Biostimulators are injectable agents whose primary therapeutic action is not mechanical displacement but the induction of a controlled foreign-body response that results in new collagen deposition. Three agent classes dominate clinical use, and each achieves collagenesis through a distinct mechanism.
Poly-L-lactic acid (PLLA)
PLLA is a biodegradable, biocompatible synthetic polymer supplied as a lyophilised powder that is reconstituted and injected as a suspension of microparticles. Once in the dermis, the microparticles provoke a subclinical inflammatory response: macrophages recognise the particles as foreign material and initiate a fibroblastic cascade, ultimately depositing type I and type III collagen around the resorbing particles. The clinical result is delayed by design — visible improvement typically emerges over 4 to 8 weeks and continues to build over several months, which is why PLLA is treated as a series (typically three sessions spaced four to six weeks apart) rather than a single-visit correction.
A key teaching point: PLLA's onset delay is frequently the source of patient dissatisfaction when expectations are not set correctly at consultation. Students should be trained to explicitly manage this timeline in the consent conversation, distinguishing PLLA's mechanism from the immediate volumetric effect of a hyaluronic acid filler.
Calcium hydroxylapatite (CaHA)
CaHA is suspended in a carboxymethylcellulose gel carrier and provides a dual mechanism: immediate volumetric effect from the gel and microsphere bulk, followed by a biostimulatory phase as the microspheres act as a scaffold for fibroblast attachment and collagen synthesis, while the gel carrier is gradually resorbed over roughly 3 to 4 months. This dual action makes CaHA popular for areas needing both immediate contour correction and durability, such as the jawline, chin, and dorsal hands.
Polynucleotides as biostimulatory agents
Polynucleotides, derived from purified DNA fragments (commonly of salmon or trout origin), act through a different pathway: they are thought to stimulate fibroblast proliferation via purinergic receptor signalling and to have documented anti-inflammatory and tissue-hydrating properties, alongside promoting angiogenesis. Unlike PLLA and CaHA, polynucleotides do not rely on a foreign-body/microparticle mechanism, which is part of why they are increasingly used in more delicate or thin-skinned areas such as the periorbital region.
Comparative teaching table
| Agent | Immediate effect | Onset of biostimulation | Typical duration |
|---|---|---|---|
| PLLA | Minimal (diluent resorbs quickly) | 4–8 weeks | 18–24 months |
| CaHA | Immediate, moderate | 6–8 weeks | 12–18 months |
| Polynucleotides | Minimal-to-mild (hydration) | 2–4 weeks | 3–6 months per course |