Picture learning to ride a bike on a warm summer’s day. The wind in your hair and sun on your skin. Suddenly, you hit a curb and scrape your knee on a sidewalk. Depending on how bad the scratch is, you may decide to place a bandage to help with the healing process. Having a variety of dressings available for use in compromised skin is practical for both those affected with injury and those performing the treatments. Many types of bandaging materials and surgical techniques exist in today’s medical toolkit. One interesting approach uses acellular fish skin (AFS) as a graft. While the odor of certain aquatic animals may turn people off, fish skins have significant potential as wound dressings.
Before touching on how AFS work, a brief overview of the healing process can be helpful. Wound healing duration and level of healing depends on the size and thickness of the wound, as well as any underlying comorbidities. Healing depends on three phases: inflammatory, proliferative, and maturation (1). The initial inflammatory phase, lasting 2-3 days, involves decreased blood flow and increased immune cell flow to the wound, aggregation of platelets and fibrin to the damaged tissue, and release of various pro-inflammatory molecules necessary in wound healing. The second phase, proliferative, begins around 7 days after the initial tissue damage. During this time, a bed of collagen is laid down to form the base of new tissue, new blood vessels are formed to divert resources to the wound site, and the periphery of the wound begins to contract. The final phase, maturation, occurs a few weeks later and can last up to one year. This step involves further contraction of the wound and formation of scar tissue. This is how tissues heal in a perfect environment. When damaged tissue is affected by underlying health issues such as diabetes mellitus, infection, contamination due to environment or lack of care, the healing process can be delayed or inhibited, requiring additional treatments and dressings for appropriate healing.
Many different types of wound dressing materials and techniques currently exist (2). Depending on the severity of the wound, the treatments can range from various types of topical dressings such as wet-to-dry bandages to a skin graft. Every treatment has its own benefits and drawbacks depending on the severity and environment of the wound (3). Topical wound treatments are generally cheap and commonly found, but also involve frequent bandage changes with possible caretaker involvement, and lifestyle changes depending on what environments the bandage could be compromised in. Additional forms of treatment used in more severe skin injuries include allografts and xenografts, or graphs used from different individuals of the same species and different species, respectively. While these tissues provide a replacement for damaged skin tissue, they are susceptible to limited sourcing, possible spread of disease, or rejection from the new host. Autographs, or skin graphs taken from the same person, are beneficial as they are directly taken from the same person and avoid disease transmission or rejection issues from allo- or xenographs. It may not be a possible treatment in instances where healing is already compromised, such as diabetic ulcers, or when significant areas of skin is lost or affected, such as severe burns. Situations such as these require a source material that includes a similar cellular infrastructure like humans, readily available, and provides a strong foundation for wound healing.
ASF, typically sourced from Nile Tilapia and Atlantic cod, makes an ideal dressing for a variety of reasons (4). Although this is a xenograft, transmission of disease from fish to humans is also significantly decreased due to the large evolutionary gap and distanced environments. Infectious organisms are found primarily in husbandry and can be removed with gentler detergents compared to the cleaning required for other xenographs (5,6). This reduced use of detergents allows for the preservation of the extracellular matrix and other substances provide further resources for the wound bed. The fish skin extracellular matrix, which is very porous, allows for a more efficient scaffold for host fibroblasts to lay down collagen in the wound bed. Anti-inflammatory substances such as omega-3 fatty acids, type I collage, and glucosamine are efficient speeding up the healing process and providing antimicrobial activity as well. In addition to the host healing process, ASF has been shown to need fewer dressing changes compared to other wound healing material (7), resulting in less burden on the patient and healthcare provider. Another important factor with ASF wound dressing involves shelf-life. Current biologic wound dressings such as cadavers and porcine tissue must be kept in preservatives prior to use, while ASF are stable at room temperature and are viable for 3 years (8). Not only does this reduce storage cost and material waste in the clinical setting, but this also allows for this material to be used in remote settings including military operations and wildlife medicine (9,10).
Acellular fish skin has a remarkable use for wound healing due to its structure and nutrient composition. Compared to bandage material such as gauze squares or occlusive dressings, fish skin requires less frequent dressings, reducing the need for material and use of healthcare staff providing the changes. Fish skin can also be easily sourced, has an insignificant effect on disease transmission, and has a long shelf-life. While not considered the “gold standard” for a variety of skin injuries (11), AFS offers multiple uses with real benefits.
Citations:
1. Wallace, H. A., Basehore, B. M., & Zito, P. M. (2023, June 12). Wound healing phases - statpearls - NCBI bookshelf. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK470443/
2. Fallah, N., Rasouli, M., & Amini, M. R. (2021, August 16). The current and advanced therapeutic modalities for Wound Healing Management. Journal of diabetes and metabolic disorders. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630293/
3. Ibrahim, M., Ayyoubi, H. S., Alkhairi, L. A., Tabbaa, H., Elkins, I., & Narvel, R. (2023, March 19). Fish skin grafts versus alternative wound dressings in wound care: A systematic review of the literature. Cureus. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10111873/#:~:text=Fish%20skin%20has%20shown%20anti,to%20alternative%20wound%20healing%20techniques.
4. Fiakos, G., Kuang, Z., & Lo, E. (2020, November 1). Improved skin regeneration with acellular fish skin grafts. Engineered Regeneration. https://www.sciencedirect.com/science/article/pii/S2666138120300116#bib0004
5. Prepared by Office of the Campus Veterinarian and the Office of Research Assurances. (2021). Zoonoses associated with fish. Zoonoses Associated with Fish | Institutional Animal Care and Use Committee | Washington State University. https://iacuc.wsu.edu/zoonoses-associated-with-fish/#:~:text=The%20zoonotic%20diseases%20associated%20with,Salmonella%2C%20Klebsiella%20and%20Streptococcus%20iniae.
6. Crapo, P. M., Gilbert, T. W., & Badylak, S. F. (2011, February 5). An overview of tissue and whole organ decellularization processes. Biomaterials. https://www.sciencedirect.com/science/article/abs/pii/S0142961211000895
7. Luze, H., Nischwitz, S. P., Smolle, C., Zrim, R., & Kamolz, L.-P. (2022, July 9). The use of acellular fish skin grafts in burn wound management-A systematic review. MDPI. https://www.mdpi.com/1648-9144/58/7/912
8. FAQ - Kerecis |. Kerecis. (2022a, March 29). https://www.kerecis.com/faq/#:~:text=Kerecis%C2%AE%20Omega3%20Wound%20is,be%20stored%20at%20room%20temperature.
9. Magnusson, S., Baldursson, B. T., Kjartansson, H., Rolfsson, O., & Sigurjonsson, G. F. (2017, March 1). Regenerative and Antibacterial Properties of Acellular Fish Skin Grafts and Human Amnion/Chorion Membrane: Implications for Tissue Preservation in Combat Casualty Care. OUP Academic. https://academic.oup.com/milmed/article/182/suppl_1/383/4209412?login=false
10. Quinton, A. (2023, April 20). Healing Burned Animals with Fish Skins. UC Davis. https://www.ucdavis.edu/health/news/healing-animals-with-fish-skins
11. Akilbekova, D., & Turlybekuly, A. (2023). Thickness skin graft. Thickness Skin Graft - an overview | ScienceDirect Topics. https://www.sciencedirect.com/topics/engineering/thickness-skin-graft#:~:text=A%20split%2Dthickness%20skin%20graft,%2C%20natural%20biomaterials%2C%20or%20hydrogels.