Have a cut on your hand? You’re most likely 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.
“Tilapia” by Nederlands Visbureau. Available from: Flickr Commons, https://www.flickr.com/search/?sort=relevance&text=tilapia (accessed March 8, 2015).
Even before the Zhou et al. dove into the sea world of wound healing, the use of collagen for promoting skin regeneration was well established. 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 very different from most human pathogens, and fish skin is also an abundant and cheap 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 growth of keratinocytes in vitro. Keratinocytes are one of 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 the cells to the wound site helps increase epithelial cell division and dermal fibroblasts also secrete cytokine signals to promote wound healing.
“Skin cell (keratinocyte)” by ZEISS Microscopy. Available from: Flickr Commons, https://www.flickr.com/search/?q=immune%20cells (accessed March 8, 2015).
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.
Once establishing that the collagen sponge could stay put on the skin, Zhou et al. focused their attention on the immune response the foreign protein promoted. In past studies, bovine collagen has caused hypersensitivity when applied to human skin and even increased levels of antibodies 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 the 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 the original organism state, as the bandages would be used on humans in a medical context. The rats also 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.
Two major antibodies in humoral immunity, or immunity mediated by macromolecules as opposed to cells, include IgG and IgM. When the collagen sponge was implanted into rat wounds, the antibodies were detected after twenty-eight days. No increased level of the antibodies was observed. This signaled a high level of compatibility between the Tilapia bandage and the mammalian immune system. Additionally, the ratio of CD4+ and CD8+ lymphocytes was evaluated. Both categories of lymphocytes are important for antigen recognition and elimination of infected cells. CD4+ lymphocytes also participate in signal transduction pathways to initiate other parts of the body’s 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 definitely a possibility for wound healing in the future, the researchers note that more work must be carried out before Tilapia collagen appears in your local drug store. Namely, tests on larger animals must be carried out, and the protein fibers should be modified to present additional antimicrobial properties.
1) Zhou T, Wang N, Xue Y, Ding T, Liu X, Mo X, Sun J. 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, Bartolo PJ. Advanced biofabrication strategies for skin regeneration and repair. Nanomedicine, 8(4): 603-621 (2013).