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Læknablaðið - 01.12.2015, Blaðsíða 17

Læknablaðið - 01.12.2015, Blaðsíða 17
LÆKNAblaðið 2015/101 573 R A N N S Ó K N ENgLISH SUMMArY introduction: Acellular fish skin of the Atlantic cod (Gadus morhua) is being used to treat chronic wounds. The prevalence of diabetes and the comorbidity of chronic wounds is increasing globally. The aim of the study was to assess the biocompatibility and biological characteristics of acellular fish skin, important for tissue repair. Materials and methods: The structure of the acellular fish skin was examined with microscopy. Biocompatibility of the graft was conducted by a specialized certified laboratory. Protein extracts from the material were analyzed using gel electrophoresis. Cytokine levels were measured with an enzyme linked immunosorbent assay (ELISA). Angiogenic properties were assessed with a chick chorioallantoic membrane (chick CAM) assay. Results: The structure of acellular fish skin is porous and the material is biocompatible. Electrophoresis revealed proteins around the size 115- 130 kDa, indicative of collagens. The material did not have significant effect on IL-10, IL-12p40, IL-6 or TNF-α secretion from monocytes or macrophages. Acellular fish skin has significant effect on angiogenesis in the chick CAM assay. Conclusion: The acellular fish skin is not toxic and is not likely to pro- mote inflammatory responses. The graft contains collagen I, promotes angiogenesis and supports cellular ingrowth. Compared to similar products made from mammalian sources, acellular fish skin does not confer a disease risk and contains more bioactive compounds, due to less severe processing. Decellularized fish skin: characteristics that support tissue repair Skuli Magnusson1, Baldur Tumi Baldursson1,2, Hilmar Kjartansson1,2, Gudny Ella Thorlacius3, Ivar Axelsson1, ottar Rolfsson4, Petur Henry Petersen3, Gudmundur Fertram Sigurjonsson1 1Kerecis Limited, Eyraragata 2, 400 Isafjordur, Iceland, 2Landspitali - The National University Hospital of Iceland, 3Faculty of Medicine, University of Iceland, 4Center for Systems Biology, University of Iceland. key words: Fish skin, extracellular matrix, acellular dermal graft, wound healing, tissue repair. Correspondence: Baldur Tumi Baldursson, btb@kerecis.com Heimildir 1. accessdata.fda.gov/cdrh_docs/pdf13/K132343.pdf - febrú- ar 2015. 2. Baldursson BT, Kjartansson H, Konradsdottir F, Gudnason P, Sigurjonsson GF, Lund SH. Healing rate and autoimm- une safety of full-thickness wounds treated with fish skin acellular dermal matrix versus porcine small-intestine submucosa: a noninferiority study. Int J Low Extrem Wounds 2015; 14: 37-41. 3. Chang J, DeLillo NJ, Khan M, Nacinovich MR. Review of small intestine submucosa extracellular matrix technology in multiple difficult-to-treat wound types. Wounds Compend Clin Res Pract 2013; 25: 113-20. 4. Hodde J, Hiles M. Virus safety of a porcine-derived medical device: evaluation of a viral inactivation method. Biotechnol Bioeng 2002; 79: 211-6. 5. Calder PC. Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance. Biochim Biophys Acta 2015; 1851: 469-84. 6. Mil-Homens D, Bernardes N, Fialho AM. The antibacterial properties of docosahexaenoic omega-3 fatty acid against the cystic fibrosis multiresistant pathogen Burkholderia cenocepacia. FEMS Microbiol Lett 2012; 328: 61-9. 7. Imai Y. Role of omega-3 PUFA-derived mediators, the protectins, in influenza virus infection. Biochim Biophys Acta 2015; 1851: 496-502. 8. O’Meara S, Cullum N, Majid M, Sheldon T. Systematic reviews of wound care management: (3) antimicrobial agents for chronic wounds; (4) diabetic foot ulceration. Health Technol Assess Winch Engl 2000; 4: 1-237. 9. Lam DW, LeRoith D. The worldwide diabetes epidemic. Curr Opin Endocrinol Diabetes Obes 2012; 19: 93-6. 10. Reiber GE, Lipsky BA, Gibbons GW. The burden of diabetic foot ulcers. Am J Surg 1998; 176: 5S-10S. 11. Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc 2009; 17: 763-71. 12. Iorio ML, Shuck J, Attinger CE. Wound healing in the upper and lower extremities: a systematic review on the use of acellular dermal matrices. Plast Reconstr Surg 2012; 130: 232S-41S. 13. Badylak SF. Decellularized allogeneic and xenogeneic tissue as a bioscaffold for regenerative medicine: factors that influence the host response. Ann Biomed Eng 2014; 42: 1517-27. 14. Kjartansson H, Olafsson IH, Karason S, Thorisson H, Baldursson BT, Gunnarsson E, et al. Use of Acellular Fish Skin for Dura Repair in an Ovine Model: A Pilot Study. Open J Mod Neurosurg 2015; 5: 124-36. 15. Rakers S, Gebert M, Uppalapati S, Meyer W, Maderson P, Sell AF, et al. “Fish matters”: the relevance of fish skin biology to investigative dermatology. Exp Dermatol 2010; 19: 313-24. 16. Hawkes JW. The structure of fish skin. I. General organiza- tion. Cell Tissue Res 1974; 149: 147-58. 17. Rakers S, Niklasson L, Steinhagen D, Kruse C, Schauber J, Sundell K, et al. Antimicrobial peptides (AMPs) from fish epidermis: perspectives for investigative dermatology. J Invest Dermatol 2013; 133: 1140-9. 18. Rayment EA, Upton Z. Finding the culprit: a review of the influences of proteases on the chronic wound environ- ment. Int J Low Extrem Wounds 2009; 8: 19-27. 19. Gibson D, Cullen B, Legerstee R, Harding K, Schultz G. MMps Made Easy. Wounds Int 2009; 1: 1-6. 20. 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Release by pepsin digestion and preponderance in fetal life. J Biol Chem 1974; 49: 3225-31. 26. Cheah KS, Stoker NG, Griffin JR, Grosveld FG, Solomon E. Identification and characterization of the human type II collagen gene (COL2A1). Proc Natl Acad Sci U S A 1985; 82: 2555-9. 27. 26th Annual Meeting of the Wound Healing Society: SAWC-Spring/WHS Joint Meeting Sept 26–28, 2015. Wound Repair Regen 2015; 23: A49-53. 28. Pradhan L, Cai X, Wu S, Andersen ND, Martin M, Malek J, et al. Gene expression of pro-inflammatory cytokines and neuropeptides in diabetic wound healing. J Surg Res 2011; 167: 336-42. 29. Turner NJ, Badylak SF. Biologic scaffolds for musculo- tendinous tissue repair. Eur Cell Mater 2013; 25: 130-43. 30. Li J, Zhang Y-P, Kirsner RS. Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix. Microsc Res Tech 2003; 60: 107-14. 31. 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