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Fish Skin Grafts: A Promising Treatment for Deep Diabetic Foot Ulcers?

29th Jan. 2025

The management of diabetic foot ulcers is a significant challenge, with amputation often being a necessary consequence. A novel approach using intact fish skin grafts, commonly used for burn wounds, has shown potential to improve healing outcomes, according to a recent international study.

As the largest organ in the body, the skin has a complex structure, making the search for an ideal replacement material particularly challenging. This impedes the management of diabetic foot ulcers, a serious complication of diabetes mellitus with a five-year mortality rate ranging from 13 % to 42 %. These ulcers often lead to serious infection and amputation, especially when they penetrate the bone or tendon.

Standard care—including vascular assessment, surgical debridement, appropriate dressings, infection management, and glycaemic control—has shown limited success. According to a review of 26 randomised controlled trials (RCTs), only 45 % of patients with diabetic foot ulcers achieve healing, with less than 40 % in severe cases. A recent international RCT evaluated the efficacy of intact fish skin graft against standard care in complex diabetic foot ulcers with exposed bone, joint or tendon, classified as grade 2 or 3 in the University of Texas diabetic wound classification system (UT). The results showed significant benefits in healing rates and time.

Accelerated healing with novel approach

The study involved 255 patients at 15 European centres in France, Germany, Italy, and Sweden. Participants were randomised 1:1 to receive either intact fish skin grafts or standard wound care. The graft, which was derived from Atlantic cod (Gadus morhua), was applied weekly for six weeks and then every two weeks. The primary endpoint was the proportion of ulcers achieving complete healing by 16 weeks, as assessed by clinical and photographic evaluation. Follow-up was extended to 24 weeks.

The results showed significant advantages for the fish skin graft intervention. At 16 weeks, 44 % of ulcers in the fish skin graft group achieved complete healing compared to 26.4 % in the standard care group (p < 0.001, odds ratio 2.55; 95 % CI 1.43–4.63). These figures increased to 55.2 % versus 37.8 % at week 24. In addition, ulcers healed faster in patients who received fish skin grafts, with a mean time to healing of 17.3 weeks versus 19.4 weeks for standard of care. Primary wound infections, the most common adverse event, occurred in 30.2 % of the fish skin graft group and 24.6 % of the standard care group.

Practical application of fish skin grafts

All patients underwent aggressive surgical wound debridement. After this, the intact fish skin graft was applied directly to the bleeding wound and covered with a secondary foam dressing in the intervention group. The dressing remained unchanged for at least 48 hours, and the graft was applied weekly for six weeks and then biweekly. The standard of care group received wound cleansing with isotonic saline, running water, and neutral soap, followed by the application of a suitable dressing.

“The use of intact fish skin grafts is similar to the use of sterile medical disposables. The matrix can be cut to the shape of the wound, and the nurses applying the matrix have received specific training in its use,” says Dardari, lead-author of the study. “The intact fish skin graft is widely used in the treatment of burns with significant results. Our team has also published its use in necrotising angiodermatitis.” Fish skin grafts have also been used in a military context due to their portability and cost-effectiveness. The fish skin grafts used in the trial were decellularised, lyophilised and supplied as sterile sheets.

Why fish skin grafts? A unique approach

Intact fish skin grafts have unique advantages due to their structure and biochemical properties. They act as a tissue-derived scaffold, promoting cellular and vascular infiltration as well as biologically active components involved in signal transduction and growth. “The intact fish skin graft is ecologically sustainable as well as rich in naturally occurring soluble molecules and omega-3 fatty acids,” explains Dardari. “Omega-3 fatty acids appear to have a variety of beneficial effects, including anti-inflammatory and, to some extent, antibacterial properties”. Due to the cold-water origin of Atlantic cod, it is particularly rich in omega-3 polyunsaturated fatty acids compared to tropical marine species. Also, fish skin in general carries minimal risk of transmitting viral or prion diseases unlike mammalian-derived skin products.

Overall, the results open up new avenues for the treatment of diabetic foot ulcers, particularly deep and penetrating wounds. According to the authors, further results of the study on patient satisfaction and cost effectiveness will be published in the future.

Key Points:
  • Diabetic foot ulcers are complex wounds with high morbidity and mortality rates.
  • The results of an international study support the use of intact fish skin grafts as biologically derived scaffolds known from managing chronic, complex wounds.
  • Fish skin grafts achieved 44 % healing at 16 weeks versus 26 % for standard of care in diabetic foot ulcers UT grade 2 or 3. Mean healing time was 17.3 weeks compared to 19.4 weeks for standard of care.
  • Intact fish skin grafts offer a unique combination of structural and biochemical advantages, including providing tissue-derived scaffolds and promoting wound healing and vascularisation..



Read Dured Dardari et al’s original article “Intact Fish Skin Graft to Treat Diabetic Foot Ulcers” here.


Author: Hanna Gabriel, BA MSc. Any opinions expressed in this article are the responsibility of EASD e-Learning.