Research on antimicrobial peptides for wound healing has produced mixed results: a 34-patient trial of the human peptide LL-37 on venous leg ulcers looked promising, but a 148-patient follow-up found no healing benefit overall.[2][3] Pexiganan cream failed two phase 3 trials in 2016,[6] and no antimicrobial peptide (AMP) product is FDA-approved for wounds. A peptide spray, peceleganan, has reported positive trials in China.[7]
This page belongs to our healing peptides hub. For background on how these peptides differ, see LL-37 vs defensins vs magainin, and for AMPs as antibiotics more broadly, our guide to antimicrobial peptides research.
Bottom line
- Established: standard antimicrobial dressings (silver, iodine) may modestly improve healing of diabetic foot ulcers, but the evidence is low certainty.[9]
- Mixed: topical LL-37 helped in a small trial and missed its goal in a larger one.[2][3]
- Negative: pexiganan did not beat placebo cream in phase 3.[6]
- Promising but early: peceleganan spray and AMP-loaded dressings.[7][10]
Why researchers turned to peptides for wounds
Chronic wounds, such as venous leg ulcers and diabetic foot ulcers, often stay stuck in an inflamed state and carry bacteria that form biofilms. AMPs are attractive because they can kill a broad range of microbes and, in some cases, also help skin repair.
LL-37 is the clearest example. A 2003 study found that LL-37 rises in healing skin wounds, helps skin cells grow over the wound bed, and is absent from the edges of chronic ulcers. Blocking it in lab-grown human skin slowed wound closure.[1] That raised the question of whether adding it back would help. Read more on our LL-37 profile.
Key trials at a glance
| Peptide | Wound type | Trial | Result |
|---|---|---|---|
| LL-37 | Venous leg ulcers | 34 patients, placebo-controlled, 4 weeks | Lower two doses healed faster; highest dose no better than placebo[2] |
| LL-37 (HEAL LL-37) | Venous leg ulcers | 148 patients, phase 2b | No overall benefit; post hoc signal in large ulcers[3] |
| LL-37 cream | Mildly infected diabetic foot ulcers | Randomized, double-blind, 4 weeks | More granulation tissue; bacteria counts not reduced[4] |
| Pexiganan | Mildly infected diabetic foot ulcers | 835 patients vs oral ofloxacin | Similar improvement (85% to 90%)[5] |
| Pexiganan (OneStep-1, -2) | Mildly infected diabetic foot ulcers | 389 patients vs placebo cream | No better than placebo[6] |
| Peceleganan spray | Infected open wounds | 570 patients vs silver sulfadiazine | Higher clinical success, lower bacterial clearance[7] |
LL-37 leg ulcer trials
First-in-human trial (2014). Thirty-four people with hard-to-heal venous leg ulcers had LL-37 or placebo applied twice a week for four weeks. Healing rates were about six times higher than placebo at the lowest dose (0.5 mg/mL) and three times higher at 1.6 mg/mL, though only the lowest dose was clearly significant. Ulcer area shrank by an average 68% and 50% in those groups. The highest dose did no better than placebo, and no safety concerns were reported.[2]
HEAL LL-37 (2021). The larger phase 2b trial gave 148 patients LL-37 at 0.5 or 1.6 mg/mL, or placebo, alongside compression therapy. It found no significant healing improvement in the full group. A post hoc analysis, meaning one done after the results were in, suggested benefit in patients with large ulcers (at least 10 cm²). Some authors worked for the company developing LL-37, under the drug name ropocamptide.[3]
Diabetic foot ulcers (2023). A double-blind trial in Jakarta applied LL-37 or placebo cream twice weekly for four weeks to mildly infected diabetic foot ulcers. The LL-37 group built more healthy granulation tissue, but inflammatory markers and bacteria counts were not reduced compared with placebo.[4]
Pexiganan: the cautionary tale
Pexiganan is a synthetic, 22-amino-acid version of magainin, a peptide from frog skin. In two earlier double-blind trials with 835 patients, pexiganan cream matched oral ofloxacin for mildly infected diabetic foot ulcers, with similar rates of clinical improvement and wound healing and no significant bacterial resistance to the peptide.[5]
The company later ran two placebo-controlled phase 3 trials, OneStep-1 and OneStep-2, in 389 patients. Pexiganan plus standard wound care did no better than placebo cream plus standard care on clinical response or wound closure, and the treatment arm had higher than expected rates of bone infection and cellulitis among serious adverse events.[6] Good basic wound care alone works well for mild infections, which makes it hard for any add-on to show a difference.
Peceleganan (PL-5) spray
Peceleganan is a synthetic AMP spray developed in China. In an open-label phase 3 trial at 37 hospitals, 570 adults with infected open wounds received 2% peceleganan spray or 1% silver sulfadiazine cream. At day 8, 90.4% of the peceleganan group met the clinical success criteria vs 78.7% with the cream. However, bacteria were cleared in only 24.0% of the spray group vs 46.0% with the cream. Side effects were similar.[7]
A 2026 double-blind, placebo-controlled trial at four hospitals tested PL-5 spray with standard debridement in mild to moderate diabetic foot infections. Clinical response was higher with the spray, and clearance of drug-resistant bacteria was 71% vs 50%, but overall bacterial eradication did not differ significantly.[8]
Peptide wound dressings
Antimicrobial dressings in clinical use today are mainly silver- or iodine-based. A Cochrane review of 22 trials found that antimicrobial dressings may increase healing of diabetic foot ulcers compared with non-antimicrobial dressings (risk ratio 1.28), but rated the evidence low certainty.[9]
Peptide dressings are a research field. Scientists are embedding AMPs in hydrogels and in electrospun fibers (ultra-thin polymer mats) that release the peptide into the wound while keeping it moist.[10] These are largely at the lab and animal stage. We found no FDA-approved antimicrobial dressing based on a peptide.
Safety and legal status
- In the trials above, topical AMPs were generally well tolerated.[2][3][7]
- No AMP is FDA-approved for wound treatment. FDA lists safety concerns for compounded LL-37, including possible immune reactions, impurities and limited human safety data.[11]
Limitations
- Trials were small, short (usually four weeks) and used different endpoints.
- Several were sponsored by the developing company.
- Wound care quality in the control group strongly affects results.
What’s next
The HEAL LL-37 authors called for a trial focused on large ulcers.[3] AMP-loaded dressings are moving through animal studies.[10] Other healing peptides, such as GHK-Cu and BPC-157, have even less human wound data; see BPC-157 vs GHK-Cu and peptides vs PRP, and the GHK-Cu profile.
Questions to discuss with a clinician
- Is my wound infected, and does it need a swab or imaging?
- Would an antimicrobial dressing help my type of ulcer?
- Do I need compression, offloading or a blood flow check?
- Are there wound-healing trials I could join?
