The Role of Fish Skin Xenografts in Healing Complex Wounds: A Brief Case Report.

Non-healing wounds profoundly impact patient quality of life and present a significant financial burden. The Kerecis™ fish skin xenograft is a decellularized skin matrix that has been introduced to treat complicated wounds. The objective of this presentation is to highlight the use of fish skin xenograft in the treatment of a complex right flank wound with stool contamination, necrotizing soft tissue infection due to perforated colon cancer, and sepsis. This presentation follows the wound healing for 28 days following the operation and demonstrates the efficacy of fish skin xenografts in improved wound healing. A 61-year-old female with a past medical history of colon cancer and recent chemotherapy treatment presented with colon perforation causing right flank cellulitis and sepsis with necrotic abdominal wall tissue extending into the hip joint. She was taken for an emergent exploratory laparotomy, drainage of abdominal and retroperitoneal abscesses, open right hemicolectomy, diverting ileostomy, abdominal washout, intra-abdominal omental patch, placement of Strattice mesh, and debridement of necrotizing soft tissue infection of the right flank. After extensive debridement of her 15x10cmx5cm deep wound and placement of a Kerecis™ fish skin xenograft, the wound had completely healed with excellent granulation tissue, and the patient was scheduled for placement of a skin graft 28 days following the initial procedure. The results after xenograft application were outstanding, supporting the use of polyunsaturated fatty acid (PUFA) based xenografts in wound treatment due to their anti-inflammatory and angiogenic properties. This is definitely an option that needs to be considered in expediting the healing process for complex wounds.

Acellular fish skin grafts in the treatment of diabetic wounds: Advantages and clinical translation.

Diabetic wounds cannot undergo normal wound healing due to changes in the concentration of hyperglycemia in the body and soon evolve into chronic wounds causing amputation or even death of patients. Diabetic wounds directly affect the quality of patients and social medical management; thus researchers started to focus on skin transplantation technology. The acellular fish skin grafts (AFSGs) are derived from wild fish, which avoids the influence of human immune function and the spread of the virus through low-cost decellularization. AFSGs contain a large amount of collagen and omega-3 polyunsaturated fatty acids and they have an amazing effect on wound regeneration. However, after our search in major databases, we found that there were few research trials in this field, and only one was clinically approved. Therefore, we summarized the advantages of AFSGs and listed the problems faced in clinical use. The purpose of this paper is to enable researchers to better carry out original experiments at various stages.

Efficacy of acellular fish skin graft in the management of chronic ulcer: a systematic review and meta-analysis.

BACKGROUND: The wounds failing to heal through a timely and orderly standard of care (SOC) treatment are considered as chronic wounds, which add significant burden to healthcare systems around the world. SOC treatment has been commonly applied for management of chronic wounds, but SOC alone may not be adequate to heal all ulcers effectively. Fish skin graft (FSG) is a xenogenic skin substitute which could be used for accelerating skin healing. The current study was performed with the view of evaluating the effectiveness of FSG as an adjuvant treatment of SOC for chronic ulcer treatment. METHODS: Two authors independently searched the following electronic databases: PubMed, Embase, and CENTRAL, using keywords including "diabetic foot ulcer," "fish skin graft," and "wound healing." Clinical studies that evaluated the clinical outcomes of FSG in treatment of chronic ulcers were included in this meta-analysis. Random- or fixed-effect modeled meta-analyses were performed according to the heterogeneity test result (i.e., I2), to analyze the clinical outcome of FSG. RESULTS: A total of 8 studies were included in qualitative synthesis and meta-analysis, with 145 patients treated by SOC and 245 patients treated by SOC plus FSG. There was no significant difference between two groups for time to healing (MD = 1.99, 95% CI: -3.70~7.67, p = 0.493). The complete healing rate was significantly higher in FSG group compared with SOC alone (OR = 3.44, 95% CI: 2.03~5.82, p < 0.001***). Mean percentage area reduction (PAR) was reported in six studies, with a range of 71.6~97.3%. However, many of these studies did not report the value of standard deviation (SD), so we could not pool the data. No significantly different ulcer recurrence rate (RR = 0.60, 95% CI: 0.07~5.27, p = 0.645) and severe adverse events (SAEs) risk (RR = 1.67, 95% CI: 0.42~6.61, p = 0.467) were found between two groups. CONCLUSIONS: The application of FSG treatment for patients with chronic ulcers that do not respond well to SOC management could significantly increase the complete healing rate compared with SOC alone, without increased recurrence rate and SAEs risk.

Fish Skin Grafts Versus Alternative Wound Dressings in Wound Care: A Systematic Review of the Literature.

Wound healing poses a variety of challenges making it a vital subject in medicine. With the advancement of science, we have seen the use of a new xenograft known as acellular fish skin (AFS) grafts that are derived from either Atlantic cod or Nile Tilapia. Fish skin has shown anti-inflammatory and anti-bacterial properties that support and improve wound healing in a variety of wounds including burns and diabetic foot ulcers (DFU). There is ongoing research that evaluates the efficacy of fish skin grafts in comparison to alternative wound healing techniques. A literature search was conducted through the National Library of Medicine with search terms fish skin graft, AFS, xenograft, dehydrated human amnion/chorion, ulcer, burns, and wounds. A total of ten studies that investigate the efficacy of fish skin grafts either in comparison to a different wound healing technique or by simply observing wound healing with fish skin grafts and recording the results were chosen. AFS showed superior healing in comparison to collagen alginate dressings, silver sulfadiazine cream 1%, and allografts. Although there is no one specific gold standard technique for wound healing, fish skin grafts demonstrated overall improved and quicker wound healing, fewer dressing changes, less pain, and lower costs.

Intact Fish Skin Graft vs. Standard of Care in Patients with Neuroischaemic Diabetic Foot Ulcers (KereFish Study): An International, Multicentre, Double-Blind, Randomised, Controlled Trial Study Design and Rationale.

BACKGROUND: Cell and/or tissue-based wound care products have slowly advanced in the treatment of non-healing ulcers, however, few studies have evaluated the effectiveness of these devices in the management of severe diabetic foot ulcers. METHOD: This study (KereFish) is part of a multi-national, multi-centre, randomised, controlled clinical investigation (Odin) with patients suffering from deep diabetic wounds, allowing peripheral artery disease as evaluated by an ankle brachial index equal or higher than 0.6. The study has parallel treatment groups: Group 1 treatment with Kerecis® Omega3 Wound™ versus Group 2 treatment with standard of care. The primary objective is to test the hypothesis that a larger number of severe diabetic ulcers and amputation wounds, including those with moderate arterial disease, will heal in 16 weeks when treated with Kerecis® Omega3 Wound™ than with standard of care. CONCLUSION: This study has received the ethics committee approval of each participating country. Inclusion of participants began in March 2020 and ended in July 2022. The first results will be presented in March 2023. The study is registered in ClinicalTrials.gov as Identifier: NCT04537520.

Curing Necrotic Angiodermatitis with an Intact Fish Skin Graft in a Patient Living with Diabetes.

Background and Objectives: We describe a case of necrotic angiodermatitis. Materials and Methods: We used an intact fish skin graft to treat a patient living with diabetes, which was complicated by end-stage renal failure and arterial hypertension. The entire therapeutic procedure was carried out in ambulatory care without requiring the hospitalization of the patient. Results: The patient experienced a marked reduction in pain and complete epithelization of the lesion after 10 weeks of treatment. Conclusion: Our experience presents a new therapeutic approach to necrotic angiodermatitis.

Wound healing ability of acellular fish skin and bovine collagen grafts for split-thickness donor sites in burn patients: Characterization of acellular grafts and clinical application.

Due to its high polyunsaturated fatty acid content, acellular fish skin has emerged as a dermal substitute for the promotion of wound healing as it decreases scar formation while providing pain relief. However, various systematic studies on acellular fish skin, such as its biophysical analysis, in vitro activities, and clinical application, have not been sufficiently investigated. In this study, we conducted a comparative study to evaluate the wound-healing ability of acellular fish skin graft (Kerecis®) with that of the widely used bovine collagen skin graft (ProHeal®). The skin grafts were evaluated not only in terms of their biophysical properties, but also their in vitro cellular activities, using fibroblasts, keratinocytes, and human endothelial cells. The clinical study evaluated wound healing in 52 patients with acute burns who underwent skin grafting on donor sites from January 2019 to December 2020. The study was conducted with two groups; while only Kerecis® was tested in one group, Kerecis® and ProHeal® were compared in the other. In both groups, the application time of the dressing material was one to two days after split-thickness skin grafting to the donor sites. The Kerecis®-treatment group experienced faster healing than the other treatment group. In particular, the average wound healing time using the Kerecis® treatment and the ProHeal® treatment was 10.7 ± 1.5 days and 13.1 ± 1.4 days, respectively. We believe that the faster healing of the Kerecis® treatment, compared to that of the ProHeal® treatment, maybe due to the synergistic effect of the unique biophysical structure and the bioactive components of acellular fish skin.

Accelerated Wound Closure of Deep Partial Thickness Burns with Acellular Fish Skin Graft.

Thermal injuries are caused by exposure to a variety of sources, and split thickness skin grafts are the gold standard treatment for severe burns; however, they may be impossible when there is no donor skin available. Large total body surface area burns leave patients with limited donor site availability and create a need for treatments capable of achieving early and complete coverage that can also retain normal skin function. In this preclinical trial, two cellular and tissue based products (CTPs) are evaluated on twenty-four 5 × 5 deep partial thickness (DPT) burn wounds. Using appropriate pain control methods, DPT burn wounds were created on six anesthetized Yorkshire pigs. Wounds were excised one day post-burn and the bleeding wound beds were subsequently treated with omega-3-rich acellular fish skin graft (FSG) or fetal bovine dermis (FBD). FSG was reapplied after 7 days and wounds healed via secondary intentions. Digital images, non-invasive measurements, and punch biopsies were acquired during rechecks performed on days 7, 14, 21, 28, 45, and 60. Multiple qualitative measurements were also employed, including re-epithelialization, contraction rates, hydration, laser speckle, and trans-epidermal water loss (TEWL). Each treatment produced granulated tissue (GT) that would be receptive to skin grafts, if desired; however, the FSG induced GT 7 days earlier. FSG treatment resulted in faster re-epithelialization and reduced wound size at day 14 compared to FBD (50.2% vs. 23.5% and 93.1% vs. 106.7%, p < 0.005, respectively). No differences in TEWL measurements were observed. The FSG integrated into the wound bed quicker as evidenced by lower hydration values at day 21 (309.7 vs. 2500.4 µS, p < 0.05) and higher blood flow at day 14 (4.9 vs. 3.1 fold change increase over normal skin, p < 0.005). Here we show that FSG integrated faster without increased contraction, resulting in quicker wound closure without skin graft application which suggests FSG improved burn wound healing over FBD.

Acellular Fish Skin Grafts and Pig Urinary Bladder Matrix Assessed in the Collagen-Induced Arthritis Mouse Model.

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.