The biostimulatory injectable fillers poly-l-lactic acid and calcium hydroxylapatite have numerous indications and are increasingly used by dermatologists for novel applications. Initially approved for the treatment of HIV-associated lipoatrophy, their stimulation of collagen synthesis leads to a filling effect with long-lasting results. As such, they can be used for numerous cosmetic purposes including wrinkles, scars, and body contouring. In this review, we discuss the biological properties and indications for these two fillers, as well as our experience and technique in using them to treat cellulite and in gluteal enhancement.
Since the late 1990’s, the biostimulatory
injectable fillers Poly-L-Lactic Acid (PLLA) and Calcium Hydroxylapatite (CHA)
have been used for cosmetic purposes such as treating wrinkles, improving skin
volume, and treating scar lesions . Unlike
exogenous collagen, silicone, or fat injections, these fillers induce an immune
reaction that leads to the deposition of new collagen fibers with longer
lasting results for the patient [2,3]. Both
Poly-L-Lactic acid (Sulptra™) and
Calcium Hydroxylapatite (Radiesse™)
were initially developed and FDA approved for treating HIV-associated
lipoatrophy of the face with positive results [3,4].
Soon after their release, many dermatologists began using them off-label for
various other cosmetic issues. Recently, both products have been approved by
the FDA for the treatment of facial wrinkles and nasolabial fold contour
deficiencies . Their efficacy in treating
acne and varicella scars, chest wall deformities, stretch marks, and skin
laxity in the upper arms, thighs, abdomen, dorsal hand, and neck is also being
investigated [6-11]. However, there is a paucity
of literature demonstrating the use of either of these injectables for the
treatment of cellulite or for gluteal enhancement. The goal of this article is
to investigate their properties and their possible effectiveness in managing both
of these issues, and to describe a gluteal enhancement procedure that has shown
promising results in our patients.
Properties and the Changes Seen in Aging Skin
To better understand why these injectables
have demonstrated success in treating various cosmetic issues, it is necessary
to have a basic understanding of collagen’s role in healthy skin and the
changes that take place in aging skin. Collagen is important for maintaining
the structure and tensile strength of not only the skin but of all connective
tissue in the body and is needed for the support of the biomechanical function
of these tissues . In the skin,
specifically, type I collagen fibrils provide the mechanical stability and attachment
sites for fibroblasts, the cells that produce more collagen . The superficial fascia is a collagenous
structure which maintains the separation of the two layers of subcutaneous fat.
It has been suggested to be involved in the pathogenesis of numerous cosmetic
issues, including cellulite [14,15].
Aging skin and wrinkles are the
result of a loss of tone and elasticity in the skin over time secondary to a
myriad of factors including smoking and sun exposure .
Changes in the skin associated with wrinkles include increased skin laxity,
gravitational forces on the soft-tissue, loss of both muscle and fat volume,
changes in fat distribution, erosion of bony landmarks, slower skin cell
turnover, and deterioration of the skin quality both intrinsically and
extrinsically [10,13,16,17]. Collagen
fragmentation is a major histologic feature of aging skin, with significant
fragmentation of the collagen occurring in the extracellular network of the
dermis. This can lead to a loss of dermal thickness in late adulthood,
sometimes up to 20% . Collagen fragmentation
not only weakens the dermis but also causes a decrease in fibroblast activity, with
lower levels collagen synthesis and an increased rate of collagen breakdown by collagen-degrading
enzymes . Accompanying this process Is
usually concomitant lipoatrophy, a disproportionate loss of subcutaneous fat to
overall weight [11,19]. This is especially
evident in the face where subcutaneous fat is partitioned into discrete
compartments that show signs of aging at different rates leading to the typical
facial wrinkles and pronounced nasolabial folds .
It is also this loss of subcutaneous fat on the dorsum of the hands that give
them a wrinkled appearance .
The changes seen in aging skin are very
similar to the effects of HIV-associated lipoatrophy, the result of a
combination of rapid weight loss and side effects of antiviral medications. It
is because of similarities of the physical characteristics of aged skin to HIV-associated
lipoatrophy that some dermatologists have started to use both PLLA and CHA as
off label treatments for aging skin.
Poly-L-Lactic Acid, a member of the
alpha-hydroxy acid family, has historically been used in medical devices as a
component of absorbable sutures and screws [1,16].
It wasn’t until 1999 when injectable PLLA was first introduced as an FDA
approved cosmetic volume enhancer for HIV lipoatrophy of the face and, later,
for cosmetic indications like nasolabial fold deficiencies and wrinkles [1,5]. In contrast to traditional fillers such as
exogenous collagen or silicon injections, deep dermal injections of
microspheres of PLLA stimulates an inflammatory tissue response that leads to
neocollagenesis, gradual dermal fibroplasia and increased dermal thickness [2,4,16,17,20]. The inflammatory response is initiated
by the slow degradation of the PLLA microspheres that are hydrolyzed into
lactic acid monomers by macrophages, mast cells, and lymphocytes. This leads to
an influx of fibroblasts with the deposition of type III collagen that is
eventually replaced by type I collagen fibers .
Because the mechanism of action is based on the stimulation of collagen
production, the effects are not immediate. However, the delayed bio-stimulatory
effect can result in a more favorable outcome with a thicker dermis and improved
skin texture . The results appear to be as effective
as and longer lasting than fat injections at improving contour irregularities [1,4]. Initially, the major risk of PLLA was the potential
for granuloma formation . This risk has been greatly
reduced by increasing the reconstitution volume from 3ml to 5ml with deionized
water and allowing the reconstituted PLLA to sit overnight before use [5,20].
In practice, PLLA is FDA approved
for treating HIV associated lipoatrophy of the face and for facial cosmetic
issues such as wrinkles, skin folds, volume deficiency, and nasolabial fold
contour deficiencies [8,20]. Studies have shown
that PLLA is a reliable and long-lasting treatment for these cosmetic issues
with an associated high patient satisfaction rate .
Some examples of off label use include treatment of acne and varicella scars,
chest wall “step-off” abnormalities following breast reconstruction, prominent
facial asymmetry/Romberg syndrome, soft tissue volume deficiency on the dorsum
of the hands, gluteal enhancement, neck, abdomen, and post-operative soft
tissue loss after melanoma excision [1,7,8].
One of the more interesting uses of
PLLA was seen in a case report by Schulman et al where the authors treated a
“step-off” abnormality between the contour of the right breast implant and
ribcage of a thin 63-year-old woman . After 6
months of failed attempts at surgical correction with acellular cadaveric
dermis, the decision was made to use PLLA to induce production of collagen to
add volume and smooth the deformity . The
patient received 2 vials (367.5 mg each) of PLLA monthly for 4 months that was
injected into the subcutaneous tissue and deep dermal layers. By the final
treatment a significant esthetic improvement had been seen and was not
diminished by her last follow up appointment at 9 months . This shows the potential usefulness that PLLA has
in treating soft tissue deformities as a minimally invasive alternative to
The treatment of acne and varicella
scars is a particular area of interest due to the historic difficulty in treating
these scars. They previously required multiple treatments with several
different modalities before improvement was seen .
However in a case report by Sadick and Palmisano, PLLA was used to treat a 60-
year old white woman with significant acne scars on bilateral cheeks. In this
study, improvement was seen within 24 months in this patient with
moderate-to-severe scarring. Even after just 7 treatments with 4-week intervals,
there was a significant reduction in scar size .
Their results matched the outcomes that were described in an open-label study
that investigated the use of PLLA for acne and varicella facial scars [8,23]. It was also hypothesized that the rapid
improvement in the severity of scars was due to the subcision of the fibrous
bands at the base of the scars by the needle itself that allowed the depressed
scars to elevate, rather than solely the collagen stimulation by the PLLA.
Calcium Hydroxylapatite’s (CHA) mechanism
of action is very similar to PLLA with neocollagenesis and subsequent filling
effect that strengthens the dermis after a deep dermal injection . CHA is composed of inorganic calcium hydroxylapatite
microspheres in a gel solution composed of sterile water, glycerin, and
carboxymethylcellulose [2,3,6,11,17]. CHA
stimulates an inflammatory response much like the PLLA response . CHA injections also share the long-term effects of
dermal remodeling that PLLA has. Punch biopsies taken 4 and 9 months after CHA
injections showed an increase in elastin and collagen 1 and 3 with an increase
in overall thickness, elasticity, and pliability of the skin [10,11,18]. CHA has FDA approval for the treatment of
HIV lipoatrophy and facial volume deficiency, as well as for dorsal hand filling
. Many dermatologists are also using CHA for
These treatments include replenishing
volume loss in the deep fat compartments of the midface and submental area.
Results have been positive with deep injections .
It has been shown to replenish lost volume to the mid and lower face which creates
a smooth and youthful jawline . Other treatments
that have been successful are the filling of periorbital hollows, dark circles,
and lower eye bags and for the treatment of acne scars [22,24].
One advantage of CHA compared to PLLA is that the volume enhancing results
appear more instantaneous because of the gel component of the injection. The bio-stimulatory
effect on collagen deposition can persist for up to 12 months .
Some dermatologists have also begun
using CHA for treating other non-facial volume loss and skin laxity. Diluted superficial
injections of 1:2 and 1:4 with sterile saline have been effective in treating
the neck, upper arms, buttocks, thighs, and abdomen [7,23].
One singled-armed, clinical study of 20 healthy Caucasian woman (ages 28-67)
showed significant improvement in skin flaccidity in these areas after 5 weeks
of treatment . CHA has shown promising
results with high patient satisfaction rates in the upper arm specifically,
with ultrasound showing increased dermal thickness and a decreased skin flaccidity
and improved volume after only 2 treatments in some patients [11,18]. CHA has been used in treating stretch marks,
as well, with a decrease in the appearance of red and white striae when
combined with topical ascorbic acid . There
have also been some studies that have investigated CHA’s effectiveness in
treating cellulite. When combined with MFU-V (micro focused ultrasound with visualizations)
there have been statistically significant improvements in cellulite severity .
Cellulite is a common cosmetic
issue for many people, with estimates of up to 85% of women over the age of 20 affected
by some degree of cellulite [14,26]. Cellulite
is often described as ripples and dimples of skin in the thighs and buttocks. While
often associated with obesity, cellulite is likely a result of underlying
adipose tissue herniating through altered or damaged subcutaneous fibrous
connective tissue [15,27,28]. In addition, many
patients with normal BMIs can present with cellulite of varying severities [27,29]. Multiple factors are hypothesized to
contribute to the development of cellulite including persistent low-grade
inflammation, microvascular dysfunction leading to tissue edema, lymphostasis, localized
adipocyte hypertrophy, collagen denaturation, dermal thinning, tissue laxity, and
altered orientation of fibrous septa connecting the reticular dermis to the
deep fascia [15,25,27,28,30,31]. Differences in
microanatomy may explain why more women than men suffer from cellulite.
In women, the superficial adipose
layer has larger fat-cell chambers than men, which may increase the amount of
fat that can herniate through weakened dermal connective tissue . Differences between men and women in the
orientation of the fibrous septa connecting the deep fascia to the reticular
dermis may also contribute. In men, the septa are oriented in a crisscrossing
fashion, while in women there is a more perpendicular orientation which leads
to localized points of tension and the dimpling characteristic of cellulite. In
various studies, it has been shown that a greater percentage of perpendicular
septa correlates with the severity of cellulite [14,26,27,29,31].
For these reasons, therapies, such as PLLA and CHA, that target the dermis and
subcutaneous tissue may be beneficial as a minimally invasive treatment for
The mainstay of therapy for
cellulite has historically been weight-loss and liposuction. However, neither
have proven to be an effective treatment, with some cases worsening in severity
. Many new non-invasive treatments have been
developed to attempt to target various aspects of cellulite [26,27]. Radiofrequency therapy, for example, causes an
increase in local metabolism due to the heat produced by radiofrequencies in
the subcutaneous fat. A subsequent increase in the microcirculation also enhances
lymphatic drainage and breaks down erythrocyte adhesions . It has resulted in improved body shaping in the
outer and inner thighs, reduction in cellulite, and the induction of new
collagen production, improving the dermal strength and decreasing skin laxity [27,30,32]. Massage therapy has also shown promising
results by encouraging the movement of interstitial fluid and improving
lymphatic drainage. One study demonstrated an enhanced presence of longitudinal
collagen bands in areas where distortion and disruption of adipocytes were
Topical treatments have also gained
popularity in the treatment of cellulite. They often consist of either a monotherapy
or a combination of retinoic acid, methylxanthines, laser therapy, and
carboxytherapy . These treatments effectively
camouflage the rippled appearance of the skin through temporary tightening
effects. Retinoic acid increases collagen production with a longer-term effect
on the skin strength . Retinoic acid
treatments saw major epidermal changes weeks after treatment with increased fibroblasts,
collagen levels, and decreased metalloproteases. When combined with caffeine,
there was a significant decrease in cellulite severity .
Dietary supplementations with collagen peptides have also shown stimulatory
effects in dermal cellular metabolism leading to improved biosynthesis of extracellular
matrix proteins that leads to restored dermal structure . More invasive techniques are used to treat cellulite, as well.
Manual subcision of fibrous bands with needles or blades has shown positive
results in decreasing dimpling in cellulite .
Pulsed 1440-nm laser treatment has also been shown to break down these fibrous bands
and induce an inflammatory response that increases collagen remodeling with
more collagen and elastin production .
These treatments, especially in combination,
help address the lymphatic stasis, remove excess lipids, and break fibrous
bands. In addition, many induce neocollagenisis and strengthen the dermis. We
believe that the treatment of cellulite with either CHA or PLLA will be
successful at decreasing the severity of cellulite in patients. In fact, in
some early studies with PLLA, there was at least a one-grade loss of volume and
cellulite improvement in 80% of cases based on the Global Aesthetic Improvement
Scale . These treatments may also serve as another
form of subcision of fibrous bands while inducing production of new collagen.
This will ideally lead to even longer lasting effects than the current
Another area of interest for the
use of bio-stimulatory injections is as a non-invasive option for buttock
enhancement. Lately, buttock enhancement has become one of the most requested
body enhancements with a 58%  increase in
the number performed in 2013 to 2015. Approximately 20,000 Americans underwent
a buttock enhancement procedure in 2015 [33,34].
Like other areas of the body that have been discussed so far, gluteal ptosis is
due to changes in fat distribution, gravitational force, loss of musculature,
and other factors such as pregnancy and dietary disorders . The mainstay of treatment is surgical
augmentation aimed at improving volume and posterior projection, as well as
improving symmetry. This includes procedures that resect excess tissue such as
liposuction, lipofilling/fat grafting, buttock implants with lipofilling, local
flaps, and polypropylene strip gluteal suspension [33,34].
Other techniques have been increasing in popularity, as well, including local
tissue rearrangement and hyaluronic acid gel injections . Because most of these treatments are fairly invasive, there
are some rare, significant complications that can be associated. For example,
wound dehiscence, implant revision, implant removal, implant palpability,
implant displacement, and capsular contracture have been reported . Even the less invasive procedures, such as fat
grafting, can lead to seromas at the donor sites and fat embolism . As of today, fat grafting is associated with the
lowest rate of complications at 10.5%  and
is very effective at shaping the buttocks and correcting asymmetries and volume
deficiencies . However, there has been an
increasing use of hyaluronic acid injections that have shown to be as effective
and safer for temporary gluteal enhancement .
In some studies, it has been shown to have a positive patient rated improvement
and satisfaction rate in only one to two treatments with results lasting about
24 months with a 400mL injection . Due to
the success that hyaluronic acid injections have in patient satisfaction, as
well as the positive results that have been seen in providing long term filling
effects in other parts of the body, bio-stimulatory injectables may also serve
as a useful tool for non-invasive gluteal enhancement. Being able to provide a
long lasting, non-invasive filling effect that strengthens the dermis, provides
an improvement in elasticity, and decreases skin laxity offers patients a
promising alternative to surgery .
Enhancement in Practice
With the promising results that
have been seen recently in the literature, we have begun using bio-injectables,
specifically CHA, in our own practice for gluteal enhancement with great
results thus far. We have developed a very effective procedure that promotes
good results with minimal discomfort during and after treatment. The first step
in the procedure is to evaluate the grade of cellulite by marking each
cellulite band with a marker as the patient stands and contracts the gluteus
muscles. The depth of penetration of the band determines the grade as mild,
moderate, or severe or the depth as shallow, medium, or deep to determine the aggressiveness
of the treatment. The initial markings and evaluation can be seen in Figure 1 which was taken with arms elevated and folded
to frontal waistline.
The next step is to then scrub the
patient’s buttocks twice with a topical antiseptic followed by anesthetizing
the entry point superior to the trochanteric spot. An 11-inch blade is then
used to create a small slit to introduce an infiltrator. We then use a mosquito
clamp to expand the opening to the subcutaneous tissue. A previously prepared
tumescent fluid (500cc of Ringers Lactate solution plus 1% lidocaine and
1:100,000 epinephrine for a 0.1% lidocaine concentration) is injected in a
fanning fashion using an infiltrator. Once the site is anesthetized, Capistrano
and/or Keil cobra cannulas are used to break the cellulite bands with strong
long strokes in multiple directions. The excess fluid is then drained from the
entry points following successful breakage of the bands. Lastly, we inject 6cc
of CHA that is reconstituted with sterile 6cc of lido without epinephrine into
the upper buttock area in equal parts bilaterally. The buttocks are then
manually massaged, and the entry points are dressed with absorbing material.
As can be seen in Figures 2 and 3, which are taken one week and 6 weeks
after treatment respectively, we have had very positive results with the new
procedure. This procedure offers a less invasive way to treat cellulite that
decreases the discomfort during and after treatment compared with previous
treatments and requires no analgesic therapy.
Since their introduction for the
treatment of HIV-associated lipoatrophy of the face, the use of bio-stimulatory
injectables Poly-L-Latic Acid (Sculptra™)
and Calcium Hydroxylapatite (Radiesse™),
has increased significantly with positive results. They are now used for
treating cosmetic facial aging symptoms such as age-associated lipoatrophy,
wrinkles, and redistribution of soft tissue with positive patient satisfaction
and long-lasting effects. They have demonstrated, due to a foreign body-like
reaction, an increase in the production of collagen that leads to a
strengthening of the dermis as well as a gradual filling effect in treatment
regions. This makes them beneficial in treating acne scars, stretch marks,
dorsal hand aging lipoatrophy, skin laxity in upper extremities and abdomen,
filling in “step-offs” in breast implants, and in treating cellulite. In the
treatment of cellulite and for gluteal enhancement, we believe they have the
potential to provide long lasting results through a less invasive procedure.