Recent studies have shown that long-term scarring from burns is significantly reduced through the use of enzymatic debridement. Following enzymatic debridement of deep dermal burns, numerous wound dressings are available that provide an adequate wound environment and ideal conditions for rapid wound healing. In German burn centres, Suprathel® has mostly been used for this purpose. Since 2019, the alternative Kerecis Omega3 Wound®, which is derived from fish skin, has been used as an alternative in burn medicine. Therefore, we conducted a single-centre prospective, open, comparative, and intra-individual clinical study to gain initial experience in the use of Kerecis Omega3 Wound®, establish a treatment algorithm and compare Suprathel® and Kerecis Omega3 Wound® in the treatment of deep dermal burns after enzymatic debridement with respect to wound healing, exudation and pain. After enzymatic debridement of deep dermal burns of the hand and foot, wounds were divided into two areas: one was treated with Suprathel® and the other with Kerecis Omega3 Wound®. Dressing changes and wound checks were carried out on days 2, 4, 8, 12, 16, 24, and 48, after application. With this, initial experience concerning the handling of Kerecis Omega3 Wound® was gained and wound healing, infection, exudation, and pain were documented. In the period from January 1, 2022, to October 1, 2023, 22 patients between the ages of 18 and 83 years with deep dermal burns were treated. Satisfactory results were obtained in all cases; no patients had to undergo a second debridement followed by skin grafting. Mean healing time after the use of Kerecis Omega3 Wound was 17 days (min 8 days, max 25 days) whereas it was 23 days (min 12 days, max 42 days) in the Suprathel-Areas. No infections were observed in both groups. Exudation throughout the wound healing process was significantly higher in the Kerecis Omega3 Wound group than in the Suprathel group, whereas no significant differences in pain levels were documented. The management of dressing changes, the assessment of the progress of wound healing and adjusting the level of moisture in the dressings were obstacles, which could only be overcome by appropriate experience of the burn surgeon. In particular, adjusting the degree of moisture had a major influence on the progress of wound healing. Depending on these parameters, very different healing processes of the fish skin, from early dissolution into the so-called "active slough", to the drying out of the wound dressing to form a crust and remaining there for several weeks. In all 22 patients, however, the treatment led to spontaneous wound healing and satisfactory results without the need of skin grafting or other surgical procedures. Kerecis Omega3 Wound® is safe to use and suitable for the treatment of deep dermal burn wounds following enzymatic debridement. Its application leads to accelerated wound healing compared to the use of Suprathel®, however, owing to the different courses of the external appearance of the wound during wound healing, a high degree of user experience is necessary. Kerecis Omega3 Wound® might be useful to improve scarring after enzymatically debrided deep dermal burn wounds. Thus, a comparison between Kerecis Omega3 Wound® and Suprathel® concerning their long-term results is still pending.

Over the past few years, treatment of burn injuries has evolved beyond primary surgical therapy with the development of enzymatic debridement and new types of skin replacement materials by providing complex personalized therapy concepts aimed at preserving and replacing the dermal layer of the skin. The aim of our study was to develop an individualized treatment algorithm for mixed depth burn wound and evaluate the outcomes of individualized combined treatment of mixed depth burn wounds with enzymatic debridement and decellularized fish skin. A total of 18 patients with a mean age of 34.8 years and mean follow-up of 447.6 days were included. The mean total burn surface area was 12.3%. All patients received enzymatic debridement and an average area of 247.2 cm2 of decellularized fish skin. Days until complete epithelization were 49.4 ± 25.79 days. No patient developed scar contracture or keloid. The Patient and Observer Scar Assessment Scale (POSAS) observer scale showed an overall impression average of 2.2 ± 0.83. The POSAS patient scale showed an overall impression average 2 ± 0.7. The Vancouver Scar Scale showed an average score of 1.89 ± 1.45. In conclusion, combined treatment using enzymatic debridement and decellularized fish skin, polylactide membrane, or split skin grafts allows for a more individualized therapy for mixed depth burn wounds. Fish skin was found to provide a satisfying result in terms of the overall outcome of the developed scar tissue and could lead to a reduction in the area that requires autologous transplantation.

Background Managing diabetic foot ulcers (DFUs) is challenging due to poor blood supply, which leads to chronic wounds, increased susceptibility to infections, ischemia, and necrosis. The compromised quality of surrounding tissues, combined with complex underlying conditions and weakened immune systems, often hinders proper wound healing. Fish skin acellular dermal matrix (ADM) has emerged as an effective treatment option to promote healing in such wounds. Objective This study is the first to explore the use of fish skin ADM combined with negative pressure wound therapy (NPWT) for treating DFUs in the Asian population. The aim is to demonstrate the efficacy and effectiveness of this combined treatment approach. Methods Six patients with DFUs who visited the vascular surgery department between November 2022 and June 2023 were included in the study. Their wounds were treated with Kerecis® Omega3 Wound dressing for definitive closure, while NPWT was applied as an adjunct therapy to enhance graft uptake when suitable. Results The average initial wound size was 34.30 cm², with a complete healing rate of 100% achieved over an average of 19 weeks using Kerecis® Omega3 Wound dressing and adjunct NPWT. By the 12-week mark, the average reduction in wound size was 80.50%. Conclusions Fish skin ADM offers a biocompatible and sustainable solution for improving wound healing in difficult-to-treat DFUs. The addition of NPWT appears to enhance graft uptake, shorten the time to complete wound closure, and lower the risk of infections commonly associated with chronic diabetic foot wounds.

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.

Diabetic foot ulcers (DFUs) are a real public health problem which carry a high risk of amputation. The treatment of DFUs is based on general management such as the treatment of infection, arterial disease, and offloading, but recent studies have shown that the quality of the local covering can impact the healing rate.

We report the case of a 39-year-old man, living with diabetes since the age of 15, who developed DFU on the dorsum of his left foot, with muscle and tendon involvement. Conventional management with intensive diabetes control, surgery, treatment of infection and negative pressure therapy gave only limited results. The patient benefited from the application of an intact fish skin graft with complete epithelialisation of the ulcer after 10 weeks of treatment.

The use of intact fish skin graft appears to be a promising option for deep DFUs.

Complex and chronic lower extremity defects present a surgical challenge and can progress to eventual amputation if closure is not achieved. In addition to morbidity and mortality, these defects have a significant impact on patient quality of life and represent a substantial cost burden to the healthcare system. Ovine forestomach matrix (OFM) grafts are an advanced tissue scaffold option to supplement the surgical reconstruction ladder and may augment limb preservation in cases of complex lower extremity defects.

A prospective observational study enrolled 130 complex lower extremity reconstructions that received OFM as part of surgical management. Granulation tissue formation, defect closure, and postoperative complications were assessed up to 1 year postoperatively to evaluate the outcome of OFM grafts for limb salvage via surgical reconstruction.

Participant demographics and defect characteristics were reflective of a real-world inpatient population with complex and chronic defects. Despite complexity of the defects, no postoperative infections or major amputations were reported. The median time to complete granulation tissue coverage and fill was 30.0 days (95% confidence interval, 26.9-33.1) and the median time to complete defect closure was 127.0 days (95% confidence interval, 110.5-143.5). At 180 days, a 62% incidence of healing was achieved with a median product application of 1.0 (interquartile range, 1.0-1.0).

OFM-based grafts supported successful coverage of lower extremity defects in a real-world cohort with known risk-factors for amputation. Achieving successful closure with minimal complications, and often in a single application, suggests utility of OFM as a cost-effective adjunct in lower extremity reconstruction.

Decellularized marine tissues have been regarded as a desirable biomaterial because of their biological risk reduction, less religious constraints, and resemblance to mammalian tissues. The properties of these matrices can be improved by adding cross-linkers. In this study, after decellularization of the of Tilapia and Grass carp fish skin, a comparative study was conducted between them. Due to the higher abundance of collagen and glycosaminoglycans (GAGs) in Tilapia skin, it was selected for further study. In the next step, the cross-linking process was performed with three concentrations of 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/ N-Hydroxysuccinimide (EDC/NHS) and tannic acid cross-linkers. The MTT results showed that the cross-linked samples with low concentrations of EDC/NHS had higher biocompatibility compared to the cross-linked sample with high concentration of EDC/NHS, as well as all samples cross-linked with tannic acid. Mechanical and physical studies conducted on the skin of Tilapia fish showed that the 15 mM/7.5 mM concentration of EDC/NHS increased the mechanical and temperature strength and decreased the degradability and it did not influence cell attachment. In general, it was shown that different fish skins differ in terms of collagen and GAGs, and the optimal concentration of EDC cross-linker improves the mechanical and physical properties of the matrix derived from fish skin.

Decellularization is the process of obtaining acellular tissues with low immunogenic cellular components from animals or plants while maximizing the retention of the native extracellular matrix structure, mechanical integrity and bioactivity. The decellularized tissue obtained through the tissue decellularization technique retains the structure and bioactive components of its native tissue; it not only exhibits comparatively strong mechanical properties, low immunogenicity and good biocompatibility but also stimulates in situ neovascularization at the implantation site and regulates the polarization process of recruited macrophages, thereby promoting the regeneration of damaged tissue. Consequently, many commercial products have been developed as promising therapeutic strategies for the treatment of different tissue defects and lesions, such as wounds, dura, bone and cartilage defects, nerve injuries, myocardial infarction, urethral strictures, corneal blindness and other orthopedic applications. Recently, there has been a growing interest in the decellularization of fish tissues because of the abundance of sources, less religious constraints and risks of zoonosis transmission between mammals. In this review, we provide a complete overview of the state-of-the-art decellularization of fish tissues, including the organs and methods used to prepare acellular tissues. We enumerated common decellularized fish tissues from various fish organs, such as skin, scale, bladder, cartilage, heart and brain, and elaborated their different processing methods and tissue engineering applications. Furthermore, we presented the perspectives of (i) the future development direction of fish tissue decellularization technology, (ii) expanding the sources of decellularized tissue and (iii) innovating decellularized tissue bio-inks for 3D bioprinting to unleash the great potential of decellularized tissue in tissue engineering and regenerative medicine applications.

This case report explores the application of the KerecisTM fish skin xenograft, derived from North Atlantic Cod, in treating a large full-thickness wound resulting from necrotizing fasciitis (NF). A 41-year-old female with multiple comorbidities presented with NF of the dorsal forearm and hand. Initially managed with serial washouts with extensive debridement, the remaining dorsal forearm full-thickness wound with exposed tendons was treated with an application of the KerecisTM xenograft. The graft facilitated healing, evidenced by rapid epithelialization and decreased pain without the use of additional skin grafting. Traditionally used for chronic conditions, the use of KerecisTM in this acute, complex wound highlights its potential for integrating into human tissue and modulating inflammation, as well as acting as an antimicrobial barrier. This case underscores the need for further research into the effectiveness of fish skin xenografts in acute and complex wounds, suggesting a potential shift in emergency wound care practices.

Endovascular treatment of the common femoral artery (CFA) and its branches is often challenging. Sometimes, stent placement cannot be avoided. Furthermore, stent placement in this area carries several risks for complications. We present a challenging case in which we used a rotational atherectomy device percutaneously in cross-over-technique to recanalize the external iliac artery in combination with the femoral bifurcation, all in one session - and - without the need for a femoral stent in a multimorbid patient. We also tried to gain more insights in the patient's perspective and we took a validated health status evaluation into account.

The patient was presented due to chronic open wounds on the left foot for months (Stadium Fontaine IV). Duplex sonography and CT angiography showed a complete occlusion of the left external iliac artery with involvement of the left common femoral artery. Due to the pre-existing chronic diseases and the high risk of prolonged anesthesia, the patient was not suitable for open reconstruction of the common femoral artery. We aimed for endovascular therapy using a crossover maneuver to minimize anesthesia time as much as possible. The percutaneous treatment was performed with a rotational atherectomy device and drug-coated balloon angioplasty with satisfying angiographic results and complete blood-flow restoration. No peri-procedural complications occurred. We gained experience with this endovascular-treatment-device in our teaching hospital and more difficult cases can now be treated. The patient's perspective and health status were assessed during follow-up visit.

The endovascular treatment of severe calcifications in peripheral arterial occlusive disease (PAOD) seems to be a good solution for selected patients, significantly minimizing surgical trauma. The newly combined rotational atherectomy and thrombectomy devices have demonstrated positive outcomes in areas where conventional treatment has traditionally been the standard. The groin types of peripheral arterial occlusive disease (PAOD) are quite often challenging to operate. Open treatment of the common femoral artery has been the standard procedure until modern endovascular possibilities provide a new concept in this treatment, emphasizing a minimal invasive approach in multi morbid patients. The case description results in an illustrated follow up period of 6 months and is presented in line with the recommendations of the consensus-based surgical case reporting guideline development.

Managing peripheral arterial occlusive disease in the groin region poses a continual challenge. Traditionally, open treatment of the common femoral artery has been - and is - the established procedure. However, contemporary endovascular options now introduce a new paradigm in this treatment, highlighting minimally invasive approaches in multi morbid patients and its patient satisfaction.

Hydrogels have several characteristics, including biocompatibility, physical similarity with the skin's extracellular matrix, and regeneration capacity. Cell migration and proliferation are facilitated by natural polymers such as gelatin (Gel) and carboxymethyl cellulose (CMC). Gelatin dressing acts as a structural framework for cell migration into the wound area, stimulating cell division and promoting granulation tissue formation. Omega-3 fatty acids from fish oil may prevent wound infection and improve the healing of wounds in the early stages. We studied the preparation of wound dressing containing Omega-3 and its ability to heal wounds. In this study, CMC-Gel hydrogels containing different concentrations of Omega-3 were investigated in full-thickness wounds. After the fabrication of the hydrogels by using surfactant (tween 20) and microemulsion method (oil in water), various tests such as SEM, Water uptake evaluation, weight loss, cell viability, blood compatibility, and in vivo study in rat cutaneous modeling during 14 days were performed to evaluate the properties of the fabricated hydrogels. The analysis of the hydrogels revealed that they possess porous structures with interconnected pores, with an average size of 83.23 ± 6.43 μm. The hydrogels exhibited a swelling capacity of up to 60% of their initial weight within 24 h, as indicated by the weight loss and swelling measurements. Cell viability study with the MTT technique showed that no cytotoxicity was observed at the recommended dosage, however, increasing the amount of omega-3 caused hemolysis, cell death, and inhibition of coagulation activity. An in vivo study in adult male rats with a full-thickness model showed greater than 91% improvement of the primary wound region after 2 weeks of treatment. Histological analysis demonstrated Omega-3 in hydrogels, which is a promising approach for topical skin treatment to prevent scar, and has shown efficacy as wound dressing by improving the repair process at the defect site.

Bacterial nanocellulose (BNC) is a durable, flexible, and dynamic biomaterial capable of serving a wide variety of fields, sectors, and applications within biotechnology, healthcare, electronics, agriculture, fashion, and others. BNC is produced spontaneously in carbohydrate-rich bacterial culture media, forming a cellulosic pellicle via a nanonetwork of fibrils extruded from certain genera. Herein, we demonstrate engineering BNC-based scaffolds with tunable physical and mechanical properties through postprocessing. Human skeletal muscle myoblasts (HSMMs) were cultured on these scaffolds, and in vitro electrical stimulation was applied to promote cellular function for tissue engineering applications. We compared physiologic maturation markers of human skeletal muscle myoblast development using a 2.5-dimensional culture paradigm in fabricated BNC scaffolds, compared to two-dimensional (2D) controls. We demonstrate that the culture of human skeletal muscle myoblasts on BNC scaffolds developed under electrical stimulation produced highly aligned, physiologic morphology of human skeletal muscle myofibers compared to unstimulated BNC and standard 2D culture. Furthermore, we compared an array of metrics to assess the BNC scaffold in a rigorous head-to-head study with commercially available, clinically approved matrices, Kerecis Omega3 Wound Matrix (Marigen) and Phoenix as well as a gelatin methacryloyl (GelMA) hydrogel. The BNC scaffold outcompeted industry standard matrices as well as a 20% GelMA hydrogel in durability and sustained the support of human skeletal muscle myoblasts in vitro. This work offers a robust demonstration of BNC scaffold cytocompatibility with human skeletal muscle cells and sets the basis for future work in healthcare, bioengineering, and medical implant technological development.

Here, we report about a patient with a full-thickness burn injury of the left lower extremity with approximately 8% of total BSA affected. Initial therapy consisted of necrosectomy and wound coverage with split-thickness graft. The patient developed a wound infection with Pseudomonas aeruginosa, resulting in the failure of the skin graft to achieve complete healing. The case was further complicated by the patient's concurrent presentation of anemia, characterized by a hematocrit level of 19.8% on 11th day after admission. Additionally, the patient refused acceptance of any blood transfusion, adding a significant layer of complexity to the management strategy. In summary, the patient's critical state required an immediate intervention. Due to the contraindication for a further surgical debridement and autograft, we changed the treatment strategy to a conservative approach. First, the wound was debrided employing maggot therapy 17 days after admission. Subsequently, free soft tissue coverage was accomplished using decellularized fish skin dressings on 45th day. This approach yielded satisfactory wound closure. Following an approximately 2-month hospitalization period (52nd day after admission), the patient was discharged with a stable wound condition, nearing complete healing.

Wound healing complications are not uncommon after genital gender-affirming surgery and can pose significant challenges for the reconstructive surgeon. Acellular tissue matrices are products that contain extracellular matrix compounds without living cells and are used to expedite and improve wound healing. Some of these products have been described for a variety of different indications in gender-affirming surgery.  In this paper, the authors present a review of the current literature on the use of acellular tissue matrices in gender-affirming surgery as well as the authors' institutional experience in using these products.

Chronic skin defects in the head, face and neck pose challenges for closure, especially after multiple surgeries or radiation therapy. We report the case of a woman in her 70s with a chronic occipital wound following squamous cell carcinoma resections, resulting in exposed skull bone. Despite various options, we successfully treated the 4 cm x 5 cm wound with a Kerecis fish skin graft (FSG), observing significant improvement within a week. The FSG promoted granulation tissue formation, enabling subsequent full-thickness skin grafting from the patient's groin. Complete wound closure was achieved within 2 weeks, indicating FSG's efficacy in complex wound management. Our experience highlights FSG's potential as a valuable tool in wound healing and reconstruction, particularly in challenging cases involving the head and neck.

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.

To evaluate the efficacy of treatment of hard-to-heal wounds of patients with ischaemia of the lower extremities, and compare an omega-3 wound matrix product (Kerecis, Iceland) with a standard dressing.

A single-centre, prospective, randomised, controlled clinical trial of patients with hard-to-heal wounds following three weeks of standard care was undertaken. The ischaemic condition of the wound was confirmed as a decreased transcutaneous oxygen pressure (TcPO2) of <40mmHg. After randomising patients into either a case (omega-3 dressing) or a control group (standard dressing), the weekly decrease in wound area over 12 weeks and the number of patients that achieved complete wound closure were compared between the two groups. Patients with a TcPO2 of ≤32mmHg were taken for further analysis of their wound in a severe ischaemic context.

A total of 28 patients were assigned to the case group and 22 patients to the control group. Over the course of 12 weeks, the wound area decreased more rapidly in the case group than the control group. Complete wound healing occurred in 82% of patients in the case group and 45% in the control group. Even in patients with a severe ischaemic wound with a TcPO2 value of <32 mmHg, wound area decreased more rapidly in the case group than the control group. The proportions of re-epithelialised area in the case and control groups were 80.24% and 57.44%, respectively.

Considering the more rapid decrease in wound area and complete healing ratio in the case group, application of a fish skin-derived matrix for treating lower-extremity hard-to-heal wounds, especially with impaired vascularity, would appear to be a good treatment option.

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.

Current fish collagen hemostasis for wound healing products is commonly obtained by electrospinning or artificial cross-linking fish collagen fibers which lacks mechanical properties, and biofunctions. Here, a new bio-active fish skin scaffold (FSS) is shown using in situ cross-linked scaleless freshwater fish skin adding adipose-derived stem cells (ASCs)-produced exosomes for hemostasis and wound healing. The structure, pore size, and the thickness of FSS is studied by swelling test, Fourier-transform infrared (FT-IR) spectra, scanning electron microscope (SEM) images, and histological analysis. The biofunctions of the FSS are also tested in vitro and in vivo. FSS keeps two functional layers: The dermis layer collagen forms a sponge like structure after swelling and in situ cross-linking treatments. The pore size of the FSS is ≈152 ± 23.54 µm, which is suitable for cells growing, angiogenesis and ASCs exosomes accelerate wound healing. The fat-rich epidermis layer can keep the wound moisty and clean before completely healed. In vitro and in vivo experimental results indicate that FSS+Exosomes enhances rat skin cavity wound healing. In situ sodium chloride cross-linked FSS+Exosomes provides a new strategy as functional hemostatic dressing scaffold for wound healing.

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.

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.

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.

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.

War-related burns are common injuries, also among the civilian population. Additional trauma such as fractures or shrapnel wounds may add significant morbidity. Burn injuries in war zones are furthermore frequently undertreated and hence prone to complications. We report a case of a young female victim of war, whose severely infected burn wounds could be successfully healed using a combination of targeted antimicrobial therapy, wound conditioning using decellularized fish skin, and subsequent skin grafting.

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.

As a natural material, fish skin contains significant amounts of collagen I and III, and due to its biocompatible nature, it can be used to regenerate various tissues and organs. To use fish skin, it is necessary to perform the decellularization process to avoid the immunological response of the host body. In the process of decellularization, it is crucial to conserve the extracellular matrix (ECM) three-dimensional (3D) structure. However, it is known that decellularization methods may also damage ECM strands arrangement and structure. Moreover, after decellularization, the post-processing of fish skin improves its mechanical and biological properties and preserves its 3D design and strength. Also, sterilization, which is one of the post-processing steps, is mandatory in pre-clinical and clinical settings. In this review paper, the fish skin decellularization methods performed and the various post-processes used to increase the performance of the skin have been studied. Moreover, multiple applications of acellular fish skin (AFS) and its extracted collagen have been reviewed.

Engineering cardiac patches are proven to be effective in myocardial infarction (MI) repair, but it is still a tricky problem in tissue engineering to construct a scaffold with good biocompatibility, suitable mechanical properties, and solid structure. Herein, decellularized fish skin matrix is utilized with good biocompatibility to prepare a flexible conductive cardiac patch through polymerization of polydopamine (PDA) and polypyrrole (PPy). Compared with single modification, the double modification strategy facilitated the efficiency of pyrrole polymerization, so that the patch conductivity is improved. According to the results of experiments in vivo and in vitro, the scaffold can promote the maturation and functionalization of cardiomyocytes (CMs). It can also reduce the inflammatory response, increase local microcirculation, and reconstruct the conductive microenvironment in infarcted myocardia, thus improving the cardiac function of MI rats. In addition, the excellent flexibility of the scaffold, which enables it to be implanted in vivo through "folding-delivering-re-stretehing" pathway, provides the possibility of microoperation under endoscope, which avoids the secondary damage to myocardium by traditional thoracotomy for implantation surgery.

Necrotizing fasciitis (NF) is a serious infectious disease that can initially place the patient's life in danger and, after successful surgical and antibiotic treatment, leaves extensive wounds with sometimes even exposed bones and tendons. Autologous skin grafts are not always possible or require adequate wound bed preparation. Novel intact fish skin grafts (iFSGs; Kerecis® Omega3 Wound, Kerecis hf, Isafjördur, Iceland) have already shown their potential to promote granulation in many other wound situations. Faster wound healing rates and better functional and cosmetic outcomes were observed due to their additionally postulated anti-inflammatory and analgesic properties. Therefore, iFSGs may also be essential in treating NF. We present our initial experience with iFSGs in treating leg wounds after NF and review the literature for the current spectrum of clinical use of iFSGs.

We present two male patients (aged 60 and 69 years) with chronic or acute postsurgical extensive leg ulcers six weeks and six days after necrotizing fasciitis, respectively. Both suffered from diabetes mellitus without vascular pathologies of the lower limbs. A single application of one pre-meshed (Kerecis® Graftguide) and one self-meshed 300 cm2 iFSG (Kerecis® Surgiclose) was performed in our operation room after extensive surgical debridement and single circles of negative wound pressure therapy. Application and handling were easy. An excellent wound granulation was observed, even in uncovered tibia bone and tendons, accompanied by pain relief in both patients. Neither complications nor allergic reactions occurred. The patients received autologous skin grafting with excellent functional and cosmetic outcomes.

iFSGs have the potential to play a significant role in the future treatment of NF due to the fast promotion of wound granulation and pain relief. Our experience may encourage surgeons to use iFSGs in NF patients, although high-quality, large-sized studies are still required to confirm these results. The observed effects of iFSGs on wounds associated with NF may be transferred to other wound etiologies as well.

Fish skin grafting as a new skin substitute is currently being used in clinical applications. Acceleration of the wound healing, lack of disease transmission, and low cost of the production process can introduce fish skin as a potential alternative to other grafts. An appropriate decellularization process allows the design of 3D acellular scaffolds for skin regeneration without damaging the morphology and extracellular matrix content. Therefore, the role of decellularization processes is very important to maintain the properties of fish skin. In this review article, recent studies on various decellularization processes as well as biological, physical, and mechanical properties of fish skin and its applications with therapeutic effects in wound healing were investigated.

Acellular fish skin grafts (FSGs) are tissue-based products created by minimally processing the skin of the Atlantic cod (Gadus morhua). The FSG is rich in omega-3 and facilitates tissue regeneration by supporting revascularization and ingrowth in the proliferation and remodeling phases of wound healing. FSG is structurally more similar to human skin than antiviral-processed skin substitutes such as amniotic membrane, and there are no known prion, bacterial, or viral diseases that can be transmitted from North-Atlantic cod to humans. The FSG is processed using a proprietary method that preserves the structure and lipid composition of the skin. FSG is CE marked, and US Food and Drug Administration cleared for multiple clinical applications in partial and full-thickness wounds. FSG is currently the only acellular dermal matrix product that does not originate from mammalian tissues. For this narrative review, Medline and UpToDate were used to include a total of 21 articles published from 2015 to 2022 about fish skin graft use. We also reported a case of a 7-year-old boy who underwent treatment with FSG for abdominal wall dehiscence at our department of pediatric surgery, IRCCS Sant'Orsola-Malpighi, Alma Mater Studiorum, University of Bologna, University Hospital of Bologna. FSG provides a valuable and sustainable treatment that improves wound healing in both adult and pediatric populations. We described the first application of an FSG for wound dehiscence of the abdominal wall in a pediatric patient, reporting how FSG was completely reabsorbed and improved the skin's repair.

In this report, we present a 57-year-old man with chronic bilateral lower extremity wounds from nonuremic calciphylaxis, which were successfully reconstructed using a piscine-derived acellular dermal matrix. The acellular dermal matrix incorporated quickly, providing a wound bed that was amenable to skin grafting. We demonstrate that this is an effective off-the-shelf solution for these chronic wounds, resulting in pain reduction and complete closure of the wounds, allowing the patient to return to his previous baseline activities, and improving his quality of life.

The skin is one of the most essential organs in the human body, interacting with the external environment and shielding the body from diseases and excessive water loss. Thus, the loss of the integrity of large portions of the skin due to injury and illness may lead to significant disabilities and even death. Decellularized biomaterials derived from the extracellular matrix of tissues and organs are natural biomaterials with large quantities of bioactive macromolecules and peptides, which possess excellent physical structures and sophisticated biomolecules, and thus, promote wound healing and skin regeneration. Here, we highlighted the applications of decellularized materials in wound repair. First, the wound-healing process was reviewed. Second, we elucidated the mechanisms of several extracellular matrix constitutes in facilitating wound healing. Third, the major categories of decellularized materials in the treatment of cutaneous wounds in numerous preclinical models and over decades of clinical practice were elaborated. Finally, we discussed the current hurdles in the field and anticipated the future challenges and novel avenues for research on decellularized biomaterials-based wound treatment.

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.

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.

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.

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.

The optimal therapy for deep burn wounds is based on the early debridement of necrotic tissue followed by wound coverage to avoid a systemic inflammatory response and optimize scar-free healing. The outcomes are affected by available resources and underlying patient factors, which represent challenges in burn care and suboptimal outcomes. In this study, we aimed to determine optimal burn-wound management using enzymatic debridement (NexoBrid™, MediWound Germany GmbH, Rüsselsheim, Germany) and intact fish skin (Kerecis® Omega3 Wound, Isafjordur, Iceland).

In this retrospective case series, 12 patients with superficial or deep dermal burn wounds were treated with enzymatic debridement followed by fish skin, Suprathel® (PolyMedics Innovations GmbH, Denkendorf, Germany), or a split-thickness skin graft (STSG). Patients' outcomes regarding healing and scar quality were collected objectively and subjectively for 12 months after the burn injury.

Wounds treated with fish skin demonstrated accelerated wound healing, a significantly higher water-storage capacity, and better pain relief. Furthermore, improved functional and cosmetic outcomes, such as elasticity, skin thickness, and pigmentation, were demonstrated. The pain and itch expressed as POSAS scores (Patient and Observer Scar Assessment Scale) for fish skin decreased compared to those for wounds managed with an STSG or Suprathel. Importantly, fish skin-treated wounds had significantly improved sebum production and skin elasticity than those treated with Suprathel but showed no significant superiority compared to STSG-treated wounds.

Enzymatic debridement in combination with intact fish skin grafts resulted in the faster healing of burn wounds and better functional and aesthetic outcomes than split-thickness skin grafts and Suprathel treatment.

The use of acellular fish skin grafts (FSG) for the treatment of burn wounds is becoming more common due to its beneficial wound healing properties. In our previous study we demonstarted that FSG is a scaffold biomaterial that is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) conjugated to phosphatidylcholines. Here we investigated whether EPA and DHA derived lipid mediators are influenced during the healing of burn wounds treated with FSG. Deep partial and full thickness burn wounds (DPT and FT, respectively) were created on Yorkshire pigs (n = 4). DPT were treated with either FSG or fetal bovine dermis while FT were treated either with FSG or cadaver skin initially and followed by a split thickness skin graft. Punch biopsies were collected on days 7, 14, 21, 28 and 60 and analyzed in respect of changes to approximately 45 derivatives of EPA, DHA, arachidonic acid (AA), and linoleic acid (LA) employing UPLC-MS/MS methodology. Nine EPA and DHA lipid mediators, principally mono-hydroxylated derivatives such as 18-HEPE and 17-HDHA, were significantly higher on day 7 in the DPT when treated with FSG. A similar but non-significant trend was observed for the FT. The results suggest that the use of FSG in burn wound treatment can alter the formation of EPA and DHA mono hydroxylated lipid mediators in comparison to other grafts of mammalian origin. The differences observed during the first seven days after treatment indicates that FSG affects the early stages of wound healing.

To report the clinical outcomes of the use of acellular fish skin grafts (FSGs) for the management of complex soft tissue wounds of various etiologies in dogs and cats.

13 dogs and 4 cats with complex wounds treated with FSGs between February 2019 and March 2021.

Medical records were reviewed for information regarding cause, location, size of the wound, management techniques, complications, and clinical outcomes.

In dogs, the number of FSG applications ranged from 1 to 4 (median, 2 graft applications). The time between each application ranged from 4 to 21 days (median, 9.5 days). Time to application of the first FSG ranged from 9 to 210 days (median, 19 days). Wounds closed by second-intention healing following the first fish skin application between 26 and 145 days (median, 71 days; n = 12). In cats, 1 or 2 FSGs were used, and the wounds of 3 of 4 cats healed completely by secondary intention. The wounds of 1 dog and 1 cat did not heal. There were no adverse events attributed to the use of the FSGs.

For dogs and cats of the present study, complete healing of most wounds occurred with the use of FSGs, the application of which did not require special training, instruments, or bandage materials.

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.

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.

Acellular fish skin (ACS) has emerged as a dermal substitute used to promote wound healing with decreased scar formation and pain relief that may be due to polyunsaturated fatty acid (PUFA) content. However, the PUFA content of ACS is still unknown. The aim of this study was to compare the total fatty acids and lipid profiles of ACS to two bovine-based grafts and standard of care human cadaver skin (HCS). Furthermore, there was also the goal to assess the capability of ACS lipid content to enhance wound healing. The fatty acid analysis was performed with GC-FID, and an LC-MS untargeted method was developed in order to the analyse the lipid profiles of the grafts was. The enhancement of wound healing by the ACS extract was investigated in vitro on HaCat cells. Our results showed that ACS had the highest content of PUFA (27.0 ± 1.43% of their total fatty acids), followed by HCS (20.6 ± 3.9%). The two grafts of bovine origin presented insignificant PUFA amounts. The majority of the PUFAs found in ACS were omega-3, and in HCS, they were omega-6. The untargeted lipidomics analysis demonstrated that ACS grafts were characterized by phosphatidylcholine containing either 20:5 or 22:6 omega-3 PUFA. The ACS lipid extract increased the HaCat cells migration and enhanced wound closure 4 hr earlier versus control. Our study demonstrated that ACS has a lipid profile that is distinct from other wound healing grafts, that PUFAs are maintained in ACS post-processing as phosphatidylcholine, and that ACS lipid content influences wound healing properties.

Herpetic infections caused by Herpes simplex virus (HSV) are among the most common human infections, affecting more than two quarters of the world's population. The standard treatment for orofacial herpes is the administration of antiviral drugs, mainly acyclovir (ACV). However, current products are mostly based on semisolid formulations that have limited ability to promote drug skin penetration and tend to leak from the application site, thus showing reduced ability to sustain local drug residence. This work reports on the production of poly (ε-caprolactone) (PCL) fibrous matrices with ACV and omega-3 fatty acids (ω3) for application as dressings to the topical treatment of orofacial herpes. PCL fibrous matrices with the co-incorporated bioactive compounds were obtained by electrospinning and characterized regarding their morphology, chemical, physical, and mechanical properties. The potential use of the developed polymeric fibrous matrices for topical applications was evaluated by: (i) the release kinetics of the bioactive compounds; (ii) the occlusive factor of the fibrous mat; (iii) ACV skin permeation capacity; and (iv) the cytotoxicity in a keratinocyte cell line. PCL fibrous matrices loaded with the bioactive compounds presented a smooth morphology and a good balance between flexibility and hardness essential to be durable for handling, while having a desirable texture to be used comfortably. The fibrous mat also provided a sustained release of ACV during 96 h and improved the skin permeability of this drug (Kp = 0.00928 ± 0.000867 cm/h) presenting also high porosity (74%) and a water vapor transmission rate (WVTR) of 881 ± 91 g/m²day, essential to maintain moist and oxygen for faster healing of herpes lesions. Furthermore, cytotoxicity studies suggest that the fibrous mat are safe for topical application. Overall, the PCL based electrospun fibrous matrices with ACV and ω3 hereby described have the potential to be used as therapeutic bandage systems for the treatment of orofacial herpes.