Purpose: Inadequate response to wound management is defined as a reduction in the wound area of <40-50% following four weeks of standard of care (SOC) and should be managed with a skin substitute product. We set out to evaluate a novel outcome-based model focusing on the management of hard-to-heal venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs) using SOC treatment or intact fish skin grafts (FSGs) in a regional hospital. Methods: We built an outcome-based model applying surrogate markers and endpoints of wound healing for VLU and DFU to determine the healing trajectory with SOC treatment. We could predict if VLU and DFU would heal by weeks 20 and 24, respectively, after four weeks of evaluating the initial wound area reduction. 51 patients were recruited (26 VLUs and 25 DFUs) and 42 wounds were randomized. 17 wounds deemed unlikely to heal by week 8 received management with FSG as per the Swiss Society for Dermatology and Venereology (SGDV) and the Swiss Association for Woundcare (SAfW) guidelines for the use of skin replacement products, and 26 wounds continued SOC for weeks 5-8. Results/Discussion: 12 wounds managed with FSG beat the modeled SOC healing predictions, with the majority healed >50% sooner and as early as <10% of the time than was predicted. Of these 17, five wounds failed to achieve the required size reduction in Week 4-8 (over 25% improvement in wound area vs. SOC). The FSG were assigned to treatment-resistant VLU and DFUs and were still able to heal these wounds most of the time and even changed the wound's healing trajectory that increased in size in the initial four weeks. Conclusion: This pilot study showed that management with FSG results in faster healing wounds than SOC predicted, while SOC-treated wounds mostly followed model predictions.

Diabetic foot ulcers (DFUs) represents a significant public health issue, with a rising global prevalence and severe potential complications including amputation. Traditional treatments often fall short due to various limitations such as high recurrence rates and extensive resource utilization. This editorial explores the innovative use of acellular fish skin grafts as a transformative approach in DFU management. Recent studies and a detailed case report highlight the efficacy of acellular fish skin grafts in accelerating wound closure, reducing dressing changes, and enhancing patient outcomes with a lower socio-economic burden. Despite their promise, challenges such as limited availability, patient acceptance, and the need for further research persist. Addressing these through more extensive randomized controlled trials and fostering a multidisciplinary treatment approach may optimize DFU care and reduce the global health burden associated with these complex wounds.

This study will explore the effectiveness of fish skin grafts (FSG) in ulcer healing in diabetic foot disease compared to standard of care (SOC).

The systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. The electronic databases of PubMed, EMBASE, and Web of Science (WoS) internet were searched for the outcome rate of complete ulcer healing. The risk of bias assessment was conducted using the tool recommended by the Cochrane Collaboration. Statistical analysis included the individual and combined result of the studies, heterogeneity test, the effect size, sensitivity analysis, and publication bias tests.

Five randomised controlled trials (RCTs) with a total of 411 patients were included in this study. This meta-analysis showed a higher rate of complete ulcer healing in groups receiving fish skin grafts (OR = 3.34, 95% CI 2.14-5.20, p < 0.01, I2 = 0%) compared to control groups.

Fish skin grafts have been shown to be more effective for achieving complete ulcer healing compared to current conventional treatments in diabetic foot disease.

Wound healing in the pediatric population is known to be a challenge and poorly studied. Split-thickness skin grafts, full-thickness skin grafts, and flaps overlap their applications with the growing field of cellular and tissue-based therapies. However, their role in pediatric reconstruction has yet to be defined. The Kerecis® Omega-3 wound patch, derived from decellularized codfish skin, has garnered attention due to its preserved microscopic architecture resembling the human extracellular matrix. This acellular dermal matrix acts as a scaffold, fostering dermal cell and capillary adhesion while harnessing omega-3 polyunsaturated fatty acids for granulation acceleration and antimicrobial effects. This study presents a comprehensive review and surgical protocol for utilizing Kerecis® fish skin in pediatric wound care. The research embraces a case series involving five patients with diverse wound locations. The Kerecis® Omega-3 wound patch underwent meticulous application and careful monitoring. The results highlight an average time of 48.6 days for complete epithelialization, yielding favorable outcomes with no hypertrophic scarring and mild retraction. Kerecis® fish skin grafting stands as a tool that not only accelerates healing but also addresses the multifaceted challenges associated with wound management in the pediatric population: the avoidance of donor site morbidity and improved postoperative pain control.

Marine long-chain omega-3 polyunsaturated fatty acids (ω3 FA) are involved in numerous cell responses and therefore vital for the mammal organism. Because of the attribution of immunomodulatory effects, a favourable impact on the inflammatory response in chronic wounds and cells involved in wound healing can be suspected. In the experimental setup, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were investigated regarding their impact on metabolic activity, cell proliferation and migration of human keratinocytes (HaCaT) and newborn foreskin fibroblasts (CRL-2522). For simulation of the microenvironment of a chronic wound, human chronic wound fluid (CWF) was used in the experimental setup addressing the in vitro influence of DHA, EPA and CWF on regenerative processes. The results showed a significant increase in the metabolic activity of keratinocytes and fibroblasts after 72 h treatment with DHA and EPA. In contrast, treatment with ω3 FA had no significant positive effect on skin cell proliferation. Both ω3 FA had no influence on in vitro wound closure. CWF demonstrated significantly adverse effects, which ω3 FA were unable to mitigate. It can be concluded that CWF exhibited the expected adverse effect on both skin cell types, especially inhibiting in vitro wound closure. ω3 FAs showed a slightly positive, yet rarely significant effect on human skin cells. Overall, the addition of DHA or EPA showed no relevant benefit for skin cells challenged with human CWF, merely in combination with DHA an initial significant increase in cell metabolism (fibroblasts) and cell proliferation (keratinocytes) could be observed.

A 3,480 g male neonate showed tachypnea symptom with a serum ionized calcium level of 0.66 mmol/L by routine clinical analysis. He was injected calcium gluconate intravenously through femoral vein catheter to treat the hypocalcemia. On second day after the injection, he started to show erythema in the flank area. The lesion became firm and changed into whitish crust consist of small crystals. Abdominal X-ray and ultrasonography showed the accumulation of calcium deposit in the subcutaneous layer of the lesion. Surgical debridement was performed to remove the crust with calcium deposit and acellular fish skin graft rich in omega-3 (Kerecis) was applied to the defect site for secondary intention of the defect wound. After 2 months, the skin and soft tissue defect were fully covered with healthy normal skin without depression or contracture. This report is a first case of iatrogenic calcinosis cutis without extravasation symptom.

Acellular Dermal Matrix (ADM) is mainly made with human or porcine skins and has the risk of zoonotic virus transmission. The fish skin-derived ADM could overcome the shortcoming. Fish skin acellular matrix has been used as wound dressing, but there is few systematic studies on tilapia-skin acellular dermal matrix (TS-ADM). In the present study, a novel TS-ADM was made by an alkaline decellularization process and γ-irradiation. The physical properties, biocompatibility, pre-clinical safety and wound healing activity of TS-ADM were systematically evaluated for its value as a functionally bioactive wound dressing. Histopathological analysis (hematoxylin and eosin staining, 4,6-diamidino-2-phenylindole (DAPI) staining) and DNA quantification both proved that the nuclear components of tilapia skin were removed sufficiently in TS-ADM. Compared to the commercial porcine acellular dermal matrix (DC-ADM), TS-ADM has distinctive features in morphology, thermal stability, degradability and water vapor transmission. TS-ADM was more readily degradable than DC-ADM in vitro and in vivo. In both rat and mini-pig skin wound healing experiments, TS-ADM was shown to significantly promote granulation growth, collagen deposition, angiogenesis and re-epithelialization, which may be attributed to the high expression of transforming growth factor-beta 1 (TGF-β1), alpha-smooth muscle actin (α-SMA) and CD31. Herein, the novel TS-ADM, used as a low-cost bioactive dressing, could form a microenvironment conducive to wound healing.

Chronic, nonhealing wounds consume a great deal of healthcare resources and are a major public health problem, associated with high morbidity and significant economic costs. Skin grafts are commonly used to facilitate wound closure. The grafts can come from the patient's own skin (autograft), a human donor (allograft), or from a different species (xenograft). A fish skin xenograft from cold-water fish (Atlantic cod, Gadus morhua) is a relatively recent option that shows promising preclinical and clinical results in wound healing. Chronic wounds vary greatly in etiology and nature, requiring large cohorts for effective comparison between therapeutic alternatives. In this study, we attempted to imitate the status of a freshly debrided chronic wound by creating acute full-thickness wounds, 4 mm in diameter, on healthy volunteers to compare two materials frequently used to treat chronic wounds: fish skin and dHACM. The purpose is to give an indication of the efficacy of the two therapeutic alternatives in the treatment of chronic wounds in a simple, standardized, randomized, controlled, double-blind study. All volunteers were given two identical punch biopsy wounds, one of which was treated with a fish skin graft and the other with dehydrated human amnion/chorion membrane allograft (dHACM). In the study, 170 wounds were treated (85 wounds per group). The primary endpoint was defined as time to heal (full epithelialization) by blinded assessment at days 14, 18, 21, 25, and 28. The superiority hypothesis was that the fish skin grafts would heal the wounds faster than the dHACM. To evaluate the superiority hypothesis, a mixed Cox proportional hazard model was used. Wounds treated with fish skin healed significantly faster (hazard ratio 2.37; 95% confidence interval: (1.75-3.22; p = 0.0014) compared with wounds treated with dHACM. The results show that acute biopsy wounds treated with fish skin grafts heal faster than wounds treated with dHACM.

To evaluate the potential benefit of an intact fish skin graft rich in omega-3 (Kerecis Omega3), in the management of postoperative diabetic foot wounds.

Prospective evaluation in eight patients with diabetes following forefoot surgery. The dressing was applied weekly for a period of six weeks in the diabetic foot clinic. At each visit the wound was photographed and independently measured using ImageJ software to calculate wound area. Secondary outcome measures were pain, infection, odour, discharge and irritation.

The wound area range was 0.94 to 29.55cm². In wounds of less than three months duration, regardless of size, the median percentage wound area reduction was over 84.9% at six weeks (n=6, range: 71.3 to 100%). There were two wounds over three months duration, in these the wound area reduction was <42% at six weeks (n=2, range: 41.2 to 41.1%). No patients developed infection or skin reactions. None reported odour, discharge or itching.

Our initial results demonstrate that the trend towards healing is more marked in wounds less than three months duration. This would suggest that the fish skin graft has potential to decrease time to healing in this patient group when used early on in the healing process, perhaps as a routine adjunct to postoperative diabetic foot wound management.

Postoperative diabetic foot wounds are difficult to heal. In this series, fish skin grafts show promise as an agent to accelerate wound healing. We suggest larger randomised trials to further evaluate its use in acute and chronic wounds.

Ten patients having split-thickness skin grafting for burn injury were treated with the fish skin xenografts.

There were no adverse reactions noted on the use of the fish skin grafts. No patient had any reaction to the fish skin and there was a zero incidence of infection. The handling of the fish skin was excellent, a robust and pliable xenograft that was easy to apply.The quality of donor site healing was judged to be good in all cases. Both the analgesic effect noted and the relatively short average times until 100% re-epithelialization are promising. We also illustrate two cases where the dressing was used to treat superficial burns.

It is vital that cellular- and tissue-based products (CTPs) used for wound treatment do not provoke autoimmunity. In this study, the immunogenic response to extracts of 2 CTPs of piscine and porcine origin was assessed in the collagen-induced arthritis model. Male DBA/1J mice were divided into 4 groups, each composed of 7 to 9 animals. Each animal was injected with one of following to assess their immune responses: (1) bovine type II collagen (100 µg) in Freund's adjuvant, (2) extract of piscine skin (100 µg) in Freund's adjuvant, (3) extract of porcine urinary bladder matrix (100 µg) in Freund's adjuvant, or (4) Freund's adjuvant alone (control) at the beginning of the experiment and 3 weeks later. Clinical signs of arthritis were assessed from week 5 onwards, and anti-type II and anti-type I collagen antibody immunoglobulin G (IgG) serum levels were measured before injections and 8 weeks after exposure using enzyme-linked immunosorbent assays. Only the mice exposed to bovine type II collagen developed clinical arthritis accompanied by very high anti-type II collagen IgG serum levels. Anti-type II collagen IgG serum levels were also detected in the porcine group but were undetectable in the piscine skin and control groups after 8 weeks. There were no significant differences in anti-type I collagen IgG serum levels among the groups. The results showed that piscine skin did not provoke systemic autoimmunity against type II collagens in DBA/1J mice.