PLLA (Poly-L-Lactic Acid)

What is PLLA (Poly-L-Lactic Acid)?

PLLA is a synthetic substance that, once injected into the tissue, stimulates your own collagen production and is broken down by the body over time. It does not work like a filler that gives instant volume; it works as a collagen stimulator (biostimulator) whose effect develops gradually.

Chemically, PLLA is a synthetic polymer that is compatible with the body and biodegradable. For soft-tissue treatments it comes as a freeze-dried (lyophilised) powder containing microparticles whose size and chemical properties are tightly controlled. What comes out of the box is not a ready-to-use gel; before treatment it is mixed with a liquid and turned into a mixture in which the particles are dispersed through the liquid (a suspension).

According to research, PLLA microparticles work in two ways: the polymer is slowly broken down by water (hydrolysis), and fibroblasts, the connective tissue cells that make collagen, are stimulated over a long period. Improvement also builds up gradually over the course of the sessions. PLLA was originally used to restore volume in HIV-associated fat loss; today it is seen more as a scaffold (supporting structure) that stimulates collagen production. You can read about the substance’s use for volume and support in the face on the Liquid Facelift with Collagen Stimulators page, and about its use in areas outside the face on the Collagen Stimulator Treatments page.

RELATEDLiquid Facelift with Collagen Stimulators

SOURCEPMID 24719074PMID 42297014PMID 40580932

From powder to suspension: how is the substance prepared?

PLLA is prepared by reconstituting it with a sterile liquid before treatment, and this preparation is considered one of the steps that affect the result. In the early period, when the substance was first used for HIV-associated facial fat loss, nodules and papules (small lumps that can be felt under the skin) were seen with notable frequency. Later experience helped to establish suitable reconstitution volumes and injection techniques.

The timing of reconstitution is also debated. For one product used on the face, body and scars, reconstitution 72 hours before treatment had been recommended since its approval; in 2021, however, the manufacturer allowed reconstitution immediately before treatment. In a study at two centres based on past records (a retrospective study), 274 sessions in 167 patients treated with immediately reconstituted product were reviewed. One patient developed a nodule 30 days after a facial treatment; the overall pattern of adverse events was similar to that reported with product reconstituted in advance.

A laboratory study found that the way particles clump together in the reconstituted mixture can vary with the product, the liquid used, the preparation method and time. However, the researchers clearly stress that these findings do not set a time window for treatment and do not show that clinical safety is improved. In a randomised trial, in which participants were randomly assigned to groups, the same product was reconstituted at two different volumes and compared on the décolletage, and improvement was reported in both groups.

What this means for you: the reconstitution ratio, the waiting time and the mixing method are technical decisions that vary with the product and the area. You can discuss the clinic’s preparation method with your doctor.

SOURCEPMID 24719074PMID 22926148PMID 39285829PMID 42737053PMID 42235050

How does the collagen response develop, and how quickly?

The effect of PLLA is not volume you see on the day of treatment but a tissue response that develops over time. The substance starts a desired inflammatory response in the tissue at a level that does not cause symptoms (subclinical). Through this response, the microparticles become surrounded by a capsule, your own collagen production is stimulated and connective tissue increases. Over time, PLLA breaks down, the inflammatory response fades and collagen production increases; this is how new volume and structural support gradually appear.

According to research, PLLA also affects immune cells called macrophages: these cells shift from an inflammation-promoting state to a repair-promoting state (M2). During this process, there is a sustained increase in the production of type I and type III collagen and elastin; fibroblasts become active, and the supporting structure between cells is remodelled over a long period.

This response has also been studied by biopsy, that is, by taking a small piece of tissue. In a randomised trial with ten healthy women, participants received either PLLA or, for comparison, saline (placebo) 3 times, 4 weeks apart. At 18 weeks after the last treatment, the PLLA group showed increased tissue remodelling and new blood vessel formation, less elastin breakdown than at the start and improved skin quality measurements. No treatment-related adverse events were reported. However, the study included only ten people, and this should be kept in mind when generalising its results.

In practice, this means that with PLLA the result is not assessed on the day of treatment; the effect develops over time, depending on the collagen response. When, and to what extent, a change can be expected in your case is discussed at your consultation.

RELATEDCalcium Hydroxylapatite (CaHA)

SOURCEPMID 24719074PMID 42211639PMID 40580932PMID 39231078

HIV-associated facial fat loss: the substance’s first medical use

PLLA entered aesthetic medicine to meet a treatment need: facial fat loss (lipoatrophy) in people living with HIV. According to a consensus statement that brings together recommendations for use and reflects the shared view of experts, PLLA was approved for use in Europe in 1999. In the US, it was approved in 2004 for the treatment of HIV-associated facial fat loss, and in 2009 for cosmetic use in people with a healthy immune system.

Four studies from this period recorded significant, long-lasting increases in skin thickness over follow-up periods ranging from 24 to 96 weeks. Patients and researchers reported improvements in facial appearance and quality of life. The only adverse event related to the product itself was small papules under the skin that caused no discomfort.

A randomised trial using objective measurement presents a more measured picture. In this trial, HIV-positive adults with moderate or severe facial fat loss received 4 PLLA treatments, 2 weeks apart. At week 24, total facial soft-tissue volume measured by CT scan had not increased. In the injected tissue layers, however, thickness increased moderately, and patients noticed this change too. At the 48-week follow-up, this moderate increase was reported to have persisted in the injected layers but was not seen in untreated areas.

The experience with HIV-associated fat loss laid the groundwork for the later use of the substance for age-related facial changes. According to researchers, understanding the differences in use between the two patient groups helps in tailoring treatment. The information here only describes the origins of the substance; it is not about HIV treatment or a plan specific to this condition.

SOURCEPMID 24719078PMID 16820069PMID 18193500PMID 19245538PMID 22052268

Uses on the face and in other areas

Today PLLA is used both on the face and on areas outside the face, but the strength of the evidence varies markedly from area to area. For the face, there is a double-blind (neither the patient nor the assessor knew which product was used), randomised trial with 252 participants comparing PLLA with hyaluronic acid for nasolabial folds. In this trial, the rate of effective correction at week 48 was 92.4% in the PLLA group and 59.3% in the hyaluronic acid group; in the early period, however, hyaluronic acid gave better results. According to the researchers, hyaluronic acid gives rapid improvement, whereas PLLA needs more than one session early on; the choice of filler should therefore be tailored to each patient’s priorities.

Outside the face, the backs of the hands, the décolletage, the neck, the buttocks, the inner ankles and acne scars are among the areas where the substance is used; however, published experience in these areas is limited. According to an international consensus statement on body treatments, the evidence here consists largely of prospective observational analyses and case series (reports describing individual patients’ experiences). The available data support a possible benefit for the neck, knees, abdomen, hands and upper arms, but treatment protocols need to be standardised for each area. In a US study that reviewed the records of 498 people from 9 centres, the buttocks were the most commonly treated area; outside the face, larger volumes were generally used than on the face.

Approval history should not be read as a quality badge; the approvals cited in the consensus statement were given for specific intended uses. When the clinic assesses a product, approval by the US Food and Drug Administration (FDA) is not a criterion on its own; the product’s CE marking, its registration and conformity status in Türkiye and the manufacturer’s intended purpose are what the assessment is based on. You can find details of facial treatments on the Liquid Facelift with Collagen Stimulators page, and details of areas outside the face on the Collagen Stimulator Treatments page.

RELATEDCollagen Stimulator Treatments

SOURCEPMID 41694326PMID 22926148PMID 39592491PMID 42004285PMID 24719078

How many sessions? Approaches in studies

In studies, PLLA has mostly been given over more than one session, but no single number of sessions stands out. According to research, PLLA needs staged sessions because improvement builds up over time. Explaining to the patient in detail beforehand that results will appear with a delay is also considered a key part of setting realistic expectations.

Study protocols reflect this variety. In a survey study at a single centre of patients given PLLA for cosmetic purposes, to which 221 people responded, people received an average of 3.3 treatments and reached their greatest improvement over several sessions. In the biopsy study, 3 treatments were given 4 weeks apart; in the randomised trial on the décolletage, up to 4 treatments were given one month apart. In real-world data on areas outside the face, most people (72%) had 2 or 3 sessions; however, only people who had had at least two sessions were included in this study.

A similar caveat is needed about how long the effect lasts. The survey study reported that the improvement lasted up to 24 months. In a review that systematically screened randomised trials of PLLA on the face, some of the studies showed that the effect lasted at least 25 months. However, the evidence in this area is of low quality, and the reported high effectiveness and long-lasting effect need further research.

These protocols describe what was done in studies, not your plan. How many sessions you have, and at what intervals, is decided for you at your consultation; you can ask your doctor about this.

SOURCEPMID 42297014PMID 19207324PMID 39231078PMID 42235050PMID 42004285PMID 39339028

Areas that need extra care

In studies, certain areas stand out as needing particular care with PLLA because of the risk of nodules or serious complications: around the mouth, around the eyes, the temples and the front of the neck. In the survey study of cosmetic PLLA experience, nodules that could be clearly felt and seen were reported in 12 patients; 9 of these occurred around the mouth and 3 around the eyes or at the temple. According to the researchers, the rate of nodules can be reduced by avoiding these areas.

A foreign body granuloma is an inflammatory tissue reaction that the body forms against a foreign substance. A systematic review of granuloma cases linked to collagen stimulators also reported the area around the mouth as a high-risk area. There is a separate warning for the front of the neck: injecting PLLA into this area falls outside the product’s defined intended purpose (off-label) and can lead to a higher rate of nodules.

Choice of area also matters for the risk of vision loss. A review of vision loss cases linked to collagen stimulators reported two confirmed cases of vision loss associated with PLLA; one was linked to an injection around the eyes and nose, the other to an injection into the temple. These cases are rare, but they show why choosing the area is a safety decision.

You can ask your doctor directly, before the procedure, how the clinic approaches treatment in these areas.

SOURCEPMID 19207324PMID 41132036PMID 35960980PMID 41263987

Nodules and papules: why they form and how doctors try to prevent them

Nodules and papules are the main side effect specific to PLLA, and they fall into two separate types. In the first type, papules and nodules usually appear a few weeks after the injection; in most cases they can be felt but cause no symptoms and cannot be seen from the outside, and most of them go away on their own. Because they are largely caused by errors in how the substance is prepared or placed, their rate can be reduced by improving the injection method.

True inflammatory granulomas are a separate condition. They are very rare (0.01%–0.1%) and reflect an excessive reaction of the body to the substance. They can appear months or years later, can persist without going away and can grow. According to research comparing collagen stimulators, nodule formation is most marked with PLLA, and its rate ranges from 4.7% to 28.6% depending on the study. At the 48-week follow-up of the randomised trial in HIV-associated facial fat loss, the rate of nodules under the skin was 10%.

According to a review of 40 studies on PLLA nodules, nodule formation appears to be linked to the reconstitution protocol, injection technique, preparation method and injection depth. Treatment options include monitoring, steroid (cortisone) injections into the nodule, 5-fluorouracil, antibiotics, immunotherapy and surgery. The conclusion the researchers stress is this: effective management starts with prevention.

Massage after treatment was long considered part of preventing nodules. In a randomised trial with 20 people with facial fat loss, one group massaged according to the traditional regimen (5 times a day, for 5 minutes, for 5 days) and the other group did not; the person assessing the results did not know which group had massaged. No nodules were found in any participant, and there was no difference in effectiveness between the two groups. According to the researchers, massage has no meaningful effect when current preparation and injection recommendations are followed. Your doctor will tell you what aftercare the clinic recommends after treatment.

SOURCEPMID 24719076PMID 42211639PMID 19245538PMID 42438624PMID 27618389

Can it be dissolved with hyaluronidase?

No. PLLA cannot be dissolved with the enzyme hyaluronidase. Hyaluronidase is an enzyme that breaks down hyaluronic acid molecules, and it is considered the preferred option for managing complications and unwanted aesthetic results caused by hyaluronic acid fillers. PLLA, however, is not hyaluronic acid; it is a different polymer.

A case series on blood vessel problems caused by non-hyaluronic acid fillers, describing the experiences of a few patients, stated that the lack of an antidote for these fillers makes the situation particularly difficult. In the same series, hyaluronidase was also added to the treatment in one PLLA case, and the condition resolved without tissue death (necrosis) or scarring. However, the researchers assume that this effect came from the release of a narrowing (spasm) in the blood vessel, not from dissolving the filler. This assumption is based on three cases and is not a way of reversing the treatment.

In practice, this means that if you are not happy with a PLLA result, there is no way to reverse it with an enzyme; the substance is only broken down by the body over time. At the clinic, for fillers done elsewhere, the type of filler, when it was injected and where are asked about first; dissolving treatment is not given directly to a filler whose contents are unknown or that cannot be confirmed to be hyaluronic acid. This also matters for people who have had PLLA in the past.

RELATEDFiller Dissolving

SOURCEPMID 41517528PMID 38955457PMID 24719074

Limits of this substance

The aim of PLLA is volume and tissue support; excess skin is not something this substance treats. It has not been shown to reposition sagging tissue in the way surgery does. A review that critically examined studies of hyaluronic acid, calcium hydroxylapatite, poly-L-lactic acid and polycaprolactone highlights an important point: the term “lift”, which is widely used in this field, has no agreed definition, no measurement standard and no validated threshold for what counts as clinically meaningful. All the published numerical measurements also reflect changes at the skin surface. The researchers also note that this does not prove that fillers have no lifting effect at all.

The second limit is the size of the effect. In the randomised trial using objective measurement in HIV-associated facial fat loss, total facial soft-tissue volume had not increased at week 24; the increase was limited to moderate tissue thickening in the injected layers. This finding should be considered together with the improvement that patients noticed; even so, it shows that the measured change can be limited.

The third limit is the evidence itself. In the systematic review that screened randomised trials of PLLA on the face, 11 studies out of 1,467 records met the criteria. Of these, 5 were found to have a high level of methodological weakness that could distort the results (risk of bias), and the evidence was described as low quality. For body treatments, too, the evidence consists largely of observational analyses and case series.

The final limit is that the substance cannot be reversed: PLLA cannot be dissolved with hyaluronidase and is only broken down by the body over time. These limits are not a list of flaws but information you need to know before making a decision; what they mean for your situation is discussed at your consultation.

RELATEDWhy does the face sag?

SOURCEPMID 42620772PMID 18193500PMID 39339028PMID 39592491PMID 24719074

Known risks

A PLLA injection is a medical procedure and has risks. The most common injection-related effects are discomfort, bruising, swelling and redness; these are usually temporary and go away on their own. In the systematic review of randomised trials on the face, all adverse events were mild or moderate; the main ones were bruising, a collection of blood under the skin (haematoma), tenderness, nodules and swelling (oedema).

In real-world data on 498 people treated in areas outside the face, most treatment-related adverse events were linked to the injection and were mild or moderate. The most common event was bruising at the injection site (5.0%), and a nodule was seen in only one person (0.2%). These data come from a retrospective review of past records.

According to the systematic review of foreign body granulomas linked to collagen stimulators, all the collagen stimulators studied can cause this reaction; 30.77% of the reported cases were associated with PLLA. According to the researchers, this reaction is reported more often and appears later with fillers that do not break down (permanent fillers). In the cases in the review, the condition was noticed between one week and fifteen years after treatment, and the symptoms were most often resolved by surgical removal.

The most serious risk is the substance being injected into a blood vessel by accident. The review of vision loss cases linked to collagen stimulators reported two confirmed cases of vision loss associated with PLLA. These cases are rare, but their consequences can be severe.

Blood thinners, antiplatelet medicines (which stop blood platelets from clumping together) and supplements that can affect bleeding are asked about before the procedure. Do not stop any prescribed medicine on your own. If needed, the procedure is planned or postponed after consulting the relevant doctor. How much these risks weigh for you is discussed at your consultation, together with your medical history.

SOURCEPMID 24719076PMID 39339028PMID 42004285PMID 41132036PMID 41263987