Fish Skin Band-Aids: a natural way to speed wound healing

In this guest post, Mae Staples looks at how fish skin may hold the key to improved wound healing.

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Have a cut on your hand? You're apt to reach for the box of Band-Aids or roll of gauze in the medicine cabinet. But what about some fish skin protein to cover that wound? It may sound like a remedy straight out of The Little Mermaid, but, in fact, researchers in China have recently discovered that collagen obtained from Tilapia fish significantly speeds up wound healing in rats.

Even before Zhou et al. dove into the sea of wound healing, the use of collagen for promoting skin regeneration was well known. Collagen is one of the main structural proteins in connective tissues in the human body. Pig and cow collagen proteins have been used to promote wound healing successfully in the past, but the risk of introducing disease agents from these mammalian species inhibits broader applications in the medical field. And that's where fish skin swims in. Diseases and bacteria that affect fish are different from most human pathogens, and fish skin is also a cheap, readily available material for bandage production.

In considering the versatility of fish skin collagen, the researchers noted that the protein had excellent thermo-stability and tensile strength. This allows the bandage to adhere to the skin and adjust to body movements. Additionally, Tilapia collagen has been shown to promote the in vitro growth of keratinocytes, one of the two types of cells that are integral to skin wound healing and immune response. The second cell type is known as dermal fibroblasts. Migration of these cells to the wound site helps increase epithelial cell division, and dermal fibroblasts also secrete cytokine signals to promote wound healing.

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Zhou et al. began their experiment by extracting collagen from Tilapia skin with chemical purification methods. They then spun the protein into a nanofiber matrix, referred to as a collagen "sponge". Through structure analysis and gene sequencing, the researchers noted that the collagen had a high denaturation temperature and thus retained its unique triple helix shape even under environmental fluctuations. This data is promising for medical applications of the collagen based Band-Aids, as human skin can vary in temperature. A material that can adapt to different skin conditions and still stay in place is integral to bandage design.

Having established that the collagen matrix could stay put on the skin, Zhou et al. focused their attention on the immune response promoted by the foreign protein. In past studies, bovine collagen has caused hypersensitivity when applied to human skin, as well as increased antibody levels in some patients. The immune properties of Tilapia collagen had never been tested prior to this study.

The spleen is one of the largest immune organs in the human body and also contains B and T lymphocytes. These specialized immune cells recognize foreign antigens, or "invaders", and mediate a swift cellular response. Because of these immune properties, the researchers used spleen cell cultures from rats to test the immune response to Tilapia collagen. Their in vitro techniques showed that no noticeable immune response was invoked. The B and T lymphocytes remained at normal levels even with the addition of the collagen sponge.

With fish skin offering promising results in cell cultures, Zhou et al. next turned to live animal experiments. They wanted to see if a different immune response was produced in living organisms, as the bandages would be used on humans in a medical context. This allowed the researchers to study the degradation of the collagen sponge in live tissues to ensure no harmful small molecules innervated the wound as it healed.

IgG and IgM are two major antibodies in humoral immunity, or immunity mediated by macromolecules rather than cells. Collagen sponge was implanted into rat wounds, and levels of these antibodies were measured after twenty-eight days. No increase of the antibodies was observed. This signaled a high level of compatibility between the Tilapia bandage and the mammalian immune system. The ratio of CD4+ and CD8+ lymphocytes was also evaluated. Both categories of lymphocytes are important for antigen recognition and the elimination of infected cells. CD4+ lymphocytes also participate in signal transduction pathways in initiating other parts of the immune response. The ratio of these lymphocytes is a common clinical measure of coordinated cellular immunity. Rats injected with the Tilapia collagen showed a ratio similar to that of control groups without any fish skin bandages. Thus, both humoral and cellular mediated immunity remained at constant levels with collagen sponge additions. Importantly, rats with fish skin bandages also exhibited much faster wound healing than those treated with traditional bandage methods.

While fish skin bandages are a possibility for wound healing in the future, the researchers note that more work must be done before Tilapia collagen appears in your local drug store. Namely, tests on larger mammals must be carried out before human trials are feasible. The researchers are also looking to chemically alter the protein fibers in order to introduce antibacterial properties that safeguard against possible skin infection.

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Mae Staples is a recent graduate of Colgate University with a degree in Molecular Biology. She is interested in microbiology and biomedical research, and enjoys exploring the wonderful world of microbes through her scientific endeavors.

Refs

1) Zhou T, Wang N, Xue Y, et al. Development of Biomimetic Tilapia Collagen Nanofibers for Skin Regeneration through Inducing Keratinocytes Differentiation and Collagen Synthesis of Dermal Fibroblasts. ACS Appl. Mater. Interfaces 7: 3253-3262 (2015).

2) Pereira RF, Barrias CC, Granja PL, et al. Advanced biofabrication strategies for skin regeneration and repair. Nanomedicine 8(4): 603-621 (2013).

3) Kumar PS, Raj NM, Praveen G, et al. In vitro and in vivo evaluation of microporous chitosan hydrogel/nanofibrin composite bandage for skin tissue regeneration. Tissue Engineering Part A 19(3-4): 380-392 (2012).

4) Turley, Andrew. "Fish skin dressing helps heal wounds." Chemistry World. 18 Feb. 2015. Web.

Image credits
The Tilapia is free of copyright (Source: Dutch Fish Marketing Board). The keratinocyte image by ZEISS microscopy on Flickr Commons is distributed under a CC-BY-NC-ND license.