Collagen-stimulating injections (PLLA, CaHA): how they work and the evidence

What are collagen biostimulators?

Injectable materials used in the face include hyaluronic acid, polycaprolactone, calcium hydroxylapatite (CaHA), and poly-L-lactic acid (PLLA), and they differ greatly in how long they last and how they work ^[2]. Among these, PLLA and CaHA are classified as collagen biostimulators and are used to improve skin quality and restore volume ^[1].

A 2025 literature review summarized that hyaluronic acid creates volume immediately but needs to be cross-linked to last a long time, while polycaprolactone and PLLA produce a longer-lasting effect by stimulating collagen production ^[2]. In other words, the difference is between a material that takes up space where it is injected and one that prompts the body to make collagen on its own.

How does PLLA work?

PLLA is a biocompatible synthetic polymer that breaks down in the body ^[3]. The size and chemical properties of PLLA microparticles play a key role in triggering an inflammatory reaction at an unnoticeable level, which stimulates collagen to build up in the matrix outside the cells ^[3].

This literature review explained that the facial volume restored in this way appears in a controlled manner and lasts a long time ^[3]. At the same time, it emphasized that because of the unique properties of PLLA, a dedicated technique suited to it is needed to achieve good results ^[3].

Studies on effects and how long they last

A 2026 systematic review analyzed 14 studies and reported that both PLLA and CaHA produced meaningful improvement in skin elasticity, wrinkle reduction, and facial volume ^[1]. The effect lasted up to 25 months for PLLA and 12 to 18 months for CaHA ^[1].

A 2024 systematic review that looked only at PLLA selected and analyzed 11 randomized controlled trials from 1,467 publications ^[4]. Four of them showed an increase in dermal thickness and improvement in facial fat loss (lipoatrophy) and aesthetic scores, and the effect lasted at least 25 months ^[4]. However, 5 of the 11 studies had a high risk of bias, and the researchers concluded that the quality of the evidence on effectiveness and safety for facial rejuvenation was low and that further validation is needed ^[4].

Evidence for areas other than the face

One PLLA product has been approved for facial aesthetic use in Europe since 1999 and in the United States since 2009, and it has recently also been evaluated in body areas, such as for cellulite on the buttocks and thighs ^[5]. A 2025 international expert consensus statement considered that there are potential benefits for the neck, knees, abdomen, hands, and upper arms ^[5].

However, the evidence for body areas consists mainly of prospective observational studies and case reports ^[5]. The same consensus statement stated that injection techniques for each area need to be standardized and that the tools for assessing results need to be validated ^[5].

Side effects and risks

In the PLLA systematic review, all adverse reactions were mild or moderate, mainly bruising, hematoma (a collection of blood), tenderness when pressed, nodules (small lumps), and swelling ^[4]. In a literature review covering both PLLA and CaHA as well, the most common side effects were pain and swelling at the injection site, but 1 case of compression necrosis (tissue death caused by pressure) with CaHA was reported as a serious case ^[1].

A 2025 literature review summarized that injectable materials in general can cause problems ranging from mild swelling and pain to serious complications such as vascular occlusion (blockage of a blood vessel), nodules, and blindness ^[2]. Reducing risks such as tissue necrosis and vision loss requires a deep understanding of facial anatomy, especially the vascular danger zones ^[2].

• Bruising, hematoma, and swelling
• Pain at the injection site
• Nodules
• In rare cases, serious complications such as compression necrosis and vascular occlusion

What to check during your consultation

The 2026 systematic review considered both ingredients to be effective and safe for facial rejuvenation, but concluded that more research is needed to standardize techniques and assess long-term safety ^[1]. How much collagen is produced can vary from person to person, so it is a good idea to have the change you want and your skin condition assessed through an examination before deciding on the ingredient and treatment plan.

• The ingredient to be used and the level of evidence behind it
• How results appear and how long they are expected to last
• The injection areas and the treatment technique
• What will be done if nodules or vascular complications occur
• Your history of previous filler or other injectable treatments