations with concentrations of 20–24 mg/mL are used. The
primary clinical endpoint of HA injections has been a space-filling effect of HA, although as a hy­
drophilic molecule it also leads to marked water retention generated by osmosis. This water retention
leads to a biological change in the atrophied subcutaneous tissues, wherein the rehydration at the
site of injection is followed by a secondary redistribution of subcutaneous fluids and water bound to
HA molecules. Moreover, the mechanical tension on fibroblasts, which has been associated with
the regulation of collagen synthesis, stimulates neocollagenesis, augmenting the clinical effect of the
filler (12).

Calcium Hydroxylapatite
CaHA (Radiesse) is composed of synthetic, uniform, and smooth CaHA microspheres suspended in an
aqueous carboxymethylcellulose gel carrier (Table 2.2). The US Food and Drug Administration
(FDA)–approved uses of Radiesse include the correction of moderate to severe facial folds and wrinkles
such as nasolabial folds (NLFs), and the correction of facial lipoatrophy in patients with human im­
munodeficiency virus (HIV) infection. Radiesse is a biostimulatory filler, as once injected into the skin,
the carrier gel is gradually resorbed and the remaining CaHA microspheres stimulate the local pro­
duction of endogenous collagen (13). Eventually, the microspheres are degraded into calcium and
phosphate ions and are excreted. This is a bulkier product than those previously mentioned and is
injected into a deeper plane. The unique viscosity and elasticity of the material make it possible to mold
the implant for several minutes after injection, minimizing irregularities in contour. Results last from 8
to 12 months after injection.

TABLE 2.1
Hyaluronic Acid Fillers in the US
Trade Name HA Conc., mg/mL Type Lidocaine Needle Size, G
Belotero Balance 22.5 Cohesive poly-densified matrix HA No 27 or 30
Juvederm Ultra 24 Hylacross HA No 30
Juvederm Ultra XC Yes
Juvederm Ultra Plus 24 Hylacross HA No 27
Juvederm Ultra Plus XC Yes
Juvederm Volbella 15 Vycross HA Yes 30
Juvederm Voluma 20 Vycross HA No 25 or 27
Juvederm Voluma XC Yes
Restylane 20 NASHA No 30
Restylane-L Yes
Restylane Silk Yes
Restylane Lyft 20 NASHA Yes 27 or 29
Restylane Refyne 20 XpresHAn Yes 30
Restylane Defyne 20 Yes 27
Filler Biologic Properties and Techniques 9

TABLE 2.2
Non-Hyaluronic Acid Fillers in the US
Trade Name Source Particle Size (diameter) Lidocaine Needle Size, G
Sculptra aesthetic PLLA 40–63 μm microspheres No 26
Radiesse CaHA 25–45 μm microspheres No 25–27 ID
Radiesse (+) Lidocaine Yes 27 ID
Bellafill (previously ArteFill) PMMA 30–50 μm microspheres Yes 26

Upper Third
(Trichion)

Middle Third
(Glabella)

Lower Third
(Menton)

FIGURE 2.1 Facial mapping for filler injections in thirds. Common concerns of the upper third: forehead contour,
temple fullness, brow shape; middle face: lateral/medial cheek, under eye, nose contour; lower face: jawline, lips, chin,
marionette lines, submalar cheek hollow.

Sculptra
Sculptra is a suspension of PLLA in water (Table 2.2). It is FDA approved for the treatment of HIV-
associated lipoatrophy, the correction of shallow to deep NLF contour deficiencies, and other facial
wrinkles. Like CaHA, this filler has biostimulatory properties so once injected, it induces a subclinical
inflammatory response that stimulates fibroblast proliferation and collagen formation, leading to a
progressive increase in volume of the dermis. Eventually, PLLA is gradually degraded over the course
of 9–24 months (14,15). As opposed to a single-injection session, multiple injection sessions several
weeks apart must be utilized. Because treatment results progressively improve over time, under­
correction of the defect is the goal. Of note, transient tissue edema may develop immediately after
injection, resulting in the appearance of full correction. Subsequent treatments should be spaced by at
least 3 weeks to allow for assessment of response.

Bellafill Polymethyl Methacrylate

Bellafill (previously ArteFill) is the only nonbiodegradable injectable filling agent in North America. It
is composed of 30–50 μm PMMA microspheres suspended in a water-based gel containing 3.5% bovine
collagen and 0.3% lidocaine (Table 2.2) (16,17). Bellafill is currently approved by the FDA for NLFs
and acne scars (18,19). After implantation, the bovine collagen component of Bellafill dissipates over
the course of 1–3 months, leaving behind the nonbiodegradable PMMA microspheres. The
10 Illustrated Manual of Injectable Fillers

FIGURE 2.2 Serial puncture. Insert needle into skin ≈10 degree parallel to length of wrinkle/fold. Place series of
injections close together to create a smooth, uniform result. Gently massage injection site with a finger or roll cotton swab
over area. (By courtesy of Dr. Deborshi Roy.)

FIGURE 2.3 Lineal threading. Insert full length of needle into skin ≈30 degree parallel to length of wrinkle/fold. Deposit
filler linearly as you insert (antegrade) or withdraw (retrograde) needle. Gently massage injection site with a finger or roll
cotton swab over area. Serial threading is a combination of serial puncture and linear threading techniques. (By courtesy of
Dr. Deborshi Roy.)

microspheres stimulate a local inflammatory reaction that is followed by the deposition of granulation
tissue during the first few weeks after implantation. The connective tissue subsequently matures, and by
3 months after injection, PMMA microspheres are surrounded by newly formed collagen. The presence
of new collagen accounts for the observed volume-filling effect (20). Bellafill is supplied in prefilled
syringes, and product should be implanted in the deep reticular dermis using a 26-gauge needle.
Typically a series of conservative injections is required to achieve optimal results, and touch-up in­
jections can be performed 1–3 months after the initial treatment. Because new collagen synthesis
contributes to the effect, optimal results occur after approximately 3–12 months.

Basics of Treatment Planning

Careful evaluation and proper diagnosis is critical for a favorable outcome. We analyze the entire
anatomic area including the skin, subcutaneous tissue, muscle, fat, and bone. A global appreciation for
the proportion and geometry of the area as a whole and the harmony between aesthetic subunits helps to
produce the finishing touches to volumetric rejuvenation.