Acellular Fish Research Articles

Design of improved acellular fish skin as a promising scaffold for tissue regeneration applications

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.

The use of acellular fish skin grafts in burns and complex trauma wounds: a systematic review of clinical data

The use of acellular fish skin grafts in burns and complex trauma wounds: a systematic review of clinical data

Acellular Fish Skin Grafts for Treatment of Periocular Skin Defects.

To describe the outcomes of acellular fish skin grafts for repair of periocular anterior lamella skin defects after Mohs surgery for skin cancers. Following the institutional review board approval, we conducted a retrospective chart review of patients treated with acellular fish skin grafts between January 2022 and December 2023. Indication was to repair defects after Mohs excision of basal cell carcinoma and squamous cell carcinoma. Demographics, smoking and diabetes status, diagnosis, defect location, graft size, and complications were evaluated. Outcomes were analyzed using the scar cosmesis assessment and rating scale. Six patients (3 females and 3 males) with a mean age of 60.8 (range 44-80) had Mohs surgery for basal cell carcinoma (4) and squamous cell carcinoma (2). Location of defects included eyebrow (3 cases), lateral nasal wall (1 case), lower eyelid (1 case), and medial lower eyelid/nasal wall (1 case). Defect size ranged from 8 × 10 mm to 30 × 40 mm. Two patients had more than 1 application of xenograft. One patient developed a mild cicatricial ectropion. No other postoperative complications were seen, and all had good wound healing and cosmetically acceptable results. In this pilot study, acellular fish skin xenografts are shown to be promising skin graft substitutes in patients with Mohs defects and decrease the need for autologous skin harvesting or allogenic skin donation.

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.

The Use of Fish Skin Grafts in Children as a New Treatment of Deep Dermal Burns-Case Series with Follow-Up after 2 Years and Measurement of Elasticity as an Objective Scar Evaluation.

Background: Wound healing in deep dermal burn injuries continues to be a challenge in paediatrics. In the absence quick and spontaneous wound closure, split-thickness skin grafting is often necessary. Since the development of a new type of acellular fish matrix, which is very similar to the human skin matrix, skin closure and wound conditioning can be achieved without split-thickness skin grafting. Methods: The following study shows a case series of 20 children in whom a fish skin graft was used. The aim was to develop an algorithm for selecting and using fish skin and its long-term results after one and two years. Acellular fish skin worked as a granulation base for wound healing and also as a substitute for split-thickness skin grafts. Results: There was no evidence of infection. Skin transplants and, thus, additional operations could be avoided. The follow-up examinations showed an excellent result, both objectively by means of elasticity measurements (DermalabCombo®) and in the subjective assessment of the skin as part of the Patient and Observer Scar Assessment Scale (POSAS). Conclusion: Fish skin grafts are a good alternative to split-thickness skin grafts for deep dermal wounds. These results should be further analysed with a larger number of patients in future publications.

Influences of Polyphenols on the Properties of Crosslinked Acellular Fish Swim Bladders: Experiments and Molecular Dynamic Simulations.

Acellular fish swim bladders (AFSBs) are a promising biomaterial in tissue engineering, however, they may suffer from rapid degradation due to enzyme invasion. In this work, natural polyphenols, including epigallocatechin gallate (EGCG), proanthocyanidin (PC), tannic acid (TA) and protocatechuic acid (PCA), were utilized to improve the properties of AFSBs through crosslinking modifications. Fourier transform infrared (FTIR) results indicate that the triple helix of the collagen in AFSBs is well preserved after crosslinking. The differential scanning calorimetry (DSC), water contact angle (WCA) and in vitro degradation tests indicate that the polyphenol-crosslinked AFSBs exhibit improved thermal stability, enzymatic stability, hydrophilicity and mechanical properties. Among them, EGCG with multiple phenolic hydroxyl groups and low potential resistance is more favorable for the improvement of the mechanical properties and enzymatic stability of AFSBs, as well as their biocompatibility and integrity with the collagen triple helix. Moreover, the crosslinking mechanism was demonstrated to be due to the hydrogen bonds between polyphenols and AFSBs, and was affected by the molecular size, molecular weight and the hydroxyl groups activity of polyphenol molecules, as clarified by molecular dynamic (MD) simulations. The approach presented in this work paves a path for improving the properties of collagen materials.

Successful soft tissue reconstruction using acellular fish skin grafts in a secondary blast war injury.

Successful soft tissue reconstruction using acellular fish skin grafts in a secondary blast war injury.

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

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.

Radiological Evaluation Of Acellular Fish Swim Bladder and Autologous Bone Marrow Clot on Induced Radial Bone Defects in Rabbits

Radiological Evaluation Of Acellular Fish Swim Bladder and Autologous Bone Marrow Clot on Induced Radial Bone Defects in Rabbits

Fish Skin Grafts Affect Adenosine and Methionine Metabolism during Burn Wound Healing.

Burn wound healing is a complex process orchestrated through successive biochemical events that span from weeks to months depending on the depth of the wound. Here, we report an untargeted metabolomics discovery approach to capture metabolic changes during the healing of deep partial-thickness (DPT) and full-thickness (FT) burn wounds in a porcine burn wound model. The metabolic changes during healing could be described with six and seven distinct metabolic trajectories for DPT and FT wounds, respectively. Arginine and histidine metabolism were the most affected metabolic pathways during healing, irrespective of burn depth. Metabolic proxies for oxidative stress were different in the wound types, reaching maximum levels at day 14 in DPT burns but at day 7 in FT burns. We examined how acellular fish skin graft (AFSG) influences the wound metabolome compared to other standard-or-care burn wound treatments. We identified changes in metabolites within the methionine salvage pathway, specifically in DPT burn wounds that is novel to the understanding of the wound healing process. Furthermore, we found that AFSGs boost glutamate and adenosine in wounds that is of relevance given the importance of purinergic signaling in regulating oxidative stress and wound healing. Collectively, these results serve to define biomarkers of burn wound healing. These results conclusively contribute to the understanding of the multifactorial mechanism of the action of AFSG that has traditionally been attributed to its structural properties and omega-3 fatty acid content.

The Use of Acellular Fish Skin Grafts in Diabetic Foot Ulcers Management – a Systematic Review

Background: Diabetic foot ulcer (DFU) healing and management continue to be a major challenge for patients and healthcare providers, resulting in a considerable socio-economic burden. Lower-limb amputation is a severe clinical condition of DFU due to the presence of a chronic unresponsive diabetic foot ulcer with a high risk of infection, which raises morbidity and mortality rates. Rapid wound healing is necessary to prevent amputation. A recent advance in the development of applicable xenografts was acellular fish skin (AFS) grafts harvested from the North Atlantic cod (Gadus morhua) act as skin substitute, have a substantial lipid profile, primarily composed of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which have been shown to result in faster wound epithelialization, provide barrier protection against bacteria and alter the inflammatory profile of wounds. Due to these beneficial wound-healing properties, acellular fish skin might represent an effective treatment approach in chronic diabetic foot ulcer management. Methods: A systematic review of the literature up to July 2023 was conducted using the electronic databases PubMed, Google Scholar, and ScienceDirect. Titles and abstracts were screened for the following key terms (variably combined): "fish skin", "fish skin grafts", "acellular fish skin grafts", "Omega3 Wound matrix", "Diabetic foot ulcer", "Chronic ulcer", "wound healing". Results: The present study includes 12 trials that examined the effects of acellular fish skin grafts in diabetic foot ulcers. Compared to the standard of care, the use of acellular fish skin has been shown to accelerate wound healing resulting in reduced risk of amputation, reduced pain, reduced treatment-related costs, fewer dressing changes and improved quality of life. Conclusions: Acellular fish skin xenografts may represent an effective, low-cost treatment of chronic diabetic foot ulcers.

Acellular fish skin may be used to facilitate wound healing following wide surgical tumor excision in dogs: a prospective case series.

To prospectively evaluate clinical outcomes using acellular fish skin grafts (FSGs) for the management of complete wound healing by secondary intention after wide surgical excision of skin tumors in dogs. 5 dogs undergoing wide surgical excision of skin tumors on the distal extremity. FSGs were applied to surgical wound beds following wide excision of the tumor. Bandages were changed weekly and additional grafts placed when integration of the previous graft was complete. The wounds were assessed for the following: dimensions, tissue health (color), time to complete epithelialization, complications, and tumor recurrence. All masses were excised with 2-cm lateral margins and 1 fascial plane deep to the tumor. Tumor diagnoses included 3 mast cell tumors and 2 soft tissue sarcomas. Surgical wounds had a median area of 27.6 cm2 (range, 17.6 to 58.7 cm2). The median number of FSG applications was 5 (range, 4 to 9 applications). Complete epithelialization occurred within 7 to 9 weeks for uncomplicated wounds (3 of 5) and 12 to 15 weeks for complicated wounds (2 of 5) that sustained self-trauma. There were no adverse events related to the use of FSGs. Local recurrence was not seen over a follow-up period ranging from 239 to 856 days. Wide surgical excision of distal extremity skin tumors, followed by repeated application of acellular FSGs, resulted in complete healing of all wounds with no adverse events. This treatment method does not require advanced reconstructive surgical skills and may be useful for the management of skin tumors on the distal extremities.

Acellular Fish Skin for Tissue Replacement.

In modern practice, xenografts play a crucial role in wound management due to their regenerative properties. Of the various xenografts currently available on the market, acellular fish skin (AFS) grafts have emerged as a more effective alternative to existing xenografts and other standard of care (SOC) treatments for wound healing. Since AFS grafts require minimal processing, they maintain their structural integrity and natural properties, including an abundance of Omega-3 fatty acids, which is a distinctive, pro-regenerative feature. AFS grafts are also unique in that they are not derived from mammalian tissue, so there is no risk of viral transmission and no cultural or religious barriers to use. AFS grafts have been shown to be more cost-effective in the treatment of diabetic foot ulcers (DFUs) and result in a higher percentage of healed wounds, fewer amputations, and better patient quality of life. Several studies and case reports have highlighted the versatility of AFS in not only acute and chronic wound healing, but also for burn wound skin regeneration. Additionally, AFS may have promise as an implantable biologic matrix for suture line reinforcement in hernia repairs or breast and dura reconstruction.

Acellular Fish Skin Graft Use in Open Abdomen Management.

Open abdomen (OA) management post damage control laparotomy (DCL) is common in complex abdominal trauma and intra-abdominal catastrophe (IAC). Use of polyglactin 910 mesh (VICRYL™, Johnson & Johnson, New Brunswick, New Jersey) to cover the intra-abdominal contents and wound vacuum-assisted closure (VAC) is current practice in the management of temporary abdominal closure (TAC). This may have complications and requires two to three weeks for granulations to be ready for skin grafting. Acellular fish skin graft (AFSG; Kerecis™, Reykjavik, Iceland), use in wound care management has proven beneficial in the management of both chronic and acute wounds, such as burns, by increasing wound granulation. However, to our knowledge, its utility in OA management has not been reported. The objective of this report is to introduce a novel use of AFSG (Kerecis™) in open abdomen to decrease the time of TACs by accelerating formation of granulation tissue and placement of skin grafts in patients with post damage control laparotomy (DCL) for trauma and IAC when committed to open abdomen management is presented. Illustration of application of AFSG (Kerecis™) in two patients who underwent DCL for IAC and OA management is presented. Two patients with intra-abdominal catastrophe post-DCL and fistulae were enrolled; one with postoperative enteric fistula and the other with post-anastomotic ileo-colonic fistula breakdown and major intra-abdominal sepsis resulting in multiple organ system failure (MOSF). In both cases, a hostile abdomen was present. The application of AFSG accelerated the placement of skin grafts in both patients and decreased the use of wound VAC and hospital length of stay. This report illustrates the use of AFSG (Kerecis™) to accelerate placement of skin grafts in patients post-DCL and OA management. AFSG (Kerecis™) could be considered as part of the OA management strategy.

Fish Skin Graft: Narrative Review and First Application for Abdominal Wall Dehiscence in Children.

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.

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) graftsthat 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.

Acellular fish skin for wound healing.

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.

Aquaculture derived hybrid skin patches for wound healing

• The proposed patches are based on the derivatives of fish and crabs. • The acellular fish skin present porous surface for drug loading. • The patch owns brilliant biocompatibility, antibacterial and angiogenesis capability. • The proposed patches show effect on accelerating wound healing Natural biomaterials have been widely applied in wound treatment. Hotspots in this area are focused on reducing their immunogenicity and improving their therapeutic effect. In this work, we present a novel aquaculture derived hybrid skin patch based on acellular fish skin (AFS) and chitosan (CS) for wound healing. Such functional patch was simply constructed by infiltrating the vascular endothelial growth factor (VEGF)-loaded CS pregel into the porous scaffold of the AFS. As the natural molecules and structure of fish skin are well-retained during the synthesis processes, the final patch presented brilliant tensile property, water-absorption property, good biocompatibility and low immunogenicity. In addition, the integrated CS and VEGF endow the patch with antibacterial and angiogenesis capability respectively for promoting tissue growth and wound healing. Thus, in a full-thickness wound rat model, the hybrid patch has been demonstrated with dramatic therapeutic efficacy in inhibiting inflammatory, accelerating angiogenesis, collagen deposition, and tissue generation during the wound repair procedure. These features imply the practical value of this multifunctional aquaculture derived hybrid skin patch in clinical wound management. A novel aquaculture derived hybrid skin patch based on acellular fish skin (AFS) and chitosan (CS) for wound healing was presented. Such functional patch was simply constructed by infiltrating the vascular endothelial growth factor (VEGF)-loaded CS pregel into the porous scaffold of the AFS. The resultant patch owns brilliant tensile property, water-absorption property, good biocompatibility, antibacterial and angiogenesis capability. It is demonstrated that patches show effect on accelerating wound healing.

Preparation of extracellular matrix of fish swim bladders by decellularization with supercritical carbon dioxide

Fish swim bladders used to be considered as byproducts or waste in fishery; however, they are potential materials for biological medicine with abundant collagen. In this work, an efficient noncytotoxic decellularization process using sodium dodecyl sulfate (SDS) ternary system assisted with supercritical carbon dioxide (scCO2) as the green extraction fluid and ethanol (ET) as the cosolvent has been developed to harvest acellular fish swim bladders (AFSBs). The experimental results show that the tissue treated by SDS assisted with scCO2 and ethanol at 37 °C and 25 MPa can be decellularized thoroughly and maintains intact fibers and uniform pore distribution, which resulting in a tensile strength of 5.61 MPa and satisfactory biocompatibility. Meanwhile, the residual SDS content in scCO2/SDS/ET ternary system is 0.0122% which is significantly lower than it in scCO2/SDS system due to the enhanced mass transfer rate of SDS in tissues by scCO2 with ethanol. The synergy between SDS and ethanol can enhance the diffusion coefficient and the solubility of SDS in scCO2, which reduced the contact time between SDS and tissues. Meaningfully, the results obtained in this work can not only provide a novel strategy to produce acellular matrix with superior properties, but also offer a further understanding of the decellularization through scCO2 extraction processing with the synergy of suitable detergent/cosolvent.Graphical

Study on the preparation and properties of acellular matrix from the skin of silver carp (Hypophthalmichthys molitrix).

Acellular matrices are mainly composed of mammalian tissues, and aquatic tissues with lower biological risks and less religious restrictions are considered alternatives to mammalian tissues. The acellular fish skin matrix (AFSM) has been commercially available. Silver carp has the advantages of farmability, high yield and low price, but there are few studies on the silver carp acellular fish skin matrix (SC-AFSM). In this study, an acellular matrix with low DNA and endotoxin was prepared from the skin of silver carp. After treatment with trypsin/sodium dodecyl sulfate and Triton X-100 solutions, the DNA content in SC-AFSM reached 11.03 ± 0.85 ng/mg, and the endotoxin removal rate was 96.8%. The porosity of SC-AFSM was 79.64% ± 0.17%, which is favorable for cell infiltration and proliferation. The relative cell proliferation rate of SC-AFSM extract was 117.79% ± 15.26%. The wound healing experiment showed that SC-AFSM had no adverse acute pro-inflammatory response, which had a similar effect as commercial products in promoting tissue repair. Therefore, SC-AFSM has great application potential in biomaterials.