A new option for volumetric restoration_ poly-L-lactic acid

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JEADV ISSN 1468-3083

ORIGINAL ARTICLE

Blackwell Publishing Ltd

A new option for volumetric restoration: poly-L-lactic acid D Thioly-Bensoussan* St Louis Hospital, Paris, France

Keywords autologous fat, facial volume, poly-L-lactic acid, polymethylmethacrylate, volume restoration *Corresponding author, tel. +33 1 5375 1200; fax +33 1 5375 1500; E-mail [email protected]

Abstract Objectives The market for products and techniques that correct the visible signs of facial ageing is now huge. There is a diversity of devices and treatments now vying for a share of this growing marketplace, including polymer implants and injectable preparations that are based on an array of substances. The vast majority of these devices can only provide temporary correction of superficial lines and wrinkles, with volumetric augmentation being beyond their capabilities. The products and procedures suitable for the restoration of facial volume are discussed here. Results The restoration of facial volume has long been neglected in cosmetic rejuvenation as surgical procedures increase skin tension but do nothing to restore the underlying facial volume, which is a subtle yet important characteristic of the youthful face. Fortunately, devices are now available which can augment facial volume for long periods of time or even permanently. These include implants based on expanded polytetrafluoroethylene and silicone rubber, which provide permanent restoration of volume, but require invasive surgery and do not age with the surrounding tissues eventually resulting in an unnatural appearance. The cosmetic rejuvenation market now abounds with various injectable devices, including: poly-L-lactic acid (PLLA), polymethylmethacrylate, collagens, hyaluronic acids, silicone and calcium hydroxylapatite. The choice of which one to use in practice is physician led, based on facial assessments, product characteristics and the desires of the patient. Conclusion Although there is a wealth of products available, injectable PLLA (Sculptra®) can restore volume to the face providing a natural look. Not only are the results of volume augmentation using this device long lasting, but they are also safe.

Every cell in the human body is subject to the effects of ageing and nowhere is this more evident than the skin of the face. There are many changes that occur in the skin due to senescence. The turnover of cells in the skin is rapid, but this slows slightly with age and the rate at which dead cells are shed also decreases.1 These processes usually begin around the age of 20, but their visible manifestations can take decades to develop and are a result of interplay between the skin itself and the other tissues of the face, including the muscle, bone and fat.1 12

There are many obvious, visible manifestations of ageing, including a loss of translucency that develops due to a reduction in moisture levels and a reduction in the rate at which dead skin cells are sloughed. As cell turnover slows, the skin looks increasingly dull and rough, and chronic dilatation of groups of capillaries causes elevated dark red blotches on the skin (telangiectasia). As the skin becomes less elastic and increasingly dry, fine lines and wrinkles appear. These changes are exacerbated by the activity of the underlying muscles.2 The formation of fine lines and wrinkles is the initial step in the process that

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eventually results in grooves and furrows, the likes of which are found in the nasolabial, glabellar and brow regions. Inelasticity and gravity work in concert to drag the tissues of the face downward. Obvious signs of this tissue ptosis are the heavy jowls of the aged face. This procession is not only felt by the skin, but also by the underlying tissues. Age-associated atrophy affects all of the tissues of the face. Not only do the fat deposits and muscles atrophy, but the supporting scaffold of the facial skeleton also undergoes degeneration and the teeth begin to shrink.3 The deterioration of this framework exacerbates the inelasticity and ptosis of the skin. The additive effect of this atrophy on the skin is most noticeable in the mid-face, the chin and the temples. Although ageing is a ceaseless process, modern cosmetic rejuvenation offers a host of techniques and devices that can be used to reverse the visible effects of facial ageing. Cosmetic therapy can be divided into surgical and nonsurgical means. The skills and experience of the physician are important in the identification of an appropriate treatment strategy, as is an assessment of the patient’s face, in order to determine which areas should be targeted and how. As the visible signs of ageing are varied, the ways in which they should be addressed are correspondingly diverse. Epidermal lesions and variations in pigmentation are most effectively treated with chemical peels and lasers. These techniques are only appropriate for correcting agerelated deficiencies in the most superficial layers of the skin as they rely on the removal of all the layers of the epidermis.4 Wrinkles are more deep-seated than epidermal deterioration and there are a number of ways in which they can be attenuated. Wrinkles can be corrected with an array of what are commonly known as ‘fillers’.5 Fillers are devices based on a range of naturally derived and synthetic polymers and include the collagens and hyaluronic acids.6,7 Fine lines around the mouth and eyes can also be addressed with botulinum toxin (Botox), which actually acts upon one of the causes of these fine lines, the underlying muscles.8 Relatively recently a new class of injectable compounds have been shown to be efficacious in the correction of deep lines, grooves and furrows. Injectable poly-L-lactic acid (PLLA) is one of these devices and has been shown to restore volume to these deficiencies.9–11 Lines and wrinkles of moderate severity can also be addressed with medium and deep chemical peels,12 although the cosmetic result would not be as effective as correcting the wrinkle or fold with a filler or volume enhancer. To correct volume loss, skin density and skin firmness, physicians have a range of tools at their disposal. Density and firmness can be addressed with the use of intense pulsed light lasers and rejuvenation lasers, which act on the collagen within the dermis, tightening it.4 With volume

Volumetric restoration: poly-L-lactic acid

deficits developing in the upper and mid-face, the most effective course of action is to use a volume enhancer, such as autologous fat and polymers like PLLA. When the manifestation of ageing under scrutiny is ptosis/volume redistribution then surgery is an option, which involves tightening the skin using a number of procedures based around the concept of the ‘facelift’.13 Modern treatments, such as injectable volume enhancers, provide results analogous to surgical procedures, but are minimally invasive and involve little or no ‘downtime’. Epidermal lesions and variations in pigmentation, wrinkles, folds, furrows and ptosis have long been targeted by physicians involved in cosmetic rejuvenation. However, depressions and concavities resulting from the loss of subcutaneous fat and contributed to by the atrophy of muscle and bone have only recently begun to garner attention in the world of cosmetic rejuvenation.

Fillers vs. sculptors The armentarium of injectable devices for cosmetic applications is divided into two broad types – fillers and sculptors – the latter being relatively recent additions to the injectables market. Fillers are injectable devices that are only intended for the correction of lines and wrinkles, the likes of which appear around the eyes and lips. Fillers are normally of minimal viscosity and are usually introduced into the upper layers of the dermis directly filling the most superficial deficits. For the deeper lines or furrows we may inject more concentrated and thicker implants. Typical fillers are the very widely used collagens and hyaluronic acids. Sculptors should not be used in the same way as fillers as they are intended for different applications. Sculptors are not intended for the correction of superficial manifestations of ageing. Injectable devices are injected into the deep dermis or upper subcutaneous tissue. They are either non-resorbable or elicit a thickening of the dermis. Identifying which of these treatments is the most suitable for a patient depends on the skills and experience of the physician, the extent and degree of facial volume deficits, product characteristics, and the desires of the patient.

Treatment options for volumetric restoration Numerous potential options exist for the restoration of facial volume, most of which are synthetic polymers, although autologous fat is used for this application (Table 1). Autologous fat is harvested from a region of the body that has substantial deposits of subcutaneous fat (i.e. the buttocks or waist) and it is then transplanted to volume-deficient areas on the face.14 Autologous fat

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14

Permanent ∼1.5 years PMMA, polymethylmethacrylate; PLLA, poly-L-lactic acid; ePTFE, expanded polytetrafluoroethylene.

< 1 years Durability (of results)

1–2 years

< 1 years

> 3 years

2–3 years

Infections, tissue irritation Limited clinical data for cosmetic indication Papules Infection, foreign body reactions Immunosensitivity Safety

Necrosis, inflammation

Immunosensitivity

Requires surgery, commonly used in lips Can cause ‘lumps’ Gradual effect Not resorbed Allergy testing required Additional considerations

Patient must have sufficient fat deposits

Allergy testing required

Large volume deficits Lines, volume deficits Deep lines, grooves, volume deficits Lines, grooves, volume deficits Fine lines Deep lines, grooves, volume deficits Potential treatment targets

Collagens

Fine lines (primarily)

Thioly-Bensoussan

Autologous fat

Table 1 Treatment options for volumetric restoration

Hyaluronic acids

PMMA

PLLA

Calcium hydroxylapatite

ePTFE implants

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provides augmentation of severe facial volume deficits; however, it is carried out during several treatment sessions spread over a long period of time. It is also a surgical procedure with considerable downtime and risks for the patient, and requires the careful removal of the fat tissue to avoid damage, cleansing, preparation and separation.15 Injecting this harvested fat also carries risks as the occlusion of the vascular system is a possibility, which can cause local necrosis, arterial obstruction and ocular fat embolisms.16 Another surgical option for volumetric restoration is the use of expanded polytetrafluoroethylene implants that are tailored to the concavity or depression to be corrected.17 Implants provide an instant effect; however, they too are associated with significant downtime for the patient.17 Another constraint on the use of implants is that they require exact fitting to the concavity in question, failure to do so may lead to the irritation of the tissues by the edge of the implant. Implants can also lead to an unnatural appearance as the skin ages and sags, but the implants remain in their original positions. Various synthetic polymers are available for the correction of facial volume loss. These include devices based on PLLA, polymethylmethacrylate, polyacrylamide, poly-alkyl-imide, polymethylsiloxane and silicone oils.18,19 These polymers provide long-term to permanent correction of facial deficits. All are injected into the skin and mechanically ‘bulk’ the skin out. Poly-L-lactic acid is an exception to this as it provokes a foreign body reaction. Silicone oils were thought to be the perfect substance for facial cosmetic procedures in the early 1960s; however, the manifestation of severe systemic reactions led to their widespread abandonment.20 Recently there has been renewed interest in the injection of silicone oil for the correction of facial fat loss in HIV patients.21 The safety of these new highly purified formulations has yet to be demonstrated in the long term. The only inorganic device to be used in cosmetic rejuvenation is calcium hydroxylapatite, which is a natural component of teeth and bones. It too has been tested in patients with HIV-associated lipoatrophy where it has demonstrated favourable results, filling the large concavities that develop as a result of this condition.22,23 Again, further work is needed to elucidate the durability of these results and their long-term safety.

Poly-L-lactic acid Injectable PLLA is a new type of sculptor, as it gradually thickens the dermis to restore volume. This device has been used in a variety of medical applications for over three decades and has demonstrated excellent safety and biocompatibility.24 It was introduced into the European

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Union (as New-Fill™) in 1999 to increase the volume of depressed areas, such as skin creases, wrinkles, folds and scars. This indication was extended to include large volume corrections of lipoatrophy in 2004. Injectable PLLA (as Sculptra®) received its US FDA approval in August 2004 for the restoration and/or correction of the signs of facial lipoatrophy in people with HIV. The exact mechanism by which PLLA particles stimulate fibroblasts to produce collagen is unknown, but this new collagen creates volume as the PLLA is resorbed and degrades, eventually being respired as CO2.25 Histologically, PLLA injections are accompanied by the proliferation of giant cells and histiocytes.25 Following resorption, a significant increase can be seen in the number of collagen fibres present in the treated area.26

Poly-L-lactic acid: clinical usage Injectable PLLA can restore the facial volume lost with age. The restoration of this volume is accompanied by the rejuvenation of the facial contours. All regions of the face can be treated with PLLA. The upper face (temple hollows, tear troughs and periorbitals) can be treated with PLLA, although it should be injected with caution into the area around the eyes. In the mid-face, PLLA can be used to correct cheek furrows, nasolabial folds and cheek depressions. Poly-L-lactic acid can be injected into the lower face to correct sagging jowls and marionette lines, restoring an oval shape to the face.

Injectable poly-L-lactic acid: volume duration and safety Poly-L-lactic acid is unique among sculptors as it gradually restores the volume lost as a result of ageing. Its novel mode of action can also remodel the shape of the face. The results provided by PLLA are long lasting and safe, supported by the large numbers of patients that have been treated in the EU.9,26 The use of injectable PLLA can also be tailored to each patient making it one of the most flexible treatment options for volumetric restoration.

Future direction Volume loss can be corrected by a range of sculpting devices, all of which vary in the degree and durability of augmentation they provide. The choice of a treatment option depends on the degree and extent of volume loss, physician experience and cost.

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