Introduction

Poly-l-lactic acid (PLLA) is a synthetic polymer derived from lactic acid that is both biocompatible and biodegradable.

The purpose of this chapter is to discuss current techniques used with PLLA to effectively and safely address changes observed with facial aging. Proper patient selection and assessment, as well as attention to technique in the preparation and injection of the material, will minimize adverse events and optimize results.

Product and mechanism of action

The currently commercially available form of PLLA consists of microparticles of PLLA measuring 40–63 µm in diameter. This particle size ensures that the particles are large enough to avoid phagocytosis by dermal macrophages or passage through capillary walls, but small enough to be easily injected by needles as fine as 26 gauge.

The mechanism of action of PLLA begins with a subclinical inflammatory tissue response following implantation, followed by encapsulation and subsequent fibroplasia. This fibroplasia volumizes the tissue and produces the desired cosmetic result.

Poly-L-lactic acid: technical considerations

Methodology is an important determinant of biocompatibility with stimulatory agents. This is outlined below and summarized in Box 7.1.

Box 7.1

Product reconstitution

No less than 5 mL of sterile water, with a hydration time of no less than 2 hours, but preferably overnight (bacteriostatic saline for injection has been substituted for sterile water by some injectors but is ‘off-label’). Add fluid gently and leave to hydrate. Do not shake the vial until it is adequately hydrated to avoid deposition of dry clumps of material on the wall of the vial. Currently, a final dilution of 8–9 mL is the most commonly used. This final dilution can be achieved by adding additional water and/or lidocaine 1–2% with or without epinephrine at the time of hydration or immediately prior to injection.

Product amount

The amount of product used at any single treatment session should be determined solely and completely by the amount of surface area to be treated at that session. The final volumetric correction is addressed by the number of treatment sessions. (The novice injector should be aware that it is initially difficult to resist the temptation to treat to full correction at any one session.)

Product placement

This can be done with a 1 mL or 3 mL syringe and a 25-gauge (long or short) or 26-gauge (short) needle. The depth of placement varies with the location. The product may be placed in the subcutaneous layer in the cheeks, nasolabial folds, and lower face using the cross-hatch or fanning technique (using 0.1–0.2 mL/cm) and may be placed as depot injections supraperiosteally (using 0.2–0.3 mL per injection) along the zygoma, maxilla, and mandible. Deep injections should be avoided around the parotid gland and the masseter. A reflux maneuver should be carried out prior to each injection to avoid inadvertent intravascular injection. This can also be minimized by the use of a 25-guage blunt-tip cannula for injection. Temple injections are placed deeply, under the temporalis muscle. The manufacturer’s instructions are to place 0.05 mL depots in the temple; however, it is common practice among experienced users to place 0.3–0.5 mL depot in this area, followed by vigorous massage.

Product placement precaution

Avoid placement in or through areas of dynamic muscle movement in close proximity to the lips and eyes, which leads to clumping of particles manifesting clinically as lumps and bumps. It may be prudent to inject slowly in a cross-hatch pattern while becoming familiar with the product as PLLA is mixed in water, making for a very low-viscosity solution. Most experienced users prefer the fanning technique (which is more efficient and has the advantage of fewer needle sticks); however, the novice injector must be vigilant to avoid multiple deposits at the apex of the fan.

Aftercare

Massage after every two or three injections and again at the end of the treatment. Have the patient massage over the next few days using the ‘rule of 5s’ (5 minutes/5 times daily/5 days).

Treat; wait; assess – wait a minimum of 4 weeks between treatments.

Additional comments

Prevention and treatment of adverse events

The majority of adverse events are small palpable nodules that stem from suboptimal product reconstitution or placement. Histopathology of nodules shows an overabundance of product with a few foreign-body giant cells, often surrounded by skeletal muscle, as seen in Figure 7.1A. Injection of steroids or antimitotics such as 5-fluorouracil (5-FU) will have little clinical effect on these lesions as the majority of the lesion is product and not host reaction to product. (Camouflage of these papules with hyaluronic acid gel until they resolve spontaneously may offer more gratifying treatment.) Clinically relevant granulomatous reactions have been reported with all currently available commercial injectable devices. True inflammatory granulomas are unpredictable and rare (the reported rate varies between 0.01% and 0.1%). Histopathology of a lesion such as this will show an overabundance of reaction to product with foreign-body giant cells too numerous to count, as seen in Figure 7.1B. As this is a host response, treatment with intralesional steroids or 5-FU (0.1 mL 40 mg/mL Kenalog® (triamcinolone) mixed with 0.9 mL 5-FU 50 mg/ mL – no more than 2 mL at one session) may be helpful; however, fortunately most resolve spontaneously over time.

Figure 7.1 Nodule versus granuloma/low-power histopathology: (A) nodule with an overabundance of product trapped in skeletal muscle; (B) true granuloma showing an overabundance of host reaction to a small amount of product.

Reproduced with permission from Fitzgerald R, Vleggaar D 2011 Facial volume restoration of the aging face with poly-l-lactic acid. Dermatologic Therapy 24:2-27

Patient selection, expectations, and satisfaction

Although our initial experience with PLLA was in the HIV population as well as older cosmetic patients, literature has now been published showing that younger or fuller-faced patients may need less product and fewer sessions, as well as fewer retreatment sessions, than older or very atrophic faces. This is illustrated in the patient cases seen in Figures 7.2–7.5. Treatment of patients needing significant volumization is a gradual, progressive correction carried out through multiple treatment sessions. Patients who are thin, often athletic, with a somewhat skeletal appearance often have the most dramatic improvement. Treatments are usually administered at 1-month intervals (although a longer interval between treatment sessions may be prudent for younger or fuller-faced patients needing less volume). Product placement is briefly outlined in the figure legends. Further detail on this subject may be found elsewhere.

Figure 7.2 A 35-year-old patient 3 months s/p one vial PLLA placed supraperiosteally along the anterior maxilla and mandible as well as in the temporal, deep medial cheek, and submentalis fat compartment. Note the increased anterior projection and convexity of the mid-face as well as the effacement of the early nasojugal fold. Note that the subtle increase in chin height gives the illusion of a longer jawline.

Figure 7.3 A 38-year-old patient 3 months s/p two vials PLLA done in one session. Product was placed supraperiosteally along the supraorbital rim, medial maxilla, pyriform aperature, zygoma, and mandible. Product was also placed in the temporal lateral cheek, deep medial cheek, and submentalis fat compartments. Note the effacement of the early shadowing in the nasojugal fold and pre-jowl sulcus leading to sharper definition of the cheeks and jawline.

Figure 7.4 A 38-year-old patient 6 months s/p PLLA two vials per session, three sessions spaced 1 month apart. Note the improvement in the anterior projection and convexity of the face as well as in skin quality. This athletic patient presented with significant loss of volume in her facial fat and therefore required more sessions than most patients her age.

Figure 7.5 A 59-year-old patient 6 months s/p PLLA three vials per session, two sessions spaced 1 month apart. PLLA was placed supraperiosteally along the supraorbital rim, anterior maxilla, pyriform aperature, and mandible, and in fat compartments in the temple, cheek, and chin. Hyaluronic acid and neuromodulator were placed around the eyes and lips with the initial treatment. Note the ovalization and increased anterior convexity of her face as well as the improvement in skin quality.

The gradual, rather than immediate, results may not make this the optimal choice for someone looking for a ‘quick fix’ for an upcoming event. It is, however, an excellent choice for those wanting long-lasting results. PLLA is the only filler currently on the market that is approved by the US Food and Drug Administration to last up to 25 months and results in high patient satisfaction.

Pathophysiology of the aging face: structural and morphologic

Loss of volume in the bony substructure and fat compartments of the face occurs with age. This is compounded by the loss of elasticity of the skin that envelops it. Change in one area may greatly influence neighboring tissues, leading to a cascade of secondary events. The central role of volume loss and deflation, rather than ptosis, in the aging face has been eloquently illustrated by Lambros. Recognizing where volume is lacking or has been lost in each individual will greatly enhance our ability to address it with site-specific corrections in order to achieve optimal, natural-looking results. Congenital asymmetry in a young patient illustrates some of the clinical effect of the presence or absence of volume in all structural layers and is pictured in Figure 7.6.

Figure 7.6 Congenital asymmetry provides an illustration of the contribution of all structural tissue layers to the morphology of the face. Note how the presence or absence of tissue in all layers results in a more or less clinically obvious tear trough, nasolabial fold, and marionette line/lip lag on the more or less volumized side.

Reproduced with permission from Fitzgerald R, Vleggaar D 2011 Facial volume restoration of the aging face with poly-l-lactic acid. Dermatologic Therapy, Vol. 24, 2011, 2-27

Stuzin has stated that a youthful face represents a point in time when a particular set of skeletal proportions is ideal for their overlying soft tissue envelope. Recent literature does in fact reveal that significant changes do occur in specific regions of the facial skeleton with advancing age, and that these morphologic changes in bony structures affect soft tissue position. Much of this literature has been summarized in an excellent recent review by Sharabi et al. The most significant changes have been documented in the glabellar, orbital, maxillary, and pyriform angles, as well as in the height and width of the orbital aperature and pyriform aperature, and are illustrated in Figure 7.7. This work supports the ‘concertina’ effect concept presented by Pessa over a decade ago stating that deficient bony support may account for soft tissue bundling seen in both infancy and advancing age, i.e. that ideal proportions may be a place we grow into from infancy and away from with age. The clinical value of this work lies in its implications for craniofacial augmentation by solid implants, or by injectable agents, resulting in the restoration of tissue support and a reversal, to some degree, of the ‘concertina’ effect.

Figure 7.7 A pictorial summary of age-related changes to the mid-face skeleton. (Left) Features of a youthful skull include a malar eminence, infraorbital rim, and pyriform aperture that are positioned anterior and vertical in the sagittal plane. The orbital aperture is small with a horizontally positioned inferior orbital rim. (Right) Older patients have a retroclined malar eminence, infraorbital rim, and pyriform aperture compared with that of young patients. The orbital aperture area is increased secondary to progressive curve distortion of the orbital rim superomedially and inferolaterally.

Rohrich & Pessa have performed multiple cadaver studies showing that subcutaneous fat is compartmentalized, specifically by fascial extensions that travel from superficial fascia to dermis (which dictate the location and shape of each compartment). These fascial extensions form a framework that provides a ‘retaining system’ for the human face as well as a conduit for blood vessels and are depicted in Figure 7.8. Superficial compartments are supported by deep fat compartmentalized in a similar fashion. Implicit in this concept is the suggestion that the face ages three-dimensionally, with separate compartments changing relative to one another by both position and volume. Volume loss of specific fat compartments leads to loss of anterior projection (deep fat) and predictable changes in the topography of the face (superficial and deep fat). Understanding the anatomy of all of these areas lends greater precision to our ability to rejuvenate the aging face.

Figure 7.8 An artist’s rendition of the subcutaneous compartments of the face in relation to the perforating vessels from the source arteries (facial, angular, transverse facial, superficial temporal, and zygomatico-orbital arteries).

Conclusion

PLLA is a safe and effective treatment in both younger and older patients. Optimizing outcomes and minimizing adverse events with this product are not difficult but do require awareness of and attention to the technical details outlined above. Careful patient selection will maximize satisfaction for both the patient and physician. Thoughtful facial analysis of changes in all structural tissues will enhance site-specific augmentation of volume loss and enhance outcomes