Trafermin
Recombinant basic fibroblast growth factor, sold in Japan as a skin-ulcer spray, a periodontal regeneration kit and an eardrum treatment
Trafermin is the human growth factor FGF-2 (basic fibroblast growth factor) made by recombinant DNA technology. Japan approved it as Fiblast, a spray for pressure ulcers and other skin ulcers, then as Regroth, applied into bone defects during gum surgery, and as Retympa, a soaked gelatin sponge that closes a perforated eardrum. In phase 3 trials it regrew more jaw bone than placebo or the standard comparator. Given intravenously after stroke it lowered blood pressure and did not help. It is not approved in the United States or Europe.
Manufacturer's recommended dosing (Japanese label): 30 µg (5 sprays of a 100 µg/mL solution) per area up to 6 cm across, Once a day, from about 5 cm away; repeated for larger ulcers, Topical spray Details ↓
Recommended Dosing
Manufacturer's recommended dosing (Japanese label)
From the prescribing information. Other doses studied, if any, are in the full dosing data below.
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Fibroblast growth factor 2 is one of the body's own signals for wound repair: it makes blood vessels sprout and fibroblasts multiply. Trafermin is the human protein produced recombinantly, and because it is a large protein that the body breaks down quickly, it is used where it is needed, on a wound, in a bone defect or in the ear, rather than by mouth or injection into the bloodstream. When rats were given it into a vein, it gathered in the leaky capillaries of the liver, kidney and other organs and was broken down there within a day.
Its first use was Fiblast Spray, approved in Japan for pressure ulcers and skin ulcers, including burn and leg ulcers. The current Japanese package insert directs one daily treatment of five sprays from about 5 cm away for each area up to 6 cm across, and tells doctors to consider other treatment, such as surgery, if an ulcer has not improved after about four weeks. The Japanese trials the insert summarises were uncontrolled improvement-rate studies; in one, no drug reached the blood above the limit of detection after 15 days of use.
The strongest controlled evidence is in gum disease. In periodontitis the bone that holds a tooth is eaten away in pits beside the root. In two phase 3 trials published in 2016, trafermin applied once during flap surgery filled about 37% of the bone defect at 36 weeks against about 22% with placebo, and it beat enamel matrix derivative, the established regeneration product, on new bone height. Japan approved it as Regroth in 2016. Later trials combining it with bone substitutes found more bone on X-ray but no extra gain in attachment.
Retympa, approved in 2019, uses trafermin on a gelatin sponge placed in a long-standing eardrum perforation, repeated every four weeks up to four times if needed; three of four patients in its 20-patient Japanese study had a closed eardrum by 16 weeks. Doctors in Tokyo also inject trafermin into vocal folds that are paralysed or thinned with age; their retrospective series report better voice measures, but there is no randomised trial.
Trafermin has also failed. A European-Australian trial gave a 24-hour intravenous infusion within six hours of stroke and was halted after 286 patients because it was unlikely to show benefit; the higher dose lowered blood pressure and had more deaths. Because FGF-2 makes cells grow, every Japanese label forbids its use where there is, or has been, a cancer at the treatment site.
Mechanism of Action
Trafermin is the body's own repair signal FGF-2, applied where tissue needs to regrow.
Granulation tissue and new vessels
Binds FGF receptors on blood-vessel lining cells and fibroblasts, driving new vessels and granulation tissue in ulcers (Fiblast package insert, mechanism).
Bone and ligament regrowth
Placed in a periodontal bone defect it increased new bone fill against placebo and enamel matrix derivative (PMID 26547659).
Trapped and cleared locally
Binds heparan sulfate and is broken down in tissue; given into a vein in rats it was inactivated within a day (PMID 9255421).
Published Research
These studies were read from their PubMed abstracts on October 29, 2026. Cards cover studies of recombinant human FGF-2 itself. Papers titled only 'FGF-2' or 'basic fibroblast growth factor', which include the phase 2 periodontal trial and the eardrum studies, are listed under References with a reason; products made from the bovine protein are not trafermin and are not included.
Phase 3: more bone than placebo or EMD
In study A, 328 patients with periodontitis were randomised 2:1 to a 0.3% solution or placebo during flap surgery; bone fill at 36 weeks was about 37% against 22%, though gain in clinical attachment did not differ. In study B (274 patients) new bone height was 1.93 mm against 1.36 mm with enamel matrix derivative, meeting the test for non-inferiority and for superiority. No safety problems emerged.
Three strengths on a beta-TCP carrier
In 88 patients with vertical bone defects, recombinant FGF-2 at 0.1%, 0.3% or 0.4% on a beta-tricalcium phosphate scaffold was compared with the scaffold alone. The two higher strengths reached the combined success measure in 71% of patients at six months against 45% with the scaffold or the lowest strength; no antibody rise and no related serious events were seen.
In a hyaluronic acid gel
In 30 adults, each with two matched bone defects, the side treated with recombinant FGF-2 in a hyaluronic acid carrier gained more attachment (4.8 versus 2.2 mm) and lost more pocket depth after one year than the side treated with surgery alone.
Adding a bone substitute: six months
Forty-four defects were randomised to the commercial 0.3% formulation alone or combined with deproteinised bovine bone mineral. Attachment gain was similar (about 2.8 versus 3.2 mm), while bone fill on X-ray was greater with the combination (47% versus 29%).
Same trial at two years
Thirty-eight of the sites were re-examined. Both groups had kept their attachment gains (3.1 and 3.4 mm) with no difference between them, and bone fill kept rising, more with the added bone mineral (56% versus 41%). Contained defects did better on trafermin alone.
Same trial at four years
At four years, in 32 sites, attachment gains were 2.7 mm with trafermin alone and 3.5 mm with the combination, not significantly different. Bone fill was 42% against 62%, the combination doing better in defects with only one or two bony walls.
With carbonate apatite granules
In 48 defects in 38 patients with stage III periodontitis, adding carbonate apatite granules did not improve attachment gain at 12 months (3.4 versus 3.2 mm) or patient-reported outcomes, but doubled bone fill on X-ray (67% versus 32%).
Regroth with an artificial bone, exploratory
Ten patients with severe periodontitis received Regroth together with carbonate apatite granules. No adverse events related to either product occurred over 36 weeks, and bone, attachment and pocket depth all improved from their starting values.
Three-year cohort
Sixty bone defects treated with recombinant FGF-2 were followed for three years. Pocket depth and radiographic defect depth improved by six months and the gains held; the deeper the starting defect, the more bone was regained.
Systematic review: bone fill
Seven studies met the criteria. Bone fill averaged about 75% when recombinant FGF-2 was combined with a bone substitute against about 23% with the growth factor alone or controls, but pocket depth and attachment showed no added benefit from either approach.
Meta-analysis: FGF-2 and PDGF-BB
Pooling trials of recombinant growth factors for periodontal regeneration, a 0.3% strength of recombinant FGF-2 regenerated more than other strengths and more than controls.
Intravenous trial in acute stroke halted
Patients within six hours of stroke received a 24-hour infusion of 5 mg, 10 mg or placebo. The trial stopped after 286 of a planned 900 because benefit looked unlikely; 90-day deaths were 17%, 24% and 18%, and systolic pressure fell about 19 and 22 mmHg on the two doses against 8 on placebo.
Why the stroke programme stalled
The review concludes that phase 3 trials given within six hours of stroke failed because of dose-related low blood pressure and higher deaths, and argues for a new trial aimed at recovery rather than acute protection.
Vocal fold paralysis: inject early
Of 177 patients given intracordal injections at one Tokyo voice centre, 80 were analysed. Within 90 days of onset, each week's delay cost about five points of improvement on the Voice Handicap Index, so the authors recommend injecting soon after paralysis.
Vocal fold paralysis: higher doses
In 198 patients injected between 2012 and 2024, those given more than the usual 100 micrograms improved more on phonation time, airflow and voice handicap than those given the usual amount, in this retrospective comparison.
Vocal fold paralysis: lasting gains
In 221 cases, voice measures improved soon after injection and did not fade with time since injection, though the authors say the long-term data did not fully match their clinical experience.
Age-related vocal fold atrophy: one high dose
Thirty-four patients had a single injection of 50 micrograms per side. Phonation time and pitch range improved by one month and kept improving to a year; the voice handicap score worsened between six months and a year, partly with a rise in speaking pitch in men.
Atrophy: injection versus voice therapy
Using propensity-score matching on records from 197 injected patients and 412 who had voice therapy, the injected group improved more on the Voice Handicap Index; the authors call for prospective trials.
Where intravenous trafermin goes in rats
Labelled trafermin injected into rats bound to heparan sulfate in the fenestrated capillaries of the liver, kidney, adrenal, spleen, pituitary and bone marrow, was cut into three fragments there, and its active forms were gone from the liver within a day.
Dosing Data
Trafermin is a prescription drug in Japan. The first three rows are the current Japanese package inserts; the others are amounts given in published human studies, as their abstracts state them.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Trafermin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: we hold no copy of the preparation section of the label behind Trafermin's dose. Its label, named in Recommended Dosing above, is the source; the reconstitution calculator does the arithmetic for any vial.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Trafermin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Trafermin stays intact once mixed.
How it is taken
As the approved label gives it: Topical spray (Once a day, from about 5 cm away; repeated for larger ulcers; Fiblast Spray (Japan): pressure ulcers and skin ulcers (burn and leg ulcers)); Applied into the bone defect (Once, during flap surgery; Regroth Dental Kit (Japan): alveolar bone loss from periodontitis); On the eardrum (Placed in the perforation; closure checked after about 4 weeks; Retympa Set for Otology (Japan): eardrum perforation).
Source: Manufacturer's recommended dosing (Japanese label): the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Fiblast Spray (Japan): pressure ulcers and skin ulcers (burn and leg ulcers): No more than 1,000 µg a day; consider other treatment if no improvement in about 4 weeks; Regroth Dental Kit (Japan): alveolar bone loss from periodontitis: Single application; Retympa Set for Otology (Japan): eardrum perforation: Repeated if needed, up to 4 times per ear.
When effects appear: unknown; no source on this page gives a time to effect for Trafermin. Results reported in the studies are under Published Research.
Source: Manufacturer's recommended dosing (Japanese label), the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Fiblast: irritation or pain at the site, excess granulation tissue, more exudate, redness, rash and raised liver enzymes (package insert); Regroth: in its placebo-controlled phase 3, 14% had a side effect, mostly raised urine albumin and kidney-tubule markers (package insert); Retympa: ear discharge in 30% of its 20-patient study; shock and anaphylaxis are listed as possible (package insert); Intravenous use after stroke lowered blood pressure and, at the higher dose, came with more deaths (PMID 12403958); Vocal fold injection: early complications no more common than with a steroid injection (References). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Trafermin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the Japanese package inserts and the studies above”).
Interactions
Unknown: a PubMed search for human interaction studies of Trafermin (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Trafermin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Trafermin's expected mass, 17,122.4 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Not FDA Approved (Approved in Japan). Sport: Prohibited at all times (S2.3).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the Japanese package inserts and the studies above.
Contraindications & Cautions
From the Japanese package inserts (Fiblast June 2023, Regroth August 2025, Retympa February 2023).
Legal Status
Trafermin is a prescription drug in Japan only.
Frequently Asked Questions
?What is trafermin?
Recombinant human fibroblast growth factor 2 (basic FGF), the body's own wound-repair signal made by recombinant DNA technology. It is a protein of about 17 kDa.
?What is it approved for?
In Japan only: Fiblast Spray for pressure ulcers and skin ulcers, Regroth for bone lost to periodontitis (2016), and Retympa for eardrum perforation (2019).
?How well does it regrow gum bone?
In phase 3, a single application during surgery filled about 37% of the defect at 36 weeks against 22% with placebo, and gave more new bone than enamel matrix derivative. It did not improve attachment more than placebo.
?Is it used by injection?
Not on the labels. Japanese voice clinics inject it into the vocal folds off-label, with promising retrospective results. Intravenous use after stroke was tested and failed.
?Is it safe?
Local use has been well tolerated in trials. Because it makes cells grow, it is not used where there is or has been a cancer at the site, and the Fiblast label warns against long use without benefit.
?Can I get it in the US or Europe?
No. It is not approved there. Products sold as 'bFGF' elsewhere, including bovine-derived gels, are different products.
References
- [clinical-trial] Kitamura M, et al. "Randomized Placebo-Controlled and Controlled Non-Inferiority Phase III Trials Comparing Trafermin, a Recombinant Human Fibroblast Growth Factor 2, and Enamel Matrix Derivative in Periodontal Regeneration in Intrabony Defects." J Bone Miner Res, 2016;31(4):806-14. PMID: 26547659.
- [clinical-trial] Cochran DL, et al. "A Randomized Clinical Trial Evaluating rh-FGF-2/β-TCP in Periodontal Defects." J Dent Res, 2016;95(5):523-30. PMID: 26908630.
- [clinical-trial] de Santana RB, et al. "Human intrabony defect regeneration with rhFGF-2 and hyaluronic acid - a randomized controlled clinical trial." J Clin Periodontol, 2015;42(7):658-65. PMID: 25933201.
- [clinical-trial] Saito A, et al. "Treatment of intrabony periodontal defects using rhFGF-2 in combination with deproteinized bovine bone mineral or rhFGF-2 alone: A 6-month randomized controlled trial." J Clin Periodontol, 2019;46(3):332-341. PMID: 30758076.
- [clinical-trial] Aoki H, et al. "Periodontal surgery using rhFGF-2 with deproteinized bovine bone mineral or rhFGF-2 alone: 2-year follow-up of a randomized controlled trial." J Clin Periodontol, 2021;48(1):91-99. PMID: 33030228.
- [clinical-trial] Seshima F, et al. "Periodontal Regenerative Therapy Using rhFGF-2 and Deproteinized Bovine Bone Mineral versus rhFGF-2 Alone: 4-Year Extended Follow-Up of a Randomized Controlled Trial." Biomolecules, 2022;12(11). PMID: 36421696.
- [clinical-trial] Imamura K, et al. "Periodontal regenerative therapy using recombinant human fibroblast growth factor (rhFGF)-2 in combination with carbonate apatite granules or rhFGF-2 alone: 12-month randomized controlled trial." Clin Oral Investig, 2024;28(11):574. PMID: 39373727.
- [clinical-trial] Kitamura M, et al. "An exploratory clinical trial to evaluate the safety and efficacy of combination therapy of REGROTH® and Cytrans® granules for severe periodontitis with intrabony defects." Regen Ther, 2022;21:104-113. PMID: 35785043.
- [clinical-trial] Mikami R, et al. "Prognostic factors affecting periodontal regenerative therapy using recombinant human fibroblast growth factor-2: A 3-year cohort study." Regen Ther, 2022;21:271-276. PMID: 36092500.
- [review] Pouliou MM, et al. "The role of rhFGF-2 in periodontal defect bone fill: A systematic review of the literature." J Periodontal Res, 2023;58(4):733-744. PMID: 37130815.
- [review] Li F, et al. "Evaluation of Recombinant Human FGF-2 and PDGF-BB in Periodontal Regeneration: A Systematic Review and Meta-Analysis." Sci Rep, 2017;7(1):65. PMID: 28246406.
- [clinical-trial] Bogousslavsky J, et al. "Fiblast (trafermin) in acute stroke: results of the European-Australian phase II/III safety and efficacy trial." Cerebrovasc Dis, 2002;14(3-4):239-51. PMID: 12403958.
- [review] Paciaroni M, et al. "Trafermin for stroke recovery: is it time for another randomized clinical trial?." Expert Opin Biol Ther, 2011;11(11):1533-41. PMID: 21883031.
- [clinical-trial] Hasegawa T, et al. "Timing of Intracordal Trafermin Injection in Patients With Vocal Fold Paralysis: Recommendations for a New Treatment Time Course." J Voice, 2024. PMID: 39638665.
- [clinical-trial] Hasegawa T, et al. "Investigation of Optimal Trafermin Dosage and Pre-Injection Factors in Vocal Fold Paralysis." Laryngoscope, 2026;136(3):1425-1432. PMID: 41128178.
- [clinical-trial] Hasegawa T, et al. "Long-term and Longitudinal Outcomes of Intracordal Trafermin Injection in Vocal Fold Paralysis." J Voice, 2026. PMID: 42498544.
- [clinical-trial] Hasegawa T, et al. "One Year Outcomes and Longitudinal Changes in Voice Improvement With Single High Dose Intracordal Trafermin Injections for Age-Related Vocal Fold Atrophy." J Voice, 2025;39(5):1368-1376. PMID: 37142528.
- [clinical-trial] Hasegawa T, et al. "Efficacy of Intracordal Trafermin Injection Using Propensity Score Matching in Age-Related Vocal Fold Atrophy." Laryngoscope, 2026;136(6):2655-2662. PMID: 41521571.
- [pubmed] Yuge T, et al. "Metabolism of the intravenously administered recombinant human basic fibroblast growth factor, trafermin, in liver and kidney: degradation implicated in its selective localization to the fenestrated type microvasculatures." Biol Pharm Bull, 1997;20(7):786-93. PMID: 9255421.
- [other] Pharmaceuticals and Medical Devices Agency (Japan), List of Approved Products, new drugs approved April 2004 to February 2026 (English edition, read October 28, 2026): Regroth Dental Kit 600 μg and 1200 μg (trafermin, genetical recombination), approved September 28, 2016, new route of administration, alveolar bone loss due to periodontitis; Retympa 250 μg Set for Otology (trafermin), approved September 20, 2019, new route of administration, tympanic membrane perforation. https://www.pmda.go.jp/files/000281190.pdf
- [other] KEGG DRUG D03362: Trafermin (USAN/INN; JAN: genetical recombination), brand Fiblast, formula C764H1201N217O219S6, molecular weight 17122.44, efficacy anti-ulcerative (skin), periodontal tissue regeneration agent. Read October 28, 2026. https://www.kegg.jp/entry/D03362
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT01217463 and NCT01217476 (phase 3, trafermin in neuropathic diabetic foot ulcer, Southern and Northern Europe, completed); NCT00734708 (phase 3, periodontal tissue regeneration, completed).
- [other] US FDA, Drugs@FDA (openFDA): no application for trafermin. Read October 28, 2026.
Sources & Citations
Studies were read from their PubMed records on October 29, 2026 (a search for trafermin, Fiblast, Regroth and Retympa returned 53 records; recombinant human FGF-2 periodontal titles were searched separately). Doses, contraindications and side effects come from the three Japanese package inserts (JAPIC, via KEGG MEDICUS) read the same day; approval dates from the PMDA list of approved products. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.