"Collagen injections" draws more than 3,000 US searches a month (clickstream estimate, October 2026), and the phrase now means two different things. Historically, it meant fillers that were collagen — purified cow collagen, later human collagen — injected to fill lines. Today it is mostly used for products that contain no collagen at all and are said to make the body produce its own. This page separates the two on the public record as of 11 October 2026: what FDA approved and when, what the early collagen fillers were known for, the one collagen-containing filler that is still approved, and why the "collagen stimulators" are not collagen. It is not a treatment recommendation.
The collagen fillers, dated
FDA's premarket approval database, read through openFDA on 11 October 2026, holds the record:
| Date | Product | What it was |
|---|---|---|
| 22 Jul 1981 | Zyderm Collagen Implant (P800022) | purified bovine collagen — the first injectable filler FDA approved |
| 24 Jun 1985 | Zyplast (P800022/S011) | bovine collagen cross-linked with glutaraldehyde, for deeper lines |
| 11 Mar 2003 | CosmoDerm 1 and 2, CosmoPlast (P800022/S050) | human-based collagen, removing the bovine allergy problem |
| 27 Oct 2006 | ArteFill (P020012) | PMMA microspheres suspended in bovine collagen, for nasolabial folds |
| 27 Jun 2008 | Evolence (P070013) | porcine collagen filler, for moderate to deep facial wrinkles |
| 23 Dec 2014 | Bellafill (P020012/S009) | ArteFill renamed (2013) and approved for acne scars on the cheek |
| 7 Aug 2026 | SANAE (P020012/S051) | Bellafill's trade name changed again |
Two of these files have gone quiet. The Zyderm file (P800022) holds 46 records, and the last — a change to the glutaraldehyde cross-linker concentration — is dated 19 December 2006. Evolence's file ends with a labelling change in June 2009. Neither Zyderm, Zyplast, CosmoDerm, CosmoPlast nor Evolence appears in FDA's unique device identification database, where devices sold in the US under the identifier rules introduced from 2014 are listed. We read that as the public record of products no longer on the US market; the files themselves do not state a withdrawal date.
What the first collagen fillers were known for
The early record is unusually well documented because the developers published their own figures:
- Allergy. About 3% of people skin-tested with Zyderm developed a localised reaction to the test dose, and about 1% of treated patients showed hypersensitivity at the treatment site. Of those, 88% had antibodies against the bovine collagen and none reacted to human collagen. Most reactions followed the test or the first treatment, which is why a skin test came first (DeLustro 1987).
- Short duration. The same summary reported a median of three treatments (mean 4.4) per patient, a measure of how often the filler was topped up.
- Rare serious events. A 1991 series put abscesses at about 4 in 10,000 cases and local tissue death at about 9 in 10,000, more than half of the latter between the eyebrows, which the authors attributed to that area's blood supply rather than to allergy (Hanke 1991).
FDA's device-report database held 838 reports naming Zyderm on 11 October 2026 — a count, not a rate, built over decades of use. Collagen's other role in this history is as a yardstick: human-based collagen was the comparator in the trial behind Sculptra's 2009 cosmetic approval, described in our Sculptra explainer.
The one that still contains collagen
ArteFill, approved in October 2006, is the only collagen-containing filler with an active approval file. It is polymethylmethacrylate (PMMA) microspheres suspended in bovine collagen: the collagen carries the beads and is absorbed, and the microspheres stay. Its pivotal trial enrolled 251 people at eight US centres against a bovine collagen control; a recalled group of 69 patients reported six late adverse events in 272 treated wrinkles (2.2%) at two to five years, two of them rated severe (Cohen 2006).
Its file shows a renamed product with a long post-approval record: renamed Bellafill in August 2013; approved for acne scars on the cheek in people over 21 in December 2014; a five-year post-approval study added to the labelling in 2015; a warning on use around the eyes in 2019; labelling revised on post-market safety data in 2020 and 2023; and, on 7 August 2026, a change of trade name to SANAE. The approval records list a separate skin test accessory, which is the 1981 allergy problem still built into the product. MAUDE held 148 reports naming Bellafill and none yet under SANAE.
The "collagen stimulators" contain no collagen
Most "collagen injection" searches now lead to Sculptra (poly-L-lactic acid) and Radiesse (calcium hydroxylapatite). Neither contains collagen. They are described as stimulators, or biostimulators, because the gradual change after treatment is credited to the tissue response around the particles, including new collagen. That is a claim about mechanism, and how well the trials measured it is set out in our Sculptra explainer and in Sculptra vs Radiesse, which also compares the two materials' FDA reports. Neither has a dissolving agent.
A third, separate meaning is the injectable "skin booster" — polynucleotides, PDRN and similar — which also contains no collagen; our overview of skin boosters covers those.
Injected collagen vs collagen you swallow
Collagen supplements are hydrolysed collagen peptides taken by mouth. They are digested before they reach the skin, they are regulated as foods or supplements rather than devices, and their evidence is a different literature from anything on this page. The difference between injected collagen, collagen peptides and the short signalling peptides in skincare is laid out in peptides vs collagen.
What is and is not established
Established: injectable collagen fillers were FDA-approved from 1981 (bovine), 2003 (human-based) and 2008 (porcine); bovine collagen required a skin test because about 3% of those tested reacted; the Zyderm and Evolence approval files have had no change since 2006 and 2009 and those products are absent from FDA's device listing database; one collagen-containing filler, PMMA in bovine collagen, remains approved and was renamed SANAE in August 2026; Sculptra and Radiesse contain no collagen.
Not established: a published withdrawal date for Zyderm, Zyplast, CosmoDerm, CosmoPlast or Evolence, which the approval files do not state; and how much new collagen any stimulator produces in a person, which the trials infer rather than measure directly. Whether any filler is suitable is a conversation with a board-certified clinician.
Sources
- US FDA, Premarket Approval database via openFDA
device/pma, queried 2026-10-11:pma_number:P800022(46 records, 1981-07-22 to 2006-12-19; S011 Zyplast 1985-06-24; S050 CosmoDerm/CosmoPlast 2003-03-11; S055 cross-linker change 2006-12-19);P020012(44 records; original approval 2006-10-27; S008 trade name Bellafill 2013-08-27; S009 acne-scar indication 2014-12-23; S011 five-year post-approval study 2015-08-07; S029 periocular warning 2019-05-03; S036 2020-06-19 and S044/S045 2023 labelling revisions; S051 trade name SANAE 2026-08-07; S052 2026-05-12 names the Bellafill Skin Test accessory);P070013(Evolence, 5 records, 2008-06-27 to 2009-06-05). - US FDA, Global Unique Device Identification Database via openFDA
device/udi, queried 2026-10-11 by brand name: zyderm, zyplast, cosmoderm, cosmoplast, evolence, sanae (0 each); bellafill (2), artefill (1). - US FDA, MAUDE via openFDA
device/event, queried 2026-10-11:device.brand_name:zyderm(838),bellafill(148),sanae(0). - DeLustro F, Smith ST, Sundsmo J, et al. Reaction to injectable collagen: results in animal models and clinical use. Plast Reconstr Surg 1987;79(4):581-94. PMID 3823250.
- Hanke CW, Higley HR, Jolivette DM, et al. Abscess formation and local necrosis after treatment with Zyderm or Zyplast collagen implant. J Am Acad Dermatol 1991;25(2 Pt 1):319-26. PMID 1918471.
- Cohen SR, Berner CF, Busso M, et al. ArteFill: a long-lasting injectable wrinkle filler material — summary of the U.S. Food and Drug Administration trials and a progress report on 4- to 5-year outcomes. Plast Reconstr Surg 2006;118(3 Suppl):64S-76S. PMID 16936546.
- PubMed E-utilities searches, 2026-10-11:
zyderm[tiab] OR zyplast[tiab](123);(zyderm[tiab] OR "bovine collagen"[tiab]) AND (hypersensitivity[tiab] OR allergy[tiab] OR "skin test"[tiab]) AND (injectable[tiab] OR implant[tiab] OR filler[tiab])(35);artefill[tiab] OR bellafill[tiab](39);evolence[tiab](14);cosmoderm[tiab] OR cosmoplast[tiab](8).