Polylactic Acid

Dr Paul Charlson considers whether polylactic acid is the holy grail of anti-ageing

DR PAUL CHARLSON

Dr Paul Charlson FRCGP FBCAM DRCOG DOccMed DPD is an aesthetic doctor working in London and Yorkshire. Dr Charlson is a past president of the British College of Aesthetic Medicine (BCAM) and the co-chair of the Clinical Advisory Group of the Joint College of Cosmetic Practitioners (JCCP) (UK). He is part of the Galderma faculty, which markets Sculptra, and was the lead trainer for Beauty Europe UK..

Polylactic acid is an effective, safe and long-lasting product that produces significant neo-collagen in the extracellular matrix. These products can address a large variety of aesthetic concerns. Currently, four licensed products are available in the UK: Sculptra and Lanluma (poly-l-lactic acid or PLLA), and Lenisna and Juvelook (poly-d-l-lactic or PDLLA acid). There are significant differences between the two enantiomers and each product has distinct characteristics. Despite some negative publicity in the past, these products are safe when used properly, and significant side effects are rare.

DISCUSSION

Natural long-lasting results are the holy grail of anti-ageing and polylactic acid is a product that might be classed as a holy grail treatment. Polylactic acid is a synthetic alpha hydroxy acid polymer, that is biodegradable, biocompatible, and immunologically inert. 1 It causes stimulation of neo-collagenases by triggering a foreign body reaction to the injected material, resulting in a controlled cellular inflammatory response, which activates fibroblasts to produce autologous collagen. 2 This results in a natural and semi-permanent correction of the facial volume loss associated with ageing. Polylactic acid is recommended for increasing skin tightness secondary to ageing. It is effective for reducing the appearance of wrinkles, creases, scars, and other changes caused by ageing and volume loss. It is injected into supraperiosteal, subcutaneous, and subdermal layers to produce optimal results in facial rejuvenation by improving skin quality, firmness, and facial contour. 3

ARE ALL POLYLACTIC ACID PRODUCTS THE SAME?

As mentioned, polylactic acid is available in the UK as injectable products Lanluma and Sculptra (PLLA) and Lenisna and Juvelook (PDLLA). There are some differences between the two substances: PLLA is an irregularly shaped particle 40-65um across and is combined with methylcellulose. PDLLA is a spherical particle with micropores 10-70um across and is combined with hyaluronic acid (HA)⁴ PDLLA has a more significant volumerestoring effect because PDLLA occupies a larger volume than PLLA for the same weight, due to its microporous spherical structure. 5 PDLLA demonstrates superior mechanical stability and biocompatibility compared to poly(d-lactic acid) (PDLA) and PLLA, primarily due to its unique structure. Firstly, it prevents the formation of large crystalline regions typical of PDLA and PLLA. Crystalline regions can render polymers brittle and prone to cracking under stress. In contrast, the lack of crystallinity in PDLLA results in a more uniform and flexible material, enhancing its mechanical stability and reducing susceptibility to mechanical failure.

Secondly, PDLLA degrades in a more controlled and predictable manner compared to the more crystalline PDLA and PLLA. The homogeneous distribution of Dand L-monomers in PDLLA allows for a uniform hydrolytic degradation process. This controlled degradation is crucial in biomedical applications where the timing of polymer breakdown affects the release of therapeutic agents and the healing process.

Thirdly, the amorphous nature of PDLLA also contributes to its better biocompatibility. Crystalline polymers can elicit more significant inflammatory responses due to the presence of sharp crystalline fragments during degradation. In contrast, a more gradual and uniform degradation of PDLLA produces smoother degradation products, less likely to provoke an adverse immune response. Additionally, PDLLA’s degradation products, primarily lactic acid, are naturally metabolised by the body, further enhancing its biocompatibility. 6

Juvelook has a smaller particle size (20-50um) and can be used periocularly and intradermally as a skin booster, which makes it unique. A difference in the volumisation effect of PDLLA compared with PLLA has been observed.7 PDLLA, due to its structure, creates an earlier volume effect which, after several months, stays static. PLLA has a less early effect but catches up with PDLLA over time. Later results, although no comparative studies have been performed, are probably similar. Polylactic acid preparations are not the same and it seems likely that PDLLA may confer some clinical advantages, although as yet this has not been demonstrated by comparative studies.

DOES POLYLACTIC ACID WORK?

Polylactic acid is proven to create collagen and there are numerous studies which demonstrate aesthetic improvements as a result.

There have been high levels of patient satisfaction with the results of PLLA (Sculptra) treatment in both healthy and HIVinfected individuals.8,9

There have been many studies demonstrating the safety and efficacy of PLLA.2,10 Indeed most of the studies have been conducted using Sculptra.

One study showed an increase in type 1 collagen after six and nine months following three sessions at monthly intervals of PLLA.11 A split study on the upper knee demonstrated increased collagen at day 56 after three treatments, lasting at least until day 168.12 Another study showed results of volumisation of sunken cheeks in Asians 24 months after three sessions of treatment with PLLA with a high degree of patient satisfaction.13

Interestingly, in a split face study, there was no difference in collagen production at 12 weeks between one cheek being injected at weeks zero, four and eight and one at four and eight.14

One study found the effect of PDLLA equal to that of HA filler after 24 weeks.15 Another showed significant improvement in dorsum of hands with PDLLA.16 A study using PDLLA showed the biostimulatory effect of increasing elastic and collagen fibres after one week and increasing more later.17

Before

After

One study of Juvelook (PDLLA) showed showed significant improvement with two to three sessions creating increased collagen and elastic fibres with superficial dermal injections.5

It appears that all polylactic acid products have a significant effect on skin rejuvenation usually requiring two to three sessions of treatment. There are more studies relating to Sculptra than Lanluma or the PDLLA products, which is related to its significantly longer existence in the market.

There are no comparative studies of the products, nor consistency of method of administration or treatment protocol. For these reasons, further research is required to develop protocols.

WHAT DILUTION SHOULD I USE?

Currently, there are no papers comparing the dilution of products. However, the dilution recommended for Sculptra is 9ml (8ml water and 1ml lidocaine) and Lenisna (PDLA) 16-20ml (15-19ml water + 1ml-2ml lidocaine). Juvelook, a smaller particle size PDLA, is 8ml (7ml water plus 1ml lidocaine) while Lanluma is 16ml -20ml (15ml water plus 1-4ml lidocaine). Saline may be preferable to dilute PDLLA due to the osmolarity of the product.

More concentrated products (less than 8ml) appear to increase the risk of nodule formation with Sculptra.18

WHAT TECHNIQUES SHOULD BE EMPLOYED?

There have been consensus papers suggesting techniques employed to inject polylactic acids.19,20 There are several considerations. The age of the patient and the amount of volume loss are important. Most treatments with volume products use a cannula. Juvelook is often delivered with a needle or mesogun or with a 27g cannula for the periocular area.

Over-60s

For the over-60s, a multi-layered approach is best to restore bony structure and treat both the deep fat and sub-dermal layers. For heavy faces, it is best to look for areas of volume loss and concentrate on lifting the mid and upper face behind the ligament line.

40s and 50s

The areas to be concentrated on are patient dependant but injection into the temple and malar fat often provides lift and volume with a mixture of products, such as PLLA and HA to rejuvenate the neck and decolletage.

Younger patients

There is less volume loss in these patients. Most injections will be sub-dermal to subcutaneous and will be more targeted to specific areas dictated by patient requirements.

WHAT ARE THE APPLICATIONS OF THESE PRODUCTS?

Facial rejuvenation

Sculptra, Lanluma and Lenisna are all products designed to be used for volumisation of the face by creating a subclinical inflammatory response, leading to collagen deposition in the extracellular matrix, creating a controlled, long-lasting volumisation and reduction of fine wrinkles.21 Juvelook is used mainly as a skin booster and for the periocular area due to its smaller particle size.

Neck and decolletage

These areas are often difficult. In patients with thin skin, it is sometimes useful to treat initially with Juvelook intradermally, then follow up with a more volumising product using a cannula. One study described successful treatment with polylactic acid (PLLA) in the decolletage area.22 Another study also described treatment with good satisfaction in the decolletage area.23

Use of cannulae is likely to lead to less bruising and is favoured. Juvelook can be introduced intradermally with a needle.

Other body areas

These products (Sculptra, Lanluma and Lenisna) can be used for a variety of body areas to create more volume and improved elasticity. The dilution is usually 20ml in most large areas such as the buttocks. A study described treatment using polylactic acid for body contouring.24

Commonly treated areas are buttocks, abdomen, upper arms, knees and hands.

Acne scarring

The treatment of atrophic acne scars using both PLLA and PDLLA is well established.25 Using a needle to inject under the scar is effective, usually two to three sessions at six to eight-week intervals, although there is no consensus on what the best protocol is.

One study described the treatment of atrophic acne scars with a needle-free injection with PDLLA in acne scars with high-level patient satisfaction and this is likely to be the future direction of travel.26

Another study used polylactic acid combined with radiofrequency (RF) microneedling to produce superior results to RF microneedling alone in atrophic acne scars.27

While polylactic acid alone is useful in treating acne scarring, the use of combination treatments is likely to produce optimal results.

Stretch marks

One study described the successful use of PDLLA using laserinduced microjet injection to improve stretch mark appearance. 5 Another described the successful use of PLLA in stretch marks.26

Cellulite Cellulite is characterised by topographic alterations of the surface relief of the skin with depressed areas due to thick subcutaneous septae and raised zones due to the projection of underlying fat to the surface of the skin. This can be treated with subcutaneous injection of polylactic acid.8

IS POLYLACTIC ACID SAFE?

No product is 100% safe, but, with correct techniques and dilutions, unwanted effects can be reduced. In a Brazilian study, complication rates with PLLAs were found to be lower than those for HA fillers with the main issue being nodules. The rate of nodule formation was three times greater in non-physicians compared with physicians. 29 This might suggest that technique is important.

VASCULAR OCCLUSION

This remains a concern with both fillers, calcium hydroxyapatite and polylactic acid. Only HA fillers can be dissolved, which reduces their risk of long-term sequalae. Use by large cannulae and careful slow injection is the best policy. There have been no reports of vascular occlusion with Juvelook due to its small particle size.

NODULES

There are two main types of nodule. Both are rarely seen following injection of polylactic acid.

Granuloma, which is an exaggerated inflammatory response that occurs six to 24 months after injection, tends to grow and cause skin discolouration. Histological conformation is required. 30

True nodules are anomalous accumulations of product due to bad technique or the action of muscles leading to accumulation. They tend to occur one to two months after injection. One study described the techniques to avoid nodules with PLLA, namely massage for several days and deeper injection.31 It is not necessary to massage either Juvelook or Lenisna, although directly after injection, it is sensible to ensure even distribution of product by gentle massage. Another study found no difference in treatment effect or nodule formation in PLLA following massage.32

Treatment of nodules is usually injection with saline and steroids or surgical removal.33 PDLLA has a glass transition (when a substance becomes malleable) temperature of 38-39 degrees Celsius, whereas PLLA it is 60 degrees Celsius. Use of RF microneedling can create a 39 degree environment in the skin, demonstrated resolution of a PDLLA (Lenisna) using an RF device.34

CONCLUSION

Polylactic acid in its various forms is an effective, safe and longlasting product. It produces significant collagen within the extracellular matrix and has multiple uses within aesthetic medicine. It takes eight to 12 weeks to start to produce collagen. Each product on the UK market differs. PLLA in the form of Sculptra has a longer track record of use. PDLLA may confer some advantages being more biocompatible and producing volume earlier. No comparative studies have been performed.

The glass transformation temperature of PDLLA should make nodule resolution easier. There is no consensus as to the volume of diluent required but 16-20ml may be optimum. Proper reconstitution of the product and correct technique and placement will help to reduce nodule formation.

Juvelook is a product unique in the UK. Being a smaller particle, it can used intradermally and periocularly and has no reported nodules.