Sculptra, hollow temple to hip dip.

The pivotal cheek trial: adults with moderate or severe cheek wrinkles at rest "were randomized 2:1 to receive PLLA-SCA injections (150 mg; 8 mL reconstitution in sterile water for injection) + 1 mL lidocaine hydrochloride (2%) … or no treatment"; responders were "significantly higher with PLLA-SCA treatment versus the no-treatment control at months 7 (66.2% versus 38.6%), 9 (70.6% versus 31.1%), and 12 (71.6% versus 26.1%)", and "treating investigators reported improvements in skin radiance (>95%), tighter appearance (>88%), and jawline contour (>85%)" (Fabi 2024). The 3D subgroup put numbers on the lift: in the severe cases, midface volume and projection changed by "+4.88 mL/+1.62 mm (left), +2.84 mL/+1.12 mm (right) versus +0.26 mL/+0.34 mm (left), +0.68 mL/+0.37 mm (right) for control" at month 9 (Fabi 2024b). Against hyaluronic acid rather than nothing, a Chinese multicentre trial of 331 people found midface volume-scale responders of "90.57% vs. 51.01%", 84.91% against 46.98% at twelve months, with "a slightly higher incidence of injection site reactions in the PLLA group, which resolved within 1-3 days" (Zhang 2025). Galderma's press release adds that 94% still showed improvement at two years (Galderma 2023).

Graded strong: two randomised, evaluator-blinded trials of a hundred to three hundred people with a year of follow-up, on the indication the regulator approved — the same grade the volume-loss guide and the biostimulator guide give it. The caveats are that the no-treatment control cannot blind the patient, that the trials are the manufacturer's, and that "improvement" on a cheek-wrinkle scale is not the same as the lift a hyaluronic cheekbone gives on the day. The filler guide covers that alternative.

The trial that created the cosmetic indication: "In this randomized, evaluator-blinded, parallel-group, multicenter study, subjects received injectable PLLA (n = 116) or collagen (n = 117) injections (1-4 visits, 3-week intervals) … Improvements (up to 25 months after last treatment) were significantly greater (P < .001) than with collagen for posttreatment months 3 to 13", in "mostly white women and subjects with Fitzpatrick skin types II and III" (Narins 2010). The investigator ratings: "Overall improvement with injectable PLLA was 100% three weeks after the final treatment, remaining above 85% through month 25. Overall IGE of improvement with human collagen declined from 94.0% at week three to 6.0% at month 13" (Brandt 2011); the patients' own: 99% at week 3, 91% at month 13, 81% at month 25 (Brown 2011). Against the modern comparator: in a 252-person double-blind trial "at 48 weeks, PLLA demonstrated a significantly higher effective correction ratio than HA (92.4% vs 59.3%)" although "HA outperformed PLLA at Week 4" (Wang 2026); in a second, 55.56% against 25.00% still corrected at 120 weeks, with the authors' warning that "long-term extension data should be interpreted in light of attrition" (Liu 2026). Gana V was non-inferior to Sculptra split-face at 6 and 24 months (Han 2023; Kim 2026), and the network meta-analysis of 13 fold trials found six-month wrinkle scores worse with hyaluronic acid than with PLLA (Li 2024).

Graded strong on three randomised comparisons and 25 months of follow-up — a grade above the nasolabial-fold guide, which grades PLLA moderate for the fold as a line because hyaluronic acid fixes it faster and more precisely and the 25-month figure came from an uncontrolled extension; with the two hyaluronic-acid head-to-heads now published, this page grades the indication itself. The fold guide's practical point stands: PLLA treats the deflation behind the fold, and the deep-dermal grid the label describes is not a line-filling technique.

The VEGA study: "At entry, the median facial fat thickness was equal to zero … The median total cutaneous thickness (TCT) increased significantly from baseline: +5.1 mm … at week 6, +6.4 mm … at week 24, +7.2 mm … at week 48, +7.2 mm … at week 72 and +6.8 mm … at week 96 … In 22 (44%) patients, palpable but non-visible subcutaneous micronodules were observed with a spontaneous resolution in six patients at week 96" (Valantin 2003). The randomised trials: 30 people, with visual-analogue scores of 7 against 1 at week 12 and lower anxiety scores in the immediate group (Moyle 2004), and nine injection-site nodules among the 27 seen 18 months on (Moyle 2006); 101 people with CT endpoints, in whom "PLA did not increase FSTV, although tissue thickness in injection planes increased modestly" — 2.2 mm at the maxilla — "an improvement observed by patients" (Carey 2007), durable at 48 weeks with a nodule incidence of 10% (Carey 2009); and 134 people whose severity scores improved without a measurable gain in quality of life (Narciso 2009). The long series: 61 men, "all … had a successful outcome" at six months with two infraorbital papules (Burgess 2005); 65 people followed three years (Levy 2008); 290 people in the five-year FACES study, with "injection-site nodules (n = 24, 8.3%) and papules (n = 25, 8.6%)" at two years, "regardless of Fitzpatrick skin type" (Bassichis 2012); retreatment needed at 21.4 months for mild and 13.0 months for severe wasting (Mest 2009).

Graded strong on the randomised trials and the 25-year record, with the systematic review's verdict that "poly-L-lactic acid is the only filler agent with grade of recommendation: B" for this indication, "best for treatment over temples and cheeks" (Jagdeo 2015). Why it matters to a cosmetic patient: the HIV face is the extreme case of the deflation Sculptra treats, and these trials are where the nodule rates, the dilution rules and the two-year duration come from.

The trial: "This randomized, no-treatment control, evaluator-blinded, multicenter clinical trial enrolled 174 participants with moderate to severe temple hollowing, randomized 2:1 … At Month 6, 96.5% of participants in the treatment group achieved an at least 1-grade improvement on the ATHS, in contrast to 0% in the control group … PLLA was safe and well tolerated, with no therapy-related adverse events reported" (Chang 2026). An open-label study with ultrasound found a significant increase in temporal volume and elasticity at eight weeks and confirmed "the injection plane was free of vasculature" (Arruda 2026). How thin the evidence was before: a systematic review of temple volumisation found 40 articles and 881 patients, "poly-L-lactic acid (n = 2)", with pain in 29.6%, bruising in 17.3% and "deeper (supraperiosteal or inter/intra-fascial) injection may be more commonly associated with masticatory pain" (Friedmann 2025). The anatomy is the reason for the caution: the superficial temporal artery, the sentinel vein and the temporal branch of the facial nerve run through it, and the safe planes are the subfascial and periosteal ones reached with a cannula (Hong 2025; Kim 2024); the one published PLLA retinal-artery occlusion followed "PLLA injection in the temporal region" (Wu 2021).

Graded moderate: one evaluator-blinded trial against no treatment, run by a manufacturer, with twelve months of follow-up. The biostimulator guide folds the temple into a strong row with the folds and cheeks; on its own trial the temple earns a grade less, and the volume-loss guide still sends first-timers to a hyaluronic gel that can be dissolved if the temple is overfilled.

The trial: "Forty healthy women were enrolled in this randomized, controlled, double-blind, multicenter study. Eligible subjects received 3 treatments every 4 weeks with either PLLA (treatment group) or saline (control group) injections, into both sides of the face … At the 12-month follow-up, there was a statistically significant increase of skin elasticity and hydration in PLLA-treated subjects … Pigmentation, erythema, and pore size were significantly decreased, whereas radiance and smoothness were significantly increased at 12 months per blinded investigator rating in this group. No treatment-related adverse events occurred" (Bohnert 2019). The cheek trial's patients reported satisfaction with "skin radiance (90% or greater), sagging (84% or greater), and firmness (91% or greater)" (Fabi 2024). A Spanish multicentre study of a newer PLLA measured the biology: "ultrasound and elastography imaging confirmed increased tissue density … and improved viscoelasticity", and the serum collagen-synthesis marker P1CP rose from 134.6 to a peak of 233.2 ng/mL at month 2 (Urdiales-Gálvez 2026). On the arm, ultrasound skin thickness rose from 1.80 to 2.70 mm at 120 days with Sculptra (Bravo 2026), and a facial "L-Lift" series found 60% of midfaces a class better on a laxity scale at 24 weeks (Hexsel 2021).

Graded moderate: one well-designed but small placebo-controlled trial, consistent with biopsy and imaging data — the grade the collagen-loss guide gives PLLA for firmness. The honest framing: a thicker, more elastic dermis over a year is what the trial measured; "skin quality" as a menu item is that, not a resurfacing. Etched lines, pigment and pores are better served by a retinoid, a laser or the actives with their own trials.

The data: in the cheek trial, "treating investigators reported improvements in … jawline contour (>85%)" (Fabi 2024); the GLP-1 regimen of two or three PLLA sessions plus one or two hyaluronic-acid sessions "significantly improved facial skin quality and enhanced contour in the cheek, jawline, and perioral areas" in 41 people, open-label (Lorenc 2026); in 12 Asian women given hyaluronic acid on the retaining ligaments with PLLA in the temple, midface and lower face, "tragus-oral-commissure length and lower-facial-contouring length decreased 281 ± 11 mm to 275 ± 10 mm … and 297 ± 14 to 292 ± 11 mm … at week 12" (Chuang 2022); the early European series used it "for the correction of nasolabial folds, mid and lower facial volume loss, jaw line laxity" with 18–24 months of correction (Vleggaar 2004); a 106-patient two-year pilot placed it in "the prejowl area, mandibular border, and mandibular angle" among other sites, with 4.7% nodules (Schierle 2011); and the chin-and-prejowl reviews list PLLA among the biostimulators that "address volume loss, enhance contours" while noting "nonsurgical treatments cannot replace surgical interventions" (Melley 2025).

Graded moderate, matching the jowls guide and the sagging-skin guide, which grade PLLA moderate for diffuse deflation; the marionette guide grades it emerging for the line itself, which is fair — the evidence is for the deflated lower face, not for a crease. The lower face is also where the perioral nodules of the early years were, so the product stays deep and away from the mobile muscles around the mouth (Vleggaar 2006).

The studies: "This multicenter, open-label study enrolled 41 subjects with cheek wrinkles and midface contour deficiencies following GLP-1 RA-driven weight loss. Subjects received 2 to 3 treatment sessions of PLLA-SCA and 1 to 2 treatment sessions of HA-LYF or HA-CON … The … regimen significantly improved facial skin quality and enhanced contour in the cheek, jawline, and perioral areas, and demonstrated objective improvement in hydration and skin radiance … with no treatment-related adverse events reported" (Lorenc 2026); and the case series: "Participants achieved 17.9% weight reduction from baseline. At D90, FLRS scores decreased from 4.5 (SD 2.2) to 2.6 (SD 1.8), and WSRS scores from 3.1 (SD 1.5) to 1.9 (SD 1.0)", with 87% satisfied (Avelar 2026). The rationale, from a Galderma-authored narrative review, is that PLLA "induces fibroblast recruitment and stimulates regeneration of collagen and elastin, and effects vasculature and adipose tissue" (Franco 2026), resting on the adipocyte gene signature (Waibel 2024).

Graded emerging, as the volume-loss guide grades the stimulator-plus-hyaluronic protocol after weight loss: no control arm, sponsor-run, nine months. The timing point matters more than the tier: a stimulator laid into a face that is still losing fat, or that will regain it when the drug stops, cannot be adjusted afterwards. The body-contouring guide covers the weight-stability clock and what regain looks like.

The PLLA chest study: "25 healthy female volunteers aged 40-to-70 years with moderate-to-severe crepiness and wrinkling of the décolletage were injected with 1 vial of PLLA at each of three treatments … At 1 month following the last treatment, compared to baseline, investigators rated 83% of subjects had improved by at least one point on the scale. Subjects rated 74% of subjects improved … At 6 months, 90% of subjects, as rated by the investigators, and 57% of subjects, as rated by the subjects, had improvement" (Wilkerson 2018). The earlier series: 36 people with neck and chest laxity, atrophy and wrinkles, "improvement was found in 81% to 100% of the 21 cases" evaluable on photographs, "after 18 months of follow-up, the results were maintained", one early nodule (Mazzuco 2009). Lanluma's post-market study: "No AEs were reported following treatment of the décolleté" (Amselem 2024). The reviews of chest injectables describe PLLA alongside hyaluronic acid and the lasers without a controlled trial of their own (Vanaman 2015); the randomised, evaluator-blinded chest trial in the class used diluted calcium hydroxylapatite, with 73.5% of women a grade better at 16 weeks (Pavicic 2024).

Graded emerging, as the décolletage guide grades it: consistent open series, no control, and a gap between the investigators' 90% and the patients' 57%. The biostimulator guide grades the neck-and-chest row moderate on the strength of the calcium hydroxylapatite trial; that trial does not transfer to PLLA. What to ask for on the chest: a higher dilution than the face, a fan under the dermis, and an injector who has treated the area before.

The series: 27 patients, "their age averaged 65.9 years", 109 sessions, 150 mg diluted in 5–8 mL, "intermetacarpal spaces were injected … in dosages ranging from 2 to 4 mL", three to six sessions, scores "from 4 to 9 (average of 6.55)", "one case of fine unnoticeable nodulations. In six cases the result has not been satisfactory" (Redaelli 2006); three practices in which "PLLA was used to improve volume loss in the hand to the satisfaction of a majority of patients … No papules or nodules were reported" (Sadick 2008); a single patient given up to 5 mL per hand in three sessions with "correction … maintained for at least 18 months" and the note that "injectable PLLA is not FDA-approved for use in the hands" (Rendon 2010). The reviews list it among the hand volumisers with hyaluronic acid, calcium hydroxylapatite and fat (Fabi 2012; Butterwick 2016), and the body review calls the data "still limited" area by area (Christen 2022). Lanluma's hand treatments produced "lumps (neck, upper arm, hand) and nodules (neck, hand, thigh)" as the most frequent events (Amselem 2024).

Graded emerging, as the hands guide grades PLLA and poly-D,L-lactic acid on the hand. The thin, mobile, tendon-and-vein back of the hand is unforgiving of a lump, and the two products with a regulatory hand indication and randomised hand trials are in that guide; PLLA on the hand is a reasonable add-on for a face patient, not a first choice.

The trial: "This was a double-blinded, split-body trial of 15 women with hip dell volume deficits. Each subject was randomized to have 1 hip dell treated with 150 mg of PLLA-SCA while the contralateral hip dell received the equivalent volume of saline. Subjects received 3 treatments at 1-month intervals and were followed for 9 months … The dermis and adipose layers increased in thickness by 26.1% and 27%. These measures, in addition to collagen and elastic fiber quality, were significantly improved compared with saline-treated hip dells, which did not change from baseline" (Zubair 2024). The series: 60 women aged 23–54, "1 to 3 treatments, spaced 4 to 6 weeks apart, and received 2 to 12 vials per session (based on the patient budget) … Poly-L-lactic acid allows for visible volume amplification, improved skin texture, and softened cellulite dimpling in the buttocks when at least 20 vials are used" (Durairaj 2020); a 20-patient body-contouring practice with a mean of 5.1 sessions, 58% of them buttocks, and one nodule (Shridharani 2021). The reviews: "a paucity of literature on this emerging treatment modality (Level 4)", with the rules "avoid injecting deeply in the danger triangle to prevent intravascular injection into the gluteal vessels or injury to the sciatic nerve … blunt cannulas, reduced pressures, smaller volumes, and retrograde delivery" (Lin 2020); expert consensus on dosing and selection (Harper 2022); a targeted technique whose outcomes "have, to date, been subjective clinical observations" (Sarubi 2023). Lanluma lists buttocks and hip dips on its label (Lanluma product information).

Graded emerging: one 15-person randomised trial for the dell, retrospective series for the buttock, and a consensus that rates its own evidence Level IV (Haddad 2025). What PLLA does here is thicken skin and fat by a quarter and soften a dell; what it does not do is project a buttock without a vial count that competes with surgery. The body-contouring guide grades fat transfer and the rest.

The trials: "31 healthy women were enrolled … Eligible subjects received 3 treatments every 4 weeks with either PLLA (treatment group) or saline (control group) injections combined with subcision, into each of the glutes or thighs … At the 3 and 6-month follow-up, there was a statistically significant change in the global aesthetic improvement scale (GAIS) compared to baseline as assessed by blinded investigators. Significant improvements were shown in the cellulite severity scale" (Swearingen 2021); "a prospective, single-center, double-blinded, split-body, clinical trial of 20 women … randomized to receive injections with up to 2 vials of PLLA-SCA or the equivalent volume of bacteriostatic water per treatment area … followed for 330 days … Treatment of the buttocks with PLLA-SCA resulted in significant reduction of depression depth, improvement in the morphological appearance of the skin, improvement in the grade of skin laxity … Treated thighs showed reduction in the depth and number of depressions" (Almukhtar 2023). The open study: 29 women, up to three vials a thigh, "at month 9, 28/29 subjects (97%) had GAIS improvement on both thighs" with no treatment-related adverse events (Beleznay 2026); and 24 women given subcision then PLLA in the same session, "no nodules or granulomas" (Mazzuco 2020).

Graded emerging, matching the cellulite guide: the trials are double-blind, which is rare in cellulite, but they are 20 and 31 women at one centre for under a year, and the larger of the two tested PLLA as an add-on to subcision. What PLLA plausibly does is thicken the lax skin over the dimples; the bands themselves are the subcision's job. The cellulite guide grades shockwave, vacuum-guided subcision and the laser alongside.

The knee trial: "Twenty female subjects between the ages of 30 and 65 years with upper knee laxity were enrolled. The patients were randomized to receive 3 treatments of PLLA in 1 knee, whereas the other knee received 3 treatments of bacteriostatic water … Statistically significant improvement as rated on the physician global aesthetic improvement scale was seen at Day 56 after final treatment in the active knee … sustained at Day 84 and Day 168 … No statistically significant difference was seen between the active and placebo knees on the subject global aesthetic score or the subject satisfaction scale" (Kollipara 2020). The arms: in the split-arm comparison of two PLLAs, "skin thickness rose significantly (Rennova Elleva: 2.06 ± 0.55 to 2.66 ± 0.53 mm; Sculptra: 1.80 ± 0.41 to 2.70 ± 0.69 mm)", elasticity up by day 90, "histology showed sparse perivascular lymphocytes and occasional macrophages, with no granulomas" (Bravo 2026); in 26 women, "an increase in dermal thickness between 23% and 70% (average value: 46%)" after two sessions of Elleva (da Cunha 2023); abdominal stretch marks, in a 40-woman four-arm trial, shrank more with PLLA than with a 1,565 nm laser (Qu 2025). The guidance: recommendations for "the neck, décolletage, arms, abdomen, buttocks, and thighs" that end with "further investigation is needed" (Haddad 2019), and a consensus that "current data support a potential benefit for the use of PLLA-SCA for the aesthetic treatment of the neck, knees, abdomen, hands and upper arms" while rating itself Level IV (Haddad 2025).

Graded emerging, as the upper-arms guide grades PLLA on the arm: the placebo-controlled knee trial is positive for the physician and null for the patient, which is the honest size of the effect — a dermis a millimetre thicker under skin that still hangs. The tightening guide and the arm lift are where a hanging arm goes.

The trials: "60 patients were randomly divided into two groups … Group A received only CO2 fractional laser treatment, whereas Group B received injections of PLLA 1, 3, and 5 months after CO2 fractional laser treatment … Group B had lower GSS scores than Group A … the improvement in rolling scars was greater than that in boxcar scars, and both were greater than those in ice-pick scars" (Zhou 2025); "In this randomized, split-face, evaluator-blinded clinical trial, 24 participants underwent two monthly FMRF sessions. Immediately after each session, a reconstituted PLLA suspension was applied to one facial half for transdermal delivery through the FMRF-created microchannels, while sterile water was applied to the contralateral side … PLLA-treated sides demonstrated statistically significant improvements in skin texture and scar volume at 6 months compared with baseline and with control sides" (Kupwiwat 2026). Alone: 22 people in a single-arm study, "percentage of patients with much to excellent improvement … ranged from 45.5% to 68.2%", one palpable nodule (Sapra 2015); 20 people over seven treatments with significant investigator-rated reductions (Beer 2007). The same delivery idea — radiofrequency microneedling pushing PLLA through its channels — thickened the dermis without losing fat in a split-face laxity trial (Wu 2024).

Graded emerging: two randomised trials of 24 and 60 people, both testing PLLA as a surcharge on a device that already works, one of them evaluator-blinded, six months of follow-up. The microneedling guide and the resurfacing guide grade the devices themselves strong for scars; PLLA is a plausible, still-small addition for the rolling scars that respond to volume, and useless for ice-picks.

The trial: "40 women with SD were randomly assigned to one of four treatment groups: (1) control, (2) PLLA, (3) 1565-nm NAFL, and (4) a combination of PLLA and 1565-nm NAFL … The overall efficacy scores for the PLLA, 1565-nm NAFL, and PLLA + 1565-nm NAFL groups were 5.70 ± 1.25, 3.60 ± 2.12, and 6.70 ± 2.21, respectively. Post-treatment evaluations demonstrated substantial decreases in SD volume from T0 to T4, with reductions of -1.96 ± 1.53 in the PLLA group, -0.70 ± 0.67 in the 1565-nm NAFL group, and -1.48 ± 1.35 in the PLLA + 1565-nm NAFL group … Histological analysis confirmed the presence of PLLA particles in the treated area without inflammatory reactions 1 month post-final injection" (Qu 2025). The body review lists striae among the "various issues" PLLA is used for, on data it calls "still limited" (Christen 2022).

Graded emerging: one randomised trial, ten women per arm, three months. The direction — a stimulator beating a non-ablative laser on atrophic marks — is biologically sensible, since a stretch mark is a dermis that tore and thinned; the size of the trial is not yet a recommendation.

The evidence for: 36 patients with neck and chest changes, photographic improvement in 81–100% of the 21 evaluable, maintained at 18 months, one early nodule (Mazzuco 2009); a 24-study, 887-patient review of neck fillers in which "poly-l-lactic acid stimulates collagen synthesis and may also improve wrinkle severity", but "heterogeneity of outcome measures, small sample sizes, and limited long-term data constrain definitive conclusions" (Bommareddy 2026). The evidence against: "Injecting PLLA into the anterior neck is an off-label procedure and may cause a higher incidence of nodule formation" (Dunn 2022); in Lanluma's 70-person body study the neck was the most-treated area and "lumps (neck, upper arm, hand) and nodules (neck, hand, thigh) were the most frequent adverse events" (Amselem 2024); the one paper on ultrasound-guided surgical removal of a PLLA nodule concerns "a patient submitted to PLLA injection for esthetic improvement of the cervical region" (Bravo 2021b). The combined protocols with microfocused ultrasound are reviews, not trials (Hart 2015).

Graded limited, as the neck guide grades it — "extrapolated from face data; neck-specific evidence is case series, with nodule risk in thin skin". The biostimulator guide grades neck-and-chest moderate on a calcium hydroxylapatite trial that does not apply here. For necklace lines, bands and laxity the neck guide grades the toxin, the devices and the neck lift; if PLLA is used on the neck at all it is heavily diluted, fanned under the dermis by someone who scans their own complications.

The record: of the twelve grade-3 nodules in 221 cosmetic patients, "9 perioral; 3 periorbital or temple … 7 were treated (5 intralesional corticosteroids; 2 surgery)", and the authors' conclusion was that "nodules occurred in perioral and periorbital regions, so incidence is reduced by avoiding these areas" (Lowe 2009); the two persistent papules in the 61-man HIV series were "in the infraorbital region as a result of the site of placement and concentration" (Burgess 2005); a periorbital granulomatous reaction "resulting in visible papules" failed medical treatment and was excised (Stewart 2007); JAMA Ophthalmology reported facial ulcers and restrictive strabismus from a delayed periorbital PLLA granuloma (Fuller 2015); in the international ultrasound series of 240 filler granulomas, "the main regions of granulomas were the lower lid, infraorbital, and medial cheek in 41.7%, the perioral region and lips in 19.2%", PLLA being 18.8% of the fillers involved (Wortsman 2025); and lip nodules across all fillers appear a mean 2.9 years after treatment (Trinh 2022). The technique consensus: "Areas above hypermobile muscles should also be avoided … Injections around the orbits or perioral region are possible, but should not be attempted without sufficient training" (Vleggaar 2006). The attempts: 28 patients given double-diluted PLLA above the infraorbital bone, satisfaction 3.37 of 5, "one patient developing a palpable, nonvisible nodule" (Firsowicz 2025); a case series softening the lid–cheek junction from the cheek side (Montes 2025); Korean women given a poly-D,L-lactic acid into the tear trough with "sustained improvements" in an open series (Wan 2025).

Graded limited: no controlled evidence, the highest nodule rates of any site, and no way to dissolve a mistake under an eyelid or in a lip. The eye-bags guide and the dark-circles guide grade the tear-trough options; the lips guide and the lip-lines guide cover the mouth; the forehead guide covers the brow, where the vessels are the reason.

What the trials enrolled: "healthy women" whose elasticity, hydration and pigmentation were measured at twelve months (Bohnert 2019); "immune-competent adults (aged >21 years) with moderate/severe cheek wrinkles" (Fabi 2024); 30 people with early laxity in an open pilot that ended at 24 weeks and concluded the technique "may be particularly suitable for patients presenting initial signs of facial skin laxity" (Hexsel 2021). What the consensus documents actually recommend is patient selection, and the 2014 consensus notes "a shift toward a younger demographic" as a reason for the recommendations rather than evidence for it (Vleggaar 2014b). What a foreign body does over time is known: particles were "still retrievable 28 months after subcutaneous application" (Stein 2015), true granulomas "may become apparent months or years post-injection and may persist and grow over time" (Vleggaar 2014), and the late nodules in one case took "over a year of treatment with oral corticosteroids and periodic intralesional steroid injections … to resolve" (O'Daniel 2017).

Graded limited, as the collagen-loss guide and the 30s guide grade early biostimulators: no evidence, a plausible-sounding story, and an irreversible product placed into a face that has not finished changing. The 30s guide lists what prevention with trials looks like; none of it comes in a vial.