INTRODUCTION
Poly-L-lactic acid (PLLA) has been used in a variety of medical
applications, such as absorbable sutures, fixation
devices in orthopedic and plastic surgery, and vectors
for sustained release of bioactive compounds for more than 30
years, during which time it has demonstrated excellent safety
and biocompatibility.1-5
Poly-L-lactic acid was first approved for soft tissue augmentation
in Europe in 1999, for the cosmetic correction of scars and
wrinkles.3 The initial recommendations for its use, including
those related to product reconstitution and hydration, injection
sites, techniques, timing, and patient selection, were, in
retrospect, inadequate or suboptimal.6,7 As a result, the full
potential of PLLA was not immediately realized; instead, its
clinical use was associated with a high rate of specific adverse
events (AEs), such as nodules and papules.6-8 Although usually
remaining nonbothersome, nonvisible, and small, nodules can
sometimes necessitate additional interventions, such as surgical
excision.9,10 The early experience with PLLA caused clinicians
to become disenchanted regarding its clinical utility, with many
specialists remaining wary and/or skeptical to this day.6
Over the past decade of clinical experience with the use of PLLA
in soft tissue augmentation, much insight has been garnered
regarding the specific shortcomings of those initial approaches.
Evolution of specific aspects of PLLA methodology by clinicians
and investigators has helped to decrease the frequency of AEs
and improve the cosmetic benefits associated with its use.9,11-25
Taking a specific, historical look at the evolving methodology
of PLLA injection can inform current practice with the use of
this agent, as the accumulated experience provides a requisite
dataset for the establishment of new recommendations.
Upon the initial European approval of PLLA for soft tissue augmentation,
a reconstitution in ≤3 mL of sterile water 3 minutes
prior to injection was recommended.3,6 In clinical use, PLLA
was often injected superficially (as with a dermal filler), at high
concentrations, and with short intervals between treatments.6
In addition, injection sites were often chosen with less discrimination
than was warranted, including facial areas where
there was a risk of the material coalescing, such as the hypermobile
perioral and periocular regions.6,7 Early studies with
PLLA reflected the shortcomings of these practices, which
were associated with a high incidence of PLLA injection-site
subcutaneous papules (Table 1).3,11,18,26-32
In 2004, the European indication for PLLA was extended to include
large volume corrections of lipoatrophy. Coincident with this labeling
expansion, modifications to the methodology of PLLA
reconstitution and injection were largely adopted. Reconstitution
volume was increased to 5 mL, hydration times were increased
from minutes to hours (and eventually to overnight), the interval
between injections was increased to 4 to 6 weeks, postinjection
massage was introduced into the regimen, and clinicians began
to avoid the injection of PLLA into the dermis.9,14,16,19,22,23,30,31,33-36
Although it is impossible to determine which of these methodological
changes had the greatest impact, a significant decrease
