Biostimulators, PRP to Sculptra.

PLLA microspheres in a reconstituted suspension, injected deep and massaged, provoke collagen around each particle and are gone themselves within about two years. The evidence is in Part 01: the human-collagen comparison (Narins 2010; Brandt 2011), the cheek-wrinkle trial (Fabi 2024), the temple trial (Chang 2026), Gana V's non-inferiority to Sculptra (Han 2023), and the origin story in HIV facial wasting (Moyle 2004). The systematic review of eleven studies found effects "sustained for at least 25 months", superiority over collagen in two, and five of the eleven at high risk of bias, concluding that the evidence "is of low quality" and the claims "should be further investigated" (Signori 2024).

Graded strong on the randomised, controlled, long-follow-up trials that no other biostimulator can match; the caveats are that they are manufacturer-run and that the nodule question is real (Safety). Modern reconstitution — more diluent, longer hydration, deeper placement, avoiding the lips and lower eyelids — cut the nodule rates of the early years, and a 2025 prospective series of 52 women on a newer PLLA brand recorded one small self-resolving nodule (Bravo 2025). Not for the lips, the tear trough or anywhere you want a shape tomorrow.

CaHA microspheres in a carboxymethylcellulose gel give immediate volume from the gel and a collagen response around the particles as it resorbs. The fold evidence: 40% of nasolabial folds still improved at 30 months and no delayed adverse events in 102 patients followed three years (Bass 2010); a CaHA gel non-inferior to Restylane in a 188-subject double-blind trial (Pan 2025). The hand evidence: the twelve-month randomised trial (Goldman 2018). The mechanism: the split-face biopsy study showing type III then type I collagen, elastin and new vessels (Yutskovskaya 2014). The face systematic review rates it "safe and effective" for cheeks, jawline, lipoatrophy and folds, with marionette lines, chin and pre-jowl "also tending to respond" (Guida 2024); a jawline consensus protocol exists (Dallara 2014).

Strong for what it is licensed for. The dilution use is graded in Part 01 (neck and chest moderate; laxity and body emerging), and the safety difference from HA is the one to weigh: an intra-arterial CaHA injection cannot be reversed with hyaluronidase, and the expert consensus on managing it exists because it happens (van Loghem 2020). Gene-expression work found CaHA's signature more inflammatory than PLLA's (Waibel 2025) — a Galderma-funded comparison of a Merz product, to be read as such.

PCL microspheres in a gel carrier resorb over two to four years depending on the product version, which makes Ellansé the longest-lasting biostimulator and the one with the least margin for error. The randomised controlled trial in Chinese patients reported an effectiveness rate of 88.8% versus 23.8% at twelve months, improvement that was sustained while the control group's "gradually vanished" from three months, and injection-related adverse events in 8.8% versus 11.3% (Zhao 2023). The European prospective study found 84% with at least a one-point fold improvement at month 12, 64% at month 18, Global Aesthetic Improvement in over 90% through month 12, and no severe or unexpected events with safety confirmed to 30 months (Moers-Carpi 2021). Head-to-head, PCL reduced fold severity significantly more than PLLA at 3, 6 and 12 months with higher satisfaction and comparable safety (Hu 2025).

Moderate rather than strong because the randomised evidence is one trial plus product-versus-product comparisons, without the decades of follow-up PLLA and CaHA have, and because its longevity is exactly what makes a misplaced or overfilled result a two-year problem. An experienced injector's product, in the cheek and jawline, not a first biostimulator.

These are the products behind the word "booster". Restylane's non-animal stabilised HA was the first: micropuncture injections improved skin quality on the treated side in over 80% of subjects on face, hand and chest (Streker 2013) and increased firmness and viscoelastic recovery in a pilot (Reuther 2010). Belotero Revive (HA with glycerol) improved firmness, fatigue and density in a randomised study (Kleine-Börger 2022) and cut pore volume in a split-face trial (Rutnumnoi 2025). Profhilo's hybrid cooperative complexes of high- and low-molecular-weight HA have laboratory data on fibroblast and adipocyte vitality and clinical reports of reduced wrinkle severity, roughness and laxity with hydration "lasting up to 6 months" (Tintor 2025); the 2026 systematic review of Profhilo and Profhilo Body reports improvements in elasticity, hydration, density and laxity across face, neck, arms, abdomen and hands, with mild events resolving within 72 hours — and manufacturer scientists among its authors (Sparavigna 2026).

What keeps this at moderate is Part 01's sham-controlled trial (Jones 2018) and the funding pattern; what earns it moderate rather than emerging is the consistency and the safety. Post-marketing surveillance of Profhilo projected 1,091,956 exposed patients and 371 adverse events — 0.034%, mostly swelling, redness and discomfort (Salti 2025); the earlier three-year report logged twelve, none serious (Cassuto 2020). Vitamin-and-amino-acid "mesotherapy cocktails" belong here too: the systematic review found HA alone did more than HA with cocktails (Ghatge 2023). If you want a biostimulator with no lasting foreign body and almost no risk, this is it; if you want a result at a year, it is not.

PRP is drawn from your arm, centrifuged to concentrate platelets in a small volume of plasma, and injected or needled back in; platelet granules release the growth factors (PDGF, TGF-β, VEGF, EGF) that plausibly drive fibroblasts, vessels and hair follicles. The indication-by-indication evidence is in Part 01: hair (moderate), scars with microneedling (moderate), facial skin (moderate on thickness, weaker on wrinkles), under-eyes (emerging). What unites them is the variable: a systematic review of 75 randomised trials in 5,726 patients found "significant variability in PRP preparation methods and application techniques, including differences in centrifugation protocols and platelet concentration levels", proposed a quality-reporting score, and found a strong correlation (r = 0.79) between temperature control during preparation and efficacy (Rahman 2024); in the orthopaedic literature only 10% of 105 studies described a reproducible protocol and 16% quantified what they injected (Chahla 2017).

So "PRP works" always means that PRP, at that dose, on that schedule. The narrative review of platelet concentrates in aesthetics concludes the field is "promising yet relatively recent", with small samples and no standardised assessment (Davies 2025). Moderate, on the meta-analyses; the cheapest regenerative option and the only one that is literally yours.

PRF differs from PRP in the spin (slower, shorter) and the tube (no anticoagulant), so the sample clots into a fibrin scaffold that holds platelets and leukocytes and releases growth factors over days rather than at once; injectable PRF (i-PRF) is the liquid version drawn before it sets. The review of platelet concentrates notes that "only few studies have compared PRP versus PRF with all demonstrating superior outcomes using PRF" — and that the studies are small and unstandardised (Davies 2025). The facial systematic review pooled PRP and PRF and identified skin thickness and elasticity as the parameters with the strongest evidence (Qin 2025); the periorbital review found PRF's texture and fine-line improvements fading by six months (Sollitto 2025); a 2024 systematic review of injectable PRF in alopecia and facial rejuvenation is on the same small base (Mohale 2024).

Emerging: plausible advantage, no demonstrated superiority on outcomes that matter, and the same hygiene and dose questions as PRP. Choose the clinic that answers questions about preparation over the one selling the newer acronym.

Polynucleotides are long DNA chains purified from salmon (or trout) sperm, injected into the dermis on the theory that they supply nucleotides to stressed cells, bind water and calm inflammation. The systematic review found "nine studies, of low and moderate quality", 219 patients, "a variation regarding procedural characteristics", promising results on wrinkles, texture and elasticity, "limited consensus regarding their optimal use", and a need for "rigorous, high-quality studies" (Lampridou 2025). The foundational phase 3 trial — randomised, double-blind, matched-pairs, three injections two weeks apart — compared Rejuran with an HA filler on crow's feet: "the primary and secondary objective efficacy outcome measure showed no statistical significance between the two groups" (Pak 2014). The periocular split-face trial against HA likewise found no difference on the visual and global scales, with better instrument scores for elasticity, hydration, roughness and pores on the polynucleotide side (Lee 2022). An exploratory 20-woman study found polynucleotides improving nasolabial skin texture and prolonging a later HA filler (Araco 2023); an open-label Asian series reported benefits persisting to six months (Lim 2024).

Read those trials as they are: the product equalled a hyaluronic-acid filler on wrinkles rather than beating it, and it has never been tested against saline. The regulatory route is the device route, which asks for safety and performance, not efficacy. Emerging: real short-term skin-quality signals, heavy manufacturer gravity, fashionable prices — and a wholly reasonable choice for the person who understands that, and wants a booster that is not HA.

Nanofat is the legitimate end of the "stem cell" spectrum. Fat is harvested, mechanically emulsified and filtered; the resulting fluid contains no viable adipocytes but "adipose-derived stem cells were still richly present", with proliferation and differentiation capacity intact, and the clinical series reported "remarkable improvements in skin quality 6 months postoperatively" with no infections, cysts or granulomas (Tonnard 2013). Its face-focused review lists fine lines, sun damage, scars and even alopecia as uses and concludes that "further studies are needed to assess the long-term efficacy and safety of this technique" (La Padula 2023). Structural fat grafting for volume — a different procedure — sits in the volume loss guide.

Emerging because the evidence is surgeons' series without controls, and because the product is made in the operating theatre from your own tissue, which puts it outside product regulation and inside surgical judgement. It is not what a clinic means by a "stem-cell facial" (next row); it is a plastic surgeon's adjunct, usually added to a lift or a fat transfer rather than sold on its own.

Exosomes are extracellular vesicles that carry proteins and RNA between cells, and the idea of harvesting them from cultured stem cells to deliver a "regenerative signal" without the cells is scientifically serious. The clinical record is not yet: the systematic review of microneedling with exosomes found eight eligible studies with sample sizes "from 3 to 60 participants" and concluded that "more evidence is required before we can ascertain the safety profile and efficacy profile" (Dhaliwal 2026); a 2026 review of skin-rejuvenation studies pooled 21 articles across adipose-cell, platelet, plant and milk sources (Alzahrani 2026); the aesthetic review calls the evidence "early" and flags "the lack of standardization in the production and application" (Shah 2025). The one controlled trial worth reading is an investigator-blinded split-face non-inferiority comparison in which adipose-stem-cell exosomes and PRP "equally improved wrinkling, dyschromia, erythema, texture, and overall skin appearance" with collagen I and glycosaminoglycans up in both arms on biopsy (Estupiñan 2025) — equal to a treatment graded moderate, in one study, with no untreated side. For hair, a systematic review found density gains of 9.5 to 35 hairs/cm² across heterogeneous small studies, the best of them randomised (Al Ameer 2025).

Why limited rather than emerging: the product. No exosome preparation holds a marketing authorisation in the US, EU or UK; the FDA's safety notification followed serious harm from unapproved injections; and the trial exosomes were characterised in a laboratory, whereas the vial dripped on after microneedling in Europe is a cosmetic of undisclosed content and origin — the review of the whole regenerative field says it "lacks the necessary scientific rigour and regulatory compliance" (Rahman 2025). The science may arrive; the €400 add-on is ahead of it. Skip.

The New England Journal of Medicine case series is the reference: three patients received intravitreal injections of autologous adipose "stem cells" at a stem-cell clinic; their visual acuity before ranged from 20/30 to 20/200 and one year later "from 20/200 to no light perception", after ocular hypertension, haemorrhagic retinopathy, retinal detachment and lens dislocation (Kuriyan 2017). The FDA's consumer alert catalogues blindness, tumours and infections across the sector. None of this is nanofat, which is a surgeon's autologous procedure (previous row), and none of it is the legitimate cell-therapy research that runs under trial approval.

What a "stem-cell facial" usually contains in practice is conditioned medium from cultured cells, plant "stem cells" or an exosome preparation — cosmetics, applied topically, with the marketing borrowed from a field that has no approved cosmetic product. Limited on evidence, and the one row in this guide where the recommendation is unconditional.