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. Harding K, Kirsner R, Lee D, Mulder G, Serena T.
International consensus: Acellular matrices for the
treatment of wounds. An expert working group review.
Wounds International, London 2010.
21. Olafsdottir A, Thorlacius GE, Omarsdottir S, Olafsdottir
ES, Vikingsson A, Freysdottir J, et al. A heteroglycan
from the cyanobacterium Nostoc commune modulates
LPS-induced inflammatory cytokine secretion by THP-1
monocytes through phosphorylation of ERK1/2 and Akt.
Phytomedicine Int J Phytother Phytopharm 2014; 21: 1451-
7.
22. Storgard C, Mikolon D, Stupack DG. Angiogenesis assays
in the chick CAM. Methods Mol Biol Clifton NJ 2005; 294:
123-36.
23. Kafienah W, Buttle DJ, Burnett D, Hollander AP. Cleavage
of native type I collagen by human neutrophil elastase.
Biochem J 1998; 330 ( Pt 2): 897-902.
24. Monici M. Cell and tissue autofluorescence research and
diagnostic applications. Biotechnol Annu Rev 2005; 11:
227-56.
25. Epstein EHJ. (Alpha1(3))3 human skin collagen. 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. Medical devices containing materials derived from animal
sources (except for in vitro diagnostic devices), guidance
for FDA reviewers and industry; availability--FDA.
Notice. Fed Regist 1998; 63: 60009-10.
32. Crapo PM, Gilbert TW, Badylak SF. An overview of tissue
and whole organ decellularization processes. Biomaterials
2011; 32: 3233-43.
33. Bechtel PJ. Properties of Different Fish Processing
By-Products from Pollock, Cod and Salmon. J Food
Process Preserv 2003; 27: 101-16.
34. McDaniel JC, Massey K, Nicolaou A. Fish oil supple-
mentation alters levels of lipid mediators of inflammation
in microenvironment of acute human wounds. Wound
Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair
Soc 2011; 19: 189-200.