How far RADIESSE (CaHA) has been confirmed as a material
Two things about this material are new in 2026. One is that on 31 March 2026 the US FDA formally approved RADIESSE diluted 1:2 for wrinkles of the décolletage (the upper chest); the other is that a trial with a control group that received no treatment at all has appeared — in 152 people across 9 sites the improvement rate at 24 weeks split 71.2% against 6.3%. This was long spoken of as a material with “nothing but small uncontrolled studies”, and that part has changed. What was approved, though, is one thing, specified down to the region and the dilution ratio, and the property that once it is in, it cannot be dissolved and reversed is unchanged.
The conclusion, first
CaHA (calcium hydroxylapatite) is a material in which fine particles of the same mineral as bone and teeth are suspended in a gel. The representative product is RADIESSE, and in Korea there is also the DCLASSY family. The particles are 25–45 micrometres, the carrier is water for injection · glycerin · carboxymethylcellulose, and the composition is 30% CaHA. On 31 March 2026 the US FDA approved RADIESSE diluted 1:2 with sterile saline for “the correction of décolleté wrinkles in adults aged 22 and over” — the first time a way of using it diluted has become a formal indication. The trial behind it randomised 152 people across 9 sites so that 116 were treated straight away and 36 had no treatment at all for 24 weeks, with the assessor blind to which side was which. At 24 weeks, wrinkles improved by one grade or more in 71.2% of the treated group and 6.3% of the untreated group. The Korean licences are RADIESSE 수허 10-1238호 and DCLASSY 제허 11-1324호, both class 4 tissue restoration material, with the stated purpose “성인 안면부 주름의 일시적 개선” (the temporary improvement of facial wrinkles in adults) (for RADIESSE, including volume restoration of the back of the hand). “Skin texture” (피부결) and “firmness” (탄력) are not in the licence wording. And there is one thing you must know before the treatment — there is no agent that dissolves CaHA.
What is new in 2026 — a trial with an untreated control group
The hardest thing in research on aesthetic treatment is comparing against people who have had nothing done. It is hard to tell someone who has come because they want the treatment that they are on the side that receives nothing for 24 weeks. So most research in this field compares people with themselves, before and after.
The trial published in 2026 solved that problem with delayed treatment — the control group was given the same treatment after waiting 24 weeks, and that is how an untreated period was secured.
| Item | Content |
|---|---|
| Design | Randomised · assessor-blinded · multicentre (9 sites) |
| Size | 152 people in total — 116 treated / 36 untreated controls |
| Method | RADIESSE 1.5 mL diluted 1:2 with 3.0 mL sterile saline · 22G cannula |
| Sessions | Three — day 1 · week 6 · week 12 |
| Region | Décolletage (the upper chest) |
| Primary outcome | The proportion improved by one grade or more on the wrinkle scale at 24 weeks |
| Item | Treated group | Untreated control group |
|---|---|---|
| Wrinkle improvement (at rest) | 71.2% (95% confidence interval 61.4–79.4) | 6.3% (1.5–22.9) |
| Wrinkle improvement (on expression) | 65.8% (55.9–74.5) | 16.0% (6.8–33.1) |
The gap between the two groups is large. And what this trial answered is the question “is it looking better because time has passed, or because of the treatment?” That the untreated group stayed at 6.3% is the answer.
There is something to state alongside it. The trial was funded by the manufacturer, and 3 of the 6 authors are employed by the manufacturer. And what was measured is a wrinkle scale, not collagen or the physical properties of the skin.
How far the licences go
The second axis for understanding this material is the licence wording. What the thing is licensed to be used for is written in an official document, not in the product literature.
In the United States, the aesthetic approvals for RADIESSE began in 2006 with the nasolabial folds and the regions have been added one at a time since.
| When | What was added |
|---|---|
| December 2006 | Facial wrinkles · folds (nasolabial folds) |
| June 2015 | Volume restoration of the back of the hand |
| September 2021 | Jawline contour |
| March 2026 | Décolleté wrinkles — dilution 1:2 with sterile saline specified |
What makes the March 2026 approval unusual is that the practice of diluting went into the indication wording itself. Until then dilution was use outside the licence. Conditions are attached to this approval, though — the product is to be supplied only to practitioners who have completed training for that indication, and it is stated that it must not be injected over breast tissue.
The Korean licences are as follows. These are what we confirmed in the Ministry of Food and Drug Safety licence records.
| Product | Licence number | Stated purpose (licence wording) |
|---|---|---|
| RADIESSE | 수허 10-1238호 | “합성 칼슘 하이드록실아파타이트를 피하에 주입하여 물리적인 수복을 통해 성인 안면부 주름의 일시적 개선 및 볼륨이 감소된 손등의 일시적 볼륨 회복” (“synthetic calcium hydroxylapatite injected subcutaneously, for the temporary improvement of facial wrinkles in adults through physical restoration, and temporary volume restoration of the back of the hand where volume has been lost”) |
| RADIESSE + lidocaine | 수허 17-91호 | As above but containing lidocaine · the temporary improvement of facial wrinkles |
| DCLASSY | 제허 11-1324호 | “하이드록시아파타이트 기반의 하이드로겔을 피하에 주입하여 물리적 수복을 통해 성인의 안면부 주름을 일시적으로 개선” (“a hydroxylapatite-based hydrogel injected subcutaneously, to temporarily improve facial wrinkles in adults through physical restoration”) |
The licence wording says three things at once — where (피하에, subcutaneously), how (물리적인 수복을 통해, through physical restoration) and what (안면부 주름의 일시적 개선, the temporary improvement of facial wrinkles). “Skin texture” (피부결), “firmness” (탄력), “regeneration” (재생) and “skin booster” (스킨부스터) are in none of the three licences.
This is not a matter peculiar to this product. Even a hyaluronic acid product with “skin booster” in its name has, as its Korean licensed purpose, “입술주위 잔주름의 일시적 개선” (the temporary improvement of fine perioral lines). The Ministry does not use “skin texture” or “firmness” themselves as indication wording. How to check a licence number yourself is set out in checking a licence number directly.
One thing to add — the spelling commonly used in Korea, “디클래씨”, is 디클래시 (DCLASSY) in the licence, and the manufacturer is CGBio ((주)시지바이오). And this licence was obtained in 2011, with nine product names sharing the one licence, VOLassom and Facetem among them. That is, it is not a newly arrived material but another name for a 15-year-old licence.
Where it is put decides the result
With this material the difference in the material by region is especially marked. Set the reported rates of nodules (lumps you can feel) side by side for licensed regions and unlicensed ones and it comes out like this.
| Region | Nodule rate | Licence |
|---|---|---|
| Back of the hand | 0% (pivotal trial) | Licensed region |
| Nasolabial fold | 0.9% (1 of 117) | Licensed region |
| Décolletage | 2.2% (3 of 137) · all resolved without sequelae | Licensed region (2026–) |
| Lip mucosa | 12.4% (42 of 338) | Outside the licence |
The 12.4% for the lips is a figure from a study following 609 people, and it was 8.8% even when the injected volume was reduced. Another study following 1,000 people over 52 months reported that nodules were almost entirely confined to the lips, and only two people had one outside the lips.
This contrast is the most practical part of this piece. It is the same material, and yet in licensed regions it is around 1% and outside them ten times that. More than whether the material is safe or dangerous, where and how it is put decides the result. The US FDA instructions for use likewise state that safety and effectiveness have not been established in the lips and the periorbital area.
This is why we use this material only within the licensed regions and purposes. On nodules themselves we have written separately in why nodules form.
That it cannot be reversed — the one thing to know before the treatment
A hyaluronic acid filler can be dissolved with a drug called hyaluronidase if something goes wrong. This is the great advantage of hyaluronic acid fillers, and many people know it as “fillers can just be dissolved”.
CaHA is different. A 2024 paper on this material wrote in its conclusion that there is no agent that reverses CaHA — “there is no reversal agent for CaHA”. The first author of that paper is employed by the manufacturer.
A misunderstanding arises often at this point. In actual practice hyaluronidase is injected for CaHA vascular complications too. So it comes to be known as something that “can be dissolved”. It is true that it is used, but the reason is a different one.
| Hyaluronic acid filler | CaHA | |
|---|---|---|
| What it does | Breaks down the causative substance itself | Reduces oedema and increases blood flow so the tissue can hold out |
| The blocking substance | Is gone | Remains as it was |
| The aim | To clear what is blocked | To keep the surrounding tissue alive |
A consensus document by 17 international experts recommends hyaluronidase for CaHA vascular complications as well, and states the reason for it explicitly as being to increase blood flow in the area through reduced oedema · capillary permeability · anti-inflammatory action. In an experiment using cadaveric arteries, even a solution containing hyaluronidase failed to dissolve the CaHA inside the artery.
So what is done if something goes wrong — the published method is not to dissolve it but to disperse it. Sterile saline or sterile water is injected into the lump and it is massaged firmly to break up the aggregated particles; the largest effect reported was a reduction of about 35%. The step after that is drug injection and laser, and the last is surgical removal. The substance itself is absorbed gradually over something like two years.
We do not set this down because it is negative information. We set it down because it is an item to know and decide on before the treatment. Hyaluronic acid fillers and CaHA are materials of different character in whether they can be reversed, and that is why we keep the region and the volume conservative. Hyaluronidase itself is set out in what dissolving with hyaluronidase means.
How far the story that collagen increases has been confirmed
CaHA is spoken of as a material that increases collagen as well as filling volume. Histological grounds in that direction do exist.
- In tissue from 5 people in whom CaHA was injected into skin due for abdominoplasty and excised 2 months later, the proportion of newly formed type III collagen increased significantly (P < 0.01). Untreated tissue from the same people was mostly mature type I collagen.
- In a study of 20 people given diluted CaHA in the neck and décolletage, type I collagen and elastin increased significantly at 4 months and 7 months. Type III collagen rose sharply at 4 months and fell back by 7 months, but remained higher than before the treatment.
The often-quoted figure of “a 160% increase in total collagen”, though, should be read carefully. We followed it back to its source and that number is not written in the primary paper. It was a value the authors of a later review read off a graph in the primary paper and converted, and in that primary paper the number of people biopsied was one, the region was the thigh, not the face, the diluent was lidocaine, not saline, and the period was 90 days. What the primary paper actually reported was a 103% increase in type I collagen at 1:1 dilution, and total collagen rose most at 1:1, the most concentrated end.
That last part matters in practice. In the field it is common to use it thinner, at 1:4 or 1:6, but the two pieces of material that actually compared dilution ratios both point to the more concentrated side — the one-person study above at 1:1, and a controlled animal experiment at “up to 1:3”. We did not find comparative material showing that diluting to 1:4 or thinner is better.
How far the collagen-stimulating materials have been confirmed as a family is set out in collagen boosters, what is confirmed family by family, and the behaviour of microparticle materials in the kinds of PCL product.
In summary — what is confirmed and what is not yet
Confirmed
- On 31 March 2026 the US FDA approved RADIESSE diluted 1:2 for décolleté wrinkles (aged 22 and over). Conditions were attached: supply only to practitioners who have completed the training, and no injection over breast tissue.
- In a randomised · assessor-blinded trial of 152 people across 9 sites, the improvement rate at 24 weeks was 71.2% in the treated group against 6.3% in the untreated group.
- The Korean licences are RADIESSE 수허 10-1238호 (facial wrinkles + back of the hand) and DCLASSY 제허 11-1324호 (facial wrinkles), both class 4 tissue restoration material.
- The nodule rate differs greatly by region — back of the hand 0% · nasolabial fold 0.9% · décolletage 2.2% · lips 12.4%.
- There is no agent that reverses CaHA. The hyaluronidase used for vascular complications is not there to dissolve the substance but to keep the tissue alive.
- In human tissue, an increase in type III collagen (5 people, 2 months) and an increase in type I collagen · elastin (20 people, 4 · 7 months) have been confirmed.
Inferred
- The result confirmed in the décolletage appears likely to apply to some degree in other regions of similar character, but that is an inference. What was approved is the décolletage.
- That nodules differ so much by region appears to be related to the thickness of the skin and to how much that region moves. There is an explanation that particles gather more easily in a region that moves repeatedly.
What we could not confirm
- A trial comparing “hyperdiluted use improves skin texture and firmness” against an untreated control group — we did not find one. What the 2026 trial measured is a wrinkle scale.
- Grounds for thin dilution ratios such as 1:4 or 1:6 — we did not find material comparing the ratios, and the two pieces that exist point to the more concentrated side.
- Treatment intervals and the number of sessions on the face · neck — apart from the décolletage (day 1 · week 6 · week 12) we did not find a comparatively validated protocol.
- The original text of the method of use in the Korean licence annex — it is withheld from publication by the Ministry, so we were unable to confirm the Korean licence wording on dilution ratio and injection depth.
Material pointing the other way
- The histology studies reporting increases in collagen · elastin are concentrated in a few research groups, and the review that gathered them has all 6 authors with an interest in the manufacturer and was funded by the manufacturer.
- In a 5-person study comparing Sculptra (PLLA) against CaHA on opposite arms, there were no clinical differences between the two materials, and an inflammatory reaction of moderate degree or above was observed on both sides.
- CaHA is a material clearly visible on CT. In a 58-person facial CT study it did not obscure the structures beneath, but there is a report that it can look like a false positive on PET — if you are under follow-up imaging for cancer, you should tell the radiology department that you have had the treatment.
- Vascular complications are rare but reported, and recovery rates for visual loss are low. For that reason the glabella is a contraindication for this material, and the nasal tip and ala are listed as regions not recommended.
Frequently asked questions
Is RADIESSE a filler or a skin booster?
Under the licence it is a tissue restoration material, that is, a filler. The Korean licensed purpose is “피하에 주입하여 물리적인 수복을 통해 성인 안면부 주름의 일시적 개선” (injected subcutaneously, for the temporary improvement of facial wrinkles in adults through physical restoration), and “skin texture” (피부결) and “firmness” (탄력) are not in the wording. A collagen-stimulating action has been confirmed alongside it, though, so it can be seen as a material with both characters. the difference between a filler and a booster may help as a reference.
Can it be dissolved?
No. This is the decisive difference from a hyaluronic acid filler. If a vascular complication occurs hyaluronidase is injected, but not in order to dissolve the CaHA — it is to reduce oedema, increase blood flow and keep the tissue alive. The blocking substance itself remains. When a lump forms, the method used is to inject sterile saline and disperse it, and the largest effect reported was a reduction of about 35%.
How long does it last?
A study gathering the literature systematically reports 12–18 months. The expression “two years” is used often, but that is closer to the period the substance remains in the body than the period the effect is maintained. The two are different statements. The décolletage approval material also observed only out to 84 weeks and does not say what happens after that.
What do I do if a nodule forms?
First, the probability differs a great deal by region — in the licensed nasolabial fold it was 0.9% and the back of the hand 0%, while in the unlicensed lips it was 12.4%. When one does form, the method used first is injecting sterile saline or sterile water and dispersing it by massage, with drug injection or laser if needed. Above all it is better to come early — once time passes and collagen attaches, it becomes harder to break up.
Are DCLASSY and RADIESSE the same thing?
Both are CaHA materials and their licence classification is the same (class 4 tissue restoration material). The manufacturers differ, though — RADIESSE is from Merz in the United States, DCLASSY from CGBio in Korea. And the DCLASSY licence was obtained in 2011, with nine product names including VOLassom sharing the one licence. It is not a new material but another name for an old licence.
What about hyperdiluting it and placing it over the whole face?
What the US FDA approved in March 2026 is the case of a 1:2 dilution in the décolletage. Using it more thinly diluted on the face or neck for the purpose of “skin texture” is not included in the licensed purpose. On top of that, the two pieces of material that compared dilution ratios suggest, if anything, that the concentrated side (1:1–1:3) is better. We use this material within the licensed regions and purposes.
I heard collagen increases by 160%?
The 160% is not written in the primary paper for that figure. It is a value a later review read off a graph in the primary paper and converted, and in that primary paper the number of people biopsied was one and the region was the thigh. What the primary paper actually reported is a 103% increase in type I collagen (1:1 dilution). It is true that collagen increases, but this particular number rests on thin grounds.
Does it hurt?
There are products containing lidocaine, and anaesthetic is used alongside before the treatment. The common reactions reported are bruising · swelling · redness, and they usually settle within a few days. On bruising and swelling we have written in bruising and swelling.
Does it affect CT or mammography?
CaHA is a material that shows up on imaging. In a 58-person study of facial CT it did not obscure the structures beneath and was reported to be unlikely to be confused with a lesion. Cases where it appeared as a false positive on PET have been reported, however, and the décolletage approval document itself records that imaging interference in the breast region has not been investigated. When you go for imaging, please tell them that you have had the treatment.
Are there regions where it should not be used?
The glabella is a contraindication and the nasal tip · ala are not recommended — because of vascular complications. The US instructions for use state that safety and effectiveness have not been established in the lips and the periorbital area, and the nodule rate in the lips has in fact been reported at 12.4%. If you have a history of breast cancer or an autoimmune · granulomatous disease, please be sure to tell us before the treatment.
Who wrote this
Written and reviewed by Lee Chi-Hak, MD, medical director of Miso Clinic in Daegu, South Korea. Every study cited above is given together with its design, its size and the limitations the authors themselves recorded, and where we could not find data, we have said that we could not find any.
| Medical director | Lee Chi-Hak, MD |
|---|---|
| Address | 4F Bombom Building, 125 Dongdeok-ro, Jung-gu, Daegu, South Korea · Exit 1, Kyungpook National University Hospital Station |
| Phone | +82-53-428-2700 |
| Hours | Weekdays 11:00–19:00 (lunch 13:00–14:00) / Saturday 10:00–16:00 (no lunch break) / Closed Sundays and public holidays |
| Columns | All clinical columns |
| Reference library | All booster and device references |
References
- The randomised trial with an untreated control group — Fabi S, Moradi A, Hill D, Odena G, Kim SW, Graul V. Aesthetic Surgery Journal 2026 (online 9 July), DOI 10.1093/asj/sjag142, PMID 42424535, trial registration NCT05163353. Randomised · assessor-blinded · multicentre (9 sites) · 152 people in total (116 treated / 36 untreated, delayed-treatment controls). RADIESSE 1.5 mL diluted 1:2 with 3.0 mL of 0.9% sterile saline, 22G cannula, three sessions on day 1 · week 6 · week 12. The control group had no treatment to 24 weeks and then the same treatment. Primary outcome (24 weeks, improvement of one grade or more on the décolleté wrinkle scale) — treated 71.2% (95% CI 61.4–79.4) against control 6.3% (1.5–22.9), difference 65.0 (45.6–74.4). Wrinkles on expression 65.8% (55.9–74.5) against 16.0% (6.8–33.1). Interests — 3 of the 6 authors are employed by the manufacturer, and the trial was sponsored by Merz North America. Limits — what was measured is a wrinkle scale, not collagen · elastin histology or the physical properties of the skin, and 35 of the 116 in the treated group (30.2%) did not complete the trial.
- The randomised trial comparing treatment intervals — Pavicic T, Kerscher M, Kuhne U, Heide I, Dersch H, Odena G, Graul V. Journal of Drugs in Dermatology 2024;23(7):551–556, DOI 10.36849/JDD.8261, PMID 38954627, NCT04177212. Randomised · assessor-blinded · multicentre, 117 people, 1:2 dilution. There is no untreated control group; what was randomised is the treatment interval (3 sessions 8 weeks apart against 2 sessions 16 weeks apart) — both groups were treated. Response rate 16 weeks after the last session 73.5% (pooled sample, P < 0.0001).
- The US FDA approval wording — The aesthetic indications for RADIESSE fall under PMA P050052 (2006-12-22, facial wrinkles · folds), with all subsequent extensions belonging to it — back of the hand 2015-06-04 (supplement S049), jawline 2021-09-01 (S129), décolleté 2026-03-31 (S162). The décolleté approval wording — “RADIESSE Injectable Implant diluted 1:2 with 0.9% sterile saline solution … for the correction of décolleté wrinkles in patients 22 years of age and older”. Conditions — supply only to practitioners who have completed training for that indication, “Injections should not be made in an area overlying or including breast tissue.”, and a post-market study obligation (NCT07086248). A separate PMA, P050037 (approved the same day), is for the HIV facial lipoatrophy indication. Note — there is no FDA approval history for the neck, and no approval specific to the microcannula. The instructions for use state that safety and effectiveness have not been established in the lips and the periorbital area.
- The Korean product licences — Confirmed in the Ministry of Food and Drug Safety medical device licence records. RADIESSE — 수허 10-1238호 (2010-11-17, tissue restoration material, classification B04230.02, class 4, imported by Merz Asia Pacific, manufactured by Merz North America). Stated purpose, original wording — “합성 칼슘 하이드록실아파타이트를 피하에 주입하여 물리적인 수복을 통해 성인 안면부 주름의 일시적 개선 및 볼륨이 감소된 손등의 일시적 볼륨 회복” (“synthetic calcium hydroxylapatite injected subcutaneously, for the temporary improvement of facial wrinkles in adults through physical restoration, and temporary volume restoration of the back of the hand where volume has been lost”). RADIESSE + lidocaine — 수허 17-91호 (2017-03-07, a combination drug · device item). DCLASSY — 제허 11-1324호 (2011-12-05, tissue restoration material, class 4, manufactured by CGBio ((주)시지바이오)) — “하이드록시아파타이트 기반의 하이드로겔을 피하에 주입하여 물리적 수복을 통해 성인의 안면부 주름을 일시적으로 개선” (“a hydroxylapatite-based hydrogel injected subcutaneously, to temporarily improve facial wrinkles in adults through physical restoration”). Nine product names are registered under this licence — 볼라썸 · VOLassom · Facetem · NUIT · Facetem S · VoLassom CaHA · DCLASSY CaHA 0.8 · DCLASSY CaHA 1.5 · LUMICA. For comparison — even a hyaluronic acid product with “skin booster” in its name (수허 22-105호, 2022-05-09) has as its licensed purpose “성인의 얕은에서 중간 입술주위 잔주름을 일시적으로 개선” (“to temporarily improve shallow to moderate fine perioral lines in adults”). What we could not confirm — the licence annex (method of use · performance) is designated as withheld from publication, so we were unable to confirm the Korean licence wording on dilution ratio and injection depth. On wording — the Medical Devices Act restricts advertising to the scope of the licensed purpose. What we have set down goes as far as “it is not included in the licensed purpose”, and the lawfulness of use under a physician’s clinical judgement is a separate question from this.
- Nodule rates by region — Jansen DA, Graivier MH. Plastic and Reconstructive Surgery 2006;118(3 Suppl):22S–30S, PMID 16936541 — retrospective, 609 people, followed at 6 months and 12–24 months. “nodules, reported by 42 of 338 of lip mucosa augmentation subjects (12.4 percent) and six of 163 of subjects (3.7 percent) who had treatment for radial lip lines”, and 8.8% when the injected volume was reduced. / Tzikas TL. Dermatologic Surgery 2008;34 Suppl 1:S9–S15, PMID 18547188 — 1,000 people · 52 months, “chiefly confined to the lips”, with 2 people having nodules outside the lips. / Pivotal trial figures — nasolabial fold, nodules in 1 of 117 (0.9%, control also 0.9%, granuloma 0%); décolletage, injection site mass in 3 of 137 (2.2%, 2 of them persisting beyond 28 days, zero severe · all resolved without sequelae); back of the hand 0%. / Meta-analysis across biostimulators in general — Smith L et al., Aesthetic Surgery Journal 2025;45(12):1278–84, PMID 40674466 — nodules 5%, bruising 27%, erythema 16%. All 25 included papers are observational, however, and the heterogeneity between studies is very high (I² = 87.3%).
- That it cannot be reversed — McCarthy AD, van Loghem J, Martinez KA, Aguilera SB, Funt D. A Structured Approach for Treating Calcium Hydroxylapatite Focal Accumulations. Aesthetic Surgery Journal 2024;44(8):869–879, DOI 10.1093/asj/sjae031, PMID 38366791. The original wording in the conclusion — “there is no reversal agent for CaHA”. The first author is employed by the manufacturer. The steps of management — (1) no intervention and natural absorption (2) injection of sterile saline · sterile water followed by mechanical dispersion (reductions reported: massage alone about 10%, with saline about 20%, with sterile water about 35%) (3) drug injection · laser (4) puncture and expression · surgical removal. “Hyaluronidase” and “dissolve” do not appear once in the 51 pages of the US instructions for use — the only sentence about removal is that surgical removal may have to be attempted in the case of infection. A nodule arising from hyperdilution is aggregated particles rather than gel, so it does not drain away like gel with time, and once collagen forms it binds the particles more firmly, so it is better to treat it early, as the same paper records.
- That the reason for using hyaluronidase is a different one — van Loghem J, Funt D, Pavicic T, Goldie K, Yutskovskaya Y, Fabi S et al. Managing intravascular complications following treatment with calcium hydroxylapatite: An expert consensus. Journal of Cosmetic Dermatology 2020;19(11):2845–2858, DOI 10.1111/jocd.13353, PMID 32185876. 17 experts · modified Delphi. It states the reason for recommending hyaluronidase explicitly as “reduced oedema · capillary permeability · anti-inflammatory action”, and records that these together increase blood flow in the area and aid wound healing — not because it breaks CaHA down. The glabella is stated as a contraindication and the nasal tip · ala as regions not recommended. On steroids the authors themselves wrote that “there is no evidence that they improve the outcome of ischaemia”. / A direct test — Yankova M, Pavicic T, Frank K, Schenck TL, Beleznay K et al., Aesthetic Surgery Journal 2021;41(5):NP226–NP236, DOI 10.1093/asj/sjaa350, PMID 33544840 — human cadaveric facial arteries filled with CaHA and immersed for 24 hours. Even a solution combining sodium thiosulfate and hyaluronidase failed to dissolve the CaHA inside the artery. / Sodium thiosulfate — Danysz W et al., Clinical, Cosmetic and Investigational Dermatology 2020;13:1059–1073, PMID 33408497 (live pigs · controlled experiment, no evidence of degradation was obtained and necrosis · haemorrhage were observed, 5 of the 8 authors employed by the manufacturer). Merkel EA et al., Journal of Investigative Dermatology 2022;142(11):3125–3127, PMID 35526562 — human skin from 8 people, the diffusion distance did not differ from saline (2.87 ± 0.82 against 2.88 ± 0.78 mm), “there is currently no reversal agent for CaHA”.
- The histological material on collagen · elastin — Zerbinati N, Calligaro A. Clinical, Cosmetic and Investigational Dermatology 2018;11:29–35, DOI 10.2147/CCID.S143015 — 5 people, CaHA 0.3 mL injected into skin due for abdominoplasty and excised at 2 months. Untreated sites in the same patients served as the control. On picrosirius red staining with circularly polarised microscopy, the proportion of type III collagen increased significantly (P < 0.01), while the control tissue was mostly mature type I collagen. This was undiluted CaHA. / Yutskovskaya YA, Kogan EA. Journal of Drugs in Dermatology 2017;16(1):68–74, PMID 28095536 — 20 people · single arm · no control group, neck · décolletage, dilutions of 1:2 / 1:4 / 1:6, biopsies at 4 months · 7 months. Type I collagen and elastin increased significantly at 4 months (P < 0.05) and 7 months (P < 0.00001), and type III collagen increased significantly at 4 months (P < 0.00001) and then fell by 7 months, though remaining higher than before the treatment. Note — this study did not compare the three dilution ratios against one another. It assigned them by skin thickness only, and reported the results with the 20 people pooled. The paper is paywalled, so we were unable to confirm the funding source and the conflict of interest declaration. / Guida S et al., Dermatologic Therapy 2021;34(5):e15090, PMID 34363289 — 20 people, 1:2 dilution, neck, 3 months of follow-up, no control group, using an unvalidated scale newly proposed by the authors.
- The source of “a 160% increase in total collagen” — Following it back, this number does not exist in the primary paper. The primary paper is Casabona G, Pereira G, Plastic and Reconstructive Surgery – Global Open 2017;5(7):e1388, DOI 10.1097/GOX.0000000000001388, PMID 28831339. The region is not the face but cellulite of the buttocks · thighs, the clinical part is retrospective, 20 people · no control group · 90 days, and the number of people biopsied is one, a patient due for thigh surgery. Six dilution ratios were injected at 0.3 mL each into the inner aspect of that one person’s two thighs and the excised tissue was recovered 90 days later, and the diluent was 2% lidocaine, not saline. The values the primary paper reported are a 103% increase in type I collagen at 1:1 dilution and 93% at 1:0.6, and the maximum for total collagen came at the 1:1 dilution. The “160%” is a later review reading the bar chart in the primary paper’s figure as an approximate value and converting it. That review is Aguilera SB, McCarthy A, Khalifian S, Lorenc ZP, Goldie K, Chernoff WG, Aesthetic Surgery Journal 2023;43(10):1063–1090, PMID 37635437, which states of itself that it is a narrative review, has all 6 authors with an interest in the manufacturer (one an employee, the rest advisory · speaking) and gives its funding source as “supported by Merz Aesthetics North America”. It is not a systematic review.
- On dilution ratios — There are two pieces of material that actually compared the ratios. (1) Casabona 2017 above — one person, six ratios, total collagen highest at 1:1. (2) Botsali A et al., Dermatologic Surgery 2023;49(9):871–876, PMID 37399137 — a pig experiment · with a negative control group, a dose response over 1:3–1:19, with the effect “more marked up to a 1:3 dilution”. That is, we did not find comparative material showing that the 1:4 · 1:6 common in the field is better, and the two pieces that exist point to the more concentrated side.
- Material pointing the other way — Mazzuco R, Evangelista C, Gobbato DO, de Almeida LM. Journal of Cosmetic Dermatology 2022;21(12):6727–6733, PMID 36098704 — 5 women, PLLA on one arm and CaHA on the other, three sessions. “there were no clinical differences between these two fillers”; at the end point 2 people were better on the PLLA side, and a moderate to marked lymphocyte · giant cell infiltrate was observed on both sides. New collagen was confirmed only in the subcutaneous tissue around the particles, with no change in the dermis. / Imaging — Feeney JN, Fox JJ, Akhurst T, Clinical Radiology 2009;64(9):897–902, PMID 19664480 (Memorial Sloan Kettering) — in 5 people on FDG PET/CT, CT attenuation 280–700 HU, SUV 2.9–13.4, “a potential cause of a false-positive imaging study”. Against that, Carruthers A et al., Dermatologic Surgery 2008;34 Suppl 1:S78–S84, PMID 18547186 — 58 people, read by 2 blinded radiologists, “did not obscure the underlying structures and there was no evidence of migration”. The décolletage approval document states that imaging interference in the breast region itself has not been investigated. / Vascular complications — Doyon VC, Liu C, Fitzgerald R, Humphrey S, Jones D, Carruthers JDA, Beleznay K, Aesthetic Surgery Journal 2024;44(10):1091–1104, PMID 38630871 — 365 new cases of visual loss across fillers in general; of the 318 with a reported outcome, full recovery 6.0% · partial recovery 25.8% · no recovery 68.2%, “No treatments were significantly associated with visual improvement”. For CaHA, at least 11 cases of vascular occlusion with visual loss have been reported (Young SM et al., Aesthetic Plastic Surgery 2025;50(5):1994–2005, PMID 41263987) — mostly the nasal dorsum.
- What we were unable to confirm — (1) A trial comparing “hyperdiluted CaHA improves skin texture · firmness” against an untreated control group — we were unable to confirm one (2) material comparing treatment intervals and numbers of sessions on the face · neck (3) the original text of the method of use in the Korean licence annex (withheld) (4) the funding source · conflict of interest declaration of Yutskovskaya 2017 (paywalled) (5) a prospective study measuring the point of complete disappearance of CaHA in humans — “2.5 years” is a statement in a review, not a measured value (6) whether there is truly no medical device in Korea with “skin texture · firmness” as its stated purpose — the Ministry’s search does not support full-text search of stated purposes, so we confirmed only that it is absent from the licence wording of the two products above.
- Continuing pieces — collagen boosters, what is confirmed family by family, why nodules form, what dissolving with hyaluronidase means, the kinds of PCL product.
Everything in this column is general information and does not replace medical diagnosis or treatment. Effects and side effects vary with individual skin condition, age and underlying illness, and the same result is not guaranteed for everyone. Any decision to proceed should be made in an in-person consultation with a physician.
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