Combined therapy using a PRP-FG-containing repair gel and oral methylene blue (administered as leucomethylene blue) 'may provide a safe and effective approach to treating hard-to-heal DFUs.'
Key Findings
Results
A significant increase in transcutaneous oxygen tension was observed in patients treated with combined PRP-FG gel and oral methylene blue, indicating improved tissue oxygenation.
The increase in transcutaneous oxygen tension reached statistical significance at p=0.034
Transcutaneous oxygen tension was used as an objective measure of tissue oxygenation
This finding was observed over the 12-week treatment period
All six enrolled patients had not responded to standard therapies for at least four weeks prior to the study
Results
Participants demonstrated reduced wound area and improved wound bed condition over the 12-week treatment period.
The study was a single-centre, self-controlled pilot study comparing the new intervention to previous standard care
A total of six patients were enrolled, of whom four completed the full 12 weeks of treatment
Weekly follow-up visits were conducted to assess wound healing progress
All participants had hard-to-heal DFUs that had not responded to standard therapies for at least four weeks
Results
Participants experienced reductions in wound exudate, pain, and malodour within the first week of treatment.
These symptomatic improvements were observed within the first week of initiating the combined therapy
Treatment consisted of PRP-FG repairing gel dressing combined with 35mg of methylene blue dissolved in 200ml of infant formula milk, administered as leucomethylene blue (LMB)
No serious adverse events were reported during the follow-up period
The rapid symptomatic improvement occurred before the full 12-week treatment period was complete
Methods
The study enrolled a small pilot cohort of six patients with hard-to-heal diabetic foot ulcers, of whom only four completed the full treatment protocol.
This was a single-centre, self-controlled (non-randomised) pilot study design
Inclusion criteria required patients to have DFUs that had not responded to standard therapies for at least four weeks
The treatment protocol consisted of 12 weeks of combined PRP-FG gel dressing and 35mg oral methylene blue (as LMB) daily
Two of six enrolled participants did not complete the 12-week treatment period
The self-controlled design compared outcomes to each participant's own previous standard care response
Methods
Methylene blue was administered orally in the form of leucomethylene blue (LMB), dissolved in 200ml of infant formula milk at a dose of 35mg.
The use of infant formula milk as a delivery vehicle for LMB was a specific aspect of the administration protocol
Methylene blue was administered as leucomethylene blue (LMB), which is the reduced form
The 35mg dose was used throughout the 12-week treatment period
Oral MB was combined with topical PRP-FG repairing gel as a combinatorial therapeutic strategy
What This Means
This research suggests that combining a wound gel made from platelet-rich plasma and fibrin glue with a daily oral dose of methylene blue (a dye with known biological activity, taken in a special reduced form mixed into infant formula milk) may help heal diabetic foot ulcers that have not responded to standard treatments. In this very small pilot study of six patients, those who completed the 12-week treatment showed reduced wound size, better wound condition, and measurable improvements in oxygen levels reaching the skin tissue — a key factor in wound healing. Patients also reported feeling less pain, noticing less wound odor, and having less fluid draining from their wounds within just the first week of treatment, and no serious side effects were reported.
This research matters because diabetic foot ulcers that resist standard care are a serious and common problem, sometimes leading to amputation. The combination approach tested here targets the wound both locally (with the gel applied directly) and systemically (with the oral medication), which may address multiple barriers to healing at once. However, this study was very small — only four patients completed the full treatment — and was not a randomized controlled trial, meaning results should be interpreted cautiously. The authors themselves call for further, larger studies to confirm whether this approach is truly effective and safe before it could be considered for wider use.
Emadi E, Mousavian A, Saeed Modaghegh M, Alamdari D. (2026). Platelet-rich-fibrin repairing gel plus oral methylene blue for hard-to-heal diabetic foot ulcers: a pilot study.. Journal of wound care. https://doi.org/10.12968/jowc.2024.0387