How Does Fish Skin Helps To Treat Wounds

  • Yue Qi Wang Master of Science - MS, Pharmacology, UCL

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Introduction

Importance of wound care

Wounds encompass any kind of disruption to normal and healthy anatomical and functional tissue. The damage extension might range from a simple break of epithelial tissue integrity to a deeper and more complex injury that can reach tissues under the skin and other structures such as vessels, ligaments, and bone. The origin of a wound is deeply knitted to its characteristics and physiology: acute wounds resulting from accidents or medical procedures can have complications leading to unusual healing progression or scarring.

On the other hand, chronic wounds derived from underlying diseases such as diabetes can lead to deep tissue damage like foot ulcers due to impaired wound healing.6 Properly caring for any kind of wound is pivotal for the well-being of the patient, as wounds with either early or late complications can impose significant morbidity that can lead to mortality. Poor wound care can cause a lot of pain, distress, anxiety, and even social isolation. Even though preventable, these effects of living with a wound, especially if not adequately cared for, can profoundly impact the quality of life of patients. 

Fish skin for wound treatment

To reduce the burden on individual patients and the healthcare system associated with wound care, scientists and healthcare professionals are delving into novel and more efficient therapeutic avenues. There is one innovative approach to wound care that recently emerged as, literally, a new layer of fish skin. An alternative to classic wound management techniques, the initially unconventional direct application of the skin from popular fish species like cod and tilapia to wounded areas has emerged as a potential revolution in the field of wound care.

The healing properties of fish skin

The use of fish skin grafts on wounds is an evidence-based strategy, especially in the case of individuals with serious cases of burns.3 Aimed mainly at preventing infections and promoting efficient healing of affected tissue, fish skin holds a promising set of properties that makes it a frontrunner in wound management. Hence, exploring the cellular and biochemical architecture of fish skin, alongside its biological properties, will grant a deeper understanding of its healing powers. 

Composition of fish skin

There are two components in fish skin that contribute greatly to its therapeutic benefits in wound care: collagen content and Omega-3 fatty acids. 

Collagen content

Collagen is a structural protein present in fish skin that gives tissues elasticity, strength, and resistance. A  collagen-constituted network provides a structural blueprint for cells to model and initiate the tissue-repairing process. The fish skin, abundant in collagen, aids wound closure and minimizes possible scarring by stimulating cell growth. 

Omega-3 Fatty Acids

Widely known for their anti-inflammatory features, Omega-3 fatty acids play a crucial role in reducing inflammation in wounded regions. By significantly curtailing inflammation, the Omega-3 content present in the skin of fish species creates a microenvironment ideal for tissue regeneration, expediting the healing process. 

Antibacterial properties

The interaction between fish and their underwater ecosystem has led to evolutionary processes specialising their skin in producing antibacterial compounds that form a protective shield against opportunistic microbes. These natural antimicrobial properties can also protect damaged tissue from potential infections that can lead to complications and hamper the healing course.1

Anti-inflammatory effects

Even as a necessary and natural response to tissue damage, the inflammation process can be dysregulated, resulting in delayed healing. The anti-inflammatory properties present in fish skin can accelerate the wound-healing process and significantly reduce pain and discomfort experienced by patients.

Promotion of tissue regeneration

Altogether, the features and properties of collagen and other bioactive molecules present in fish skin stimulate tissue regeneration by promoting the formation of young blood vessels and new skin tissue around the wounded area. In addition to a more dynamic healing process, fish skin can also reduce scarring, which can restore the appearance of healthy skin.

History of fish skin in wound healing and its modern rediscovery 

The practice of using fish skin as an aid for wound healing is not a recent discovery. Its origin is filled with historical significance, and it is directly associated with regions where this application has been rediscovered and improved in the last few years. 

The earliest reports of fish skin application for wound care are deeply rooted in traditional knowledge passed down generations from ancient civilizations. The immersion in the biodiversity and consequent abundance of fish experienced by indigenous communities living by water bodies, for instance, made the usage of fish skin an intuitive move towards better health management. Ancient Egyptians and indigenous from Asia, South America, and the Arctic, are representative groups that have historically developed this technique.

This historical context has lightened roads toward the resurgence of fish skin as a therapeutic ally in wound care in the contemporary medical landscape. Recent growing interest in harnessing natural and bioactive compounds has driven research to investigate fish skin constitution and properties. The modern rediscovery of the healing properties hidden in fish skin has resulted in the development of innovative wound dressings and grafts derived from fish skin as natural, sustainable, and effective options for addressing a wide range of wounds. 

Fish skin as a biological dressing

The process of preparing fish skin for medical use

The practical application of fish skin as a biological wound dressing is preceded by its careful preparation guided by a meticulous quality control process. This is to ensure the efficacy and safety of the fish skin in wound management. As a first step, the fish skin is washed, and any residual tissues are removed. 

This is followed by lyophilization, a process that removes residual liquid before sterilization by irradiation, the final step responsible for removing any remaining contaminants. Now properly prepared, the fish skin can be used as sheets, grafts, or even powder – this depends solely on the specificities of the targeted wound. The variety of possible applications makes fish skin a valuable resource for addressing wound care.

Advantages of using fish skin over traditional wound dressings

Fish skin, when prepared and utilized correctly, offers distinct advantages over traditional wound dressings, making it an appealing choice for healthcare providers and patients. Numerous clinical trials evaluating different aspects of fish skin have demonstrated the “biological band-aid” benefits due to the application of this approach:5,7,8,9

Reduced risk of infection

The intrinsic antimicrobial properties of fish skin create a barrier over the wound, protecting the wounded area against infections.1 Unlike traditional dressing options, fish skin not only shields the wounded tissue but also creates a safer microenvironment.

Enhanced wound healing 

The rich collagen proportion of collagen within fish skin enhances wound healing by promoting tissue repair and regeneration. A collagen-made structural support for cell growth allows faster skin repair and consequent wound healing and closure.5,8,9

Natural pain relief

More than aiding wound healing, the anti-inflammatory properties of fish skin also provide pain relief for patients.7,9 By mitigating inflammation that causes discomfort and can stall the healing progress, fish skin improves recovery rates.

Minimal Scarring

The active stimulation of tissue regeneration provided by fish skin leads to minimal scarring and consequent better cosmetic outcomes towards the final steps of wound closure.10

Clinical studies and case reports

Extensive clinical research and real-world case studies have played a crucial role in establishing the credibility and efficacy of fish skin as a biological dressing alternative in wound care.2 Patient experiences and specific conditions analyzed have proven fish skin to be a suitable therapeutic option.

Overview of clinical trials involving fish skin

Studies have shed light on the versatility of fish skin by examining its application as a dressing in diverse types of wounds, such as burns, surgical incisions, and ulcers. Altogether, the studies’ outcomes consistently point towards faster healing periods and improved patient comfort with fish skin usage. It is important to underscore the robustness of the investigative methods and peer-review analysis studying the value of fish skin in wound care. 

Safety considerations and potential side effects

Along with evaluating the benefits of fish skin application, clinical studies also addressed potential safety issues. While allergic reactions to fish skin can occur, they are considerably rare. Additionally, the sterilization that fish skin undergoes curtails infection risks. Even though severe side effects are very uncommon, patients should always be cautious and report any concerns or reactions to their medical professionals. 

Regulations and market

Regulatory approvals and guidelines for fish skin wound dressings

Regulatory agencies such as the Food and Drug Administration (FDA) in the United States and the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom supervise the approval process under rigorous regulations and monitor the clinical application of medical products, including fish skin biological dressings. 

Burn care and management are usually perceived as a high-cost and resource-intensive endeavour for optimal care. Confirming this scenario, a globally available tissue-regeneration technology for the treatment of chronic wounds, Kerecis® Omega3, is approved by the FDA but is still a not-so-viable option due to its elevated cost.3 

A research study conducted by Brazilian researchers has shown that treatment with tilapia skin led to a reduction in approximately 42% of the final treatment-related costs when compared to the traditional options.4 Even though studies on treatment-related costs are insufficient, analyzing the expansion of low-cost treatment options is vital, especially for low and middle-income nations, responsible for over 80% of burn injury reports worldwide. 

Future directions and research

Ongoing research and potential innovations

Ongoing research initiatives encompassing fish skin-based wound care range from optimizing preparation techniques to assessing novel applications and long-term outcomes. Other research avenues explore the combination of fish skin and other wound treatment technologies, such as growth factors for skin cells and stem cell therapies. Moreover, efforts towards the development of sustainable and cost-effective production of these fish skin dressings may drive an increase in the accessibility of this tool across the globe. 

Expanding the use of fish skin in different types of wounds

The versatility of fish skin-based dressings and their ability to adapt to different wound environments make them an asset in addressing a wide spectrum of clinical scenarios. As research progresses, we can anticipate a more comprehensive integration of fish skin into the wound care toolkit, offering improved outcomes for patients with diverse wound care needs, such as:5

  • Vaginal reconstruction
  • Treatment of burn injuries
  • Repair of the palate (roof of the mouth)

Summary

Wound care is not just about treating injuries; it includes infection prevention, tissue healing, and restoring functionality. Effective wound care contributes to better patient outcomes and eases the burden on healthcare systems. Fish skin, rich in collagen and omega-3 fatty acids, offers a natural solution for wound healing. 

Its antibacterial and anti-inflammatory properties, along with its tissue-regenerating abilities, underscore the compelling case for considering fish skin as a valuable resource in wound management. The versatility of fish skin holds promise for more comprehensive solutions for various wound types, from burns to chronic ulcers. With its natural properties and versatile applications, fish skin can redefine wound care methods, offering a holistic and sustainable solution that greatly benefits patients.

References

  1. Tiralongo F, Messina G, Lombardo BM, Longhitano L, Li Volti G, Tibullo D. Skin mucus of marine fish as a source for the development of antimicrobial agents. Front Mar Sci [Internet]. 2020 Sep 18 [cited 2023 Sep 22];7:541853. Available from: https://www.frontiersin.org/article/10.3389/fmars.2020.541853/full
  2. Ibrahim M, Ayyoubi HS, Alkhairi LA, Tabbaa H, Elkins I, Narvel R. Fish skin grafts versus alternative wound dressings in wound care: a systematic review of the literature. Cureus [Internet]. 2023 Mar 19 [cited 2023 Sep 22]; Available from: https://www.cureus.com/articles/144834-fish-skin-grafts-versus-alternative-wound-dressings-in-wound-care-a-systematic-review-of-the-literature
  3. Luze H, Nischwitz SP, Smolle C, Zrim R, Kamolz LP. The use of acellular fish skin grafts in burn wound management—a systematic review. Medicina [Internet]. 2022 Jul 9 [cited 2023 Sep 22];58(7):912. Available from: https://www.mdpi.com/1648-9144/58/7/912
  4. 300+ burn victims treated with tilapia skin in Ceará since 2016 - Agência UFC [Internet]. [cited 2023 Sep 22]. Available from: https://agencia.ufc.br/300-burn-victims-treated-with-tilapia-skin-in-ceara-since-2016/
  5. Lima Júnior EM, de Moraes Filho MO, Costa BA, Fechine FV, Vale ML, Diógenes AK de L, et al. Nile tilapia fish skin–based wound dressing improves pain and treatment-related costs of superficial partial-thickness burns: a phase iii randomized controlled trial. Plastic and Reconstructive Surgery [Internet]. 2021 May [cited 2023 Sep 22];147(5):1189. Available from: https://journals.lww.com/plasreconsurg/abstract/2021/05000/nile_tilapia_fish_skin_based_wound_dressing.27.aspx
  6. Spampinato SF, Caruso GI, De Pasquale R, Sortino MA, Merlo S. The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs. Pharmaceuticals (Basel). 2020;13(4):60. Published 2020 Apr 1. doi:10.3390/ph13040060
  7. Lima Júnior EM, de Moraes Filho MO, Costa BA, et al. A Randomized Comparison Study of Lyophilized Nile Tilapia Skin and Silver-Impregnated Sodium Carboxymethylcellulose for the Treatment of Superficial Partial-Thickness Burns. J Burn Care Res. 2021;42(1):41-48. doi:10.1093/jbcr/iraa099
  8. Yang CK, Polanco TO, Lantis JC 2nd. A Prospective, Postmarket, Compassionate Clinical Evaluation of a Novel Acellular Fish-skin Graft Which Contains Omega-3 Fatty Acids for the Closure of Hard-to-heal Lower Extremity Chronic Ulcers. Wounds. 2016;28(4):112-118.
  9. Edmar Maciel Lima Júnior, Manoel Odorico De Moraes Filho, Bruno Almeida Costa, Andréa Vieira Pontes Rohleder, Marina Becker Sales Rocha, Francisco Vagnaldo Fechine, Antonio Jorge Forte, Ana Paula Negreiros Nunes Alves, Francisco Raimundo Silva Júnior, Camila Barroso Martins, Mônica Beatriz Mathor, Maria Elisabete Amaral de Moraes, Innovative Burn Treatment Using Tilapia Skin as a Xenograft: A Phase II Randomized Controlled Trial, Journal of Burn Care & Research, Volume 41, Issue 3, May/June 2020, Pages 585–592, https://doi.org/10.1093/jbcr/irz205
  10. 10. Wallner C, Holtermann J, Drysch M, Schmidt S, Reinkemeier F, Wagner JM, Dadras M, Sogorski A, Houschyar KS, Becerikli M, et al. The Use of Intact Fish Skin as a Novel Treatment Method for Deep Dermal Burns Following Enzymatic Debridement: A Retrospective Case-Control Study. European Burn Journal. 2022; 3(1):43-55. https://doi.org/10.3390/ebj3010006

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PhD in Genetics and Molecular Biology – University of Campinas, Brazil

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