INTRODUCTION
Poly-L-lactic acid (PLLA) (Figure 1)1 is a synthetic, biocompatible,
biodegradable polymer that has been used
in various medical applications for more than 3 decades.
1,2 For its use in soft tissue augmentation, it is supplied
in a sterile glass vial as lyophilized powder, which includes
nonpyrogenic mannitol, sodium carboxymethylcellulose, and
PLLA microparticles.3 The diameter of the microparticles is
tightly controlled, measuring on average between 40 μm to
63 μm; particle size is key to product performance, as particles
in this range are large enough to avoid both passage through
capillary walls and phagocytosis by dermal macrophages, but
small enough for easy injection.1 Prior to use, reconstitution
of the lyophilized product through the addition of sterile water
forms a hydrocolloid suspension.1,3
Poly-L-lactic acid is a relatable example of the clinical utility
of biocompatible materials. The biocompatibility of a product
pertains to its ability to generate a beneficial cellular or tissue
response in a particular clinical application.4 Implanted polymeric
biomaterial results in an inflammatory response (Figure
2), the nature of which is determined by many factors that can
be broadly classified into 3 categories: the biomaterial’s properties,
the host’s characteristics, and the methodology by which
the biomaterial is introduced into the host.5 Consistency in each
of these 3 parameters leads to a predictable host response and,
in the case of collagen stimulators, to a predictable cosmetic
effect that is completely controlled by the clinician.
The impact of the methodology of biomaterial introduction,
as it relates to PLLA, will be explored in detail in “The History
Behind the Use of Injectable Poly-L-Lactic Acid for Facial and
Nonfacial Volumization: the Positive Impact of Evolving Methodologyâ€
section of this supplement.6
The properties of a biomaterial implant that affect host response
include both physical attributes (shape, size, surface
area) and chemical attributes (pH, charge, hydrophilic vs
hydrophobic), in both its initial and degraded forms.5 The
importance of such properties can be illustrated briefly by
looking at one well-established example, the refinement of
microparticle size during the development of polymethylmethacrylate
(PMMA)-based collagen stimulators. Arteplast®,
the first generation of injectable PMMA, had a broad range
of particle sizes and a high level of particles below 20 μm,
resulting in an unpredictable amount of inflammation and
high incidence of granulomas.7 The second-generation agent,
Artecoll®, had greater uniformity in particle size, and while the
results with this agent were improved, further refinement was
necessary to produce the third-generation product, Artefill®,
the first to meet the United States Food and Drug Administration’s
rigorous quality requirements.7
As this example illustrates, a great deal has been learned over
time regarding how the many characteristics of collagen stimulators
can affect their clinical behavior. With the tight control
over the physical and chemical attributes of injectable PLLA
microparticles, the tissue response with its use follows a controlled
and predictable pattern.8 Although the injection of PLLA
into the subcutaneous or the supraperiosteal plane creates
the appearance of immediate volumization due to mechanical
