Wound healing grafts: Omega-3 fatty acid lipid content differentiates the lipid profiles of acellular Atlantic cod skin from traditional dermal substitutes
Aristotelis Kotronoulas
Center for Systems Biology, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorHulda S. Jónasdóttir
Center for Systems Biology, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorRósa S. Sigurðardóttir
Center for Systems Biology, University of Iceland, Reykjavik, Iceland
Department of Biochemistry and Molecular Biology, Medical School, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorSkarphéðinn Halldórsson
Center for Systems Biology, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorGuðmundur G. Haraldsson
The Science Institute, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorCorresponding Author
Óttar Rolfsson
Center for Systems Biology, University of Iceland, Reykjavik, Iceland
Department of Biochemistry and Molecular Biology, Medical School, University of Iceland, Reykjavik, Iceland
Correspondence
Óttar Rolfsson, Center for Systems Biology, University of Iceland, Sturlugata 8, Reykjavik 101, Iceland.
Email: [email protected]
Search for more papers by this authorAristotelis Kotronoulas
Center for Systems Biology, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorHulda S. Jónasdóttir
Center for Systems Biology, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorRósa S. Sigurðardóttir
Center for Systems Biology, University of Iceland, Reykjavik, Iceland
Department of Biochemistry and Molecular Biology, Medical School, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorSkarphéðinn Halldórsson
Center for Systems Biology, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorGuðmundur G. Haraldsson
The Science Institute, University of Iceland, Reykjavik, Iceland
Search for more papers by this authorCorresponding Author
Óttar Rolfsson
Center for Systems Biology, University of Iceland, Reykjavik, Iceland
Department of Biochemistry and Molecular Biology, Medical School, University of Iceland, Reykjavik, Iceland
Correspondence
Óttar Rolfsson, Center for Systems Biology, University of Iceland, Sturlugata 8, Reykjavik 101, Iceland.
Email: [email protected]
Search for more papers by this authorAbstract
Acellular fish skin (ACS) has emerged as a dermal substitute used to promote wound healing with decreased scar formation and pain relief that may be due to polyunsaturated fatty acid (PUFA) content. However, the PUFA content of ACS is still unknown. The aim of this study was to compare the total fatty acids and lipid profiles of ACS to two bovine-based grafts and standard of care human cadaver skin (HCS). Furthermore, there was also the goal to assess the capability of ACS lipid content to enhance wound healing. The fatty acid analysis was performed with GC–FID, and an LC–MS untargeted method was developed in order to the analyse the lipid profiles of the grafts was. The enhancement of wound healing by the ACS extract was investigated in vitro on HaCat cells. Our results showed that ACS had the highest content of PUFA (27.0 ± 1.43% of their total fatty acids), followed by HCS (20.6 ± 3.9%). The two grafts of bovine origin presented insignificant PUFA amounts. The majority of the PUFAs found in ACS were omega-3, and in HCS, they were omega-6. The untargeted lipidomics analysis demonstrated that ACS grafts were characterized by phosphatidylcholine containing either 20:5 or 22:6 omega-3 PUFA. The ACS lipid extract increased the HaCat cells migration and enhanced wound closure 4 hr earlier versus control. Our study demonstrated that ACS has a lipid profile that is distinct from other wound healing grafts, that PUFAs are maintained in ACS post-processing as phosphatidylcholine, and that ACS lipid content influences wound healing properties.
CONFLICT OF INTEREST
The authors have declared that there is no conflict of interest.
Supporting Information
| Filename | Description |
|---|---|
| term3005-sup-0001-Supporting Information.docxWord 2007 document , 2.5 MB |
Table S1: Area and weight of the each extracted graft and the corresponding lipid yield Figure S1: Comparison of the fatty acid content of the analyzed grafts, as calculated by the to indipendent laboratories in Iceland and in Norway Figure S2: Cluster analysis of detected m/z features for the analyzed grafts Figure S3: Mass spectra obtained after the fragmentation (CE: 40 to 70 V) of selected masses that correspond to the phoshatidylcholines of interest Figure S3-1: Fragmentation pattern in ESI (+) of the selected mass m/z 764.56 Figure S3-2: Fragmentation pattern in ESI (+) of the selected mass m/z 808.59 Figure S3-3: Fragmentation pattern in ESI (+) of the selected mass m/z 778.54 Figure S3-4: Fragmentation pattern in ESI (+) of the selected mass m/z 832.58 Figure S3-5: Fragmentation pattern in ESI (+) of the selected mass m/z 834.61 Figure S3-6: Fragmentation pattern in ESI (+) of the selected mass m/z 824.56 Figure S3-7: Fragmentation pattern in ESI (+) of the selected mass m/z 850.57 Figure S4: Proliferation assay of HaCat cells treated with either medium containing 12 mg/mL lipid extract solution dissolved in ethanol (treated, n = 6), or medium containing ethanol (vehicle, n = 6) or only medium (control, n = 6) |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- Alexander, J. W., & Supp, D. M. (2014). Role of arginine and omega-3 fatty acids in wound healing and infection. Adv Wound Care (New Rochelle), 3(11), 682–690. https://doi.org/10.1089/wound.2013.0469
- Bagga, D., Wang, L., Farias-Eisner, R., Glaspy, J. A., & Reddy, S. T. (2003). Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proceedings of the National Academy of Sciences of the United States of America, 100(4), 1751–1756. https://doi.org/10.1073/pnas.0334211100
- Baldursson, B. T., Kjartansson, H., Konradsdottir, F., Gudnason, P., Sigurjonsson, G. F., & Lund, S. H. (2015). Healing rate and autoimmune safety of full-thickness wounds treated with fish skin acellular dermal matrix versus porcine small-intestine submucosa: A noninferiority study. The International Journal of Lower Extremity Wounds, 14(1), 37–43. https://doi.org/10.1177/1534734615573661
- Bird, S. S., Marur, V. R., Sniatynski, M. J., Greenberg, H. K., & Kristal, B. S. (2011). Serum lipidomics profiling using LC-MS and high-energy collisional dissociation fragmentation: Focus on triglyceride detection and characterization. Analytical Chemistry, 83(17), 6648–6657. https://doi.org/10.1021/ac201195d
- Bligh, E. G., & Dyer, W. J. (1959). A rapid method of total lipid extraction and purification. Canadian Journal of Biochemistry and Physiology, 37(8), 911–917. https://doi.org/10.1139/o59-099
- Boireau-Adamezyk, E., Baillet-Guffroy, A., & Stamatas, G. N. (2014). Age-dependent changes in stratum corneum barrier function. Skin Research and Technology, 20(4), 409–415. https://doi.org/10.1111/srt.12132
- Calder, P. C. (2006). n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. The American Journal of Clinical Nutrition, 83(6 Suppl), 1505S–1519S. https://doi.org/10.1093/ajcn/83.6.1505S
- Calder, P. C. (2017). Omega-3 fatty acids and inflammatory processes: From molecules to man. Biochemical Society Transactions, 45(5), 1105–1115. https://doi.org/10.1042/BST20160474
- Chiurchiu, V., Leuti, A., Dalli, J., Jacobsson, A., Battistini, L., Maccarrone, M., & Serhan, C. N. (2016). Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses. Science Translational Medicine, 8(353), 353ra111), 353ra111. https://doi.org/10.1126/scitranslmed.aaf7483
- Cholewski, M., Tomczykowa, M., & Tomczyk, M. (2018). A comprehensive review of chemistry, sources and bioavailability of omega-3 fatty acids. Nutrients, 10(11). https://doi.org/10.3390/nu10111662
- Dennis, E. A., & Norris, P. C. (2015). Eicosanoid storm in infection and inflammation. Nature Reviews. Immunology, 15(8), 511–523. https://doi.org/10.1038/nri3859
- Dorweiler, B., Trinh, T. T., Dunschede, F., Vahl, C. F., Debus, E. S., Storck, M., & Diener, H. (2018). The marine Omega3 wound matrix for treatment of complicated wounds: A multicenter experience report. Gefässchirurgie, 23(Suppl 2), 46–55. https://doi.org/10.1007/s00772-018-0428-2
- Eiriksson, F. F., Rolfsson, O., Ogmundsdottir, H. M., Haraldsson, G. G., Thorsteinsdottir, M., & Halldorsson, S. (2018). Altered plasmalogen content and fatty acid saturation following epithelial to mesenchymal transition in breast epithelial cell lines. The International Journal of Biochemistry & Cell Biology, 103, 99–104. https://doi.org/10.1016/j.biocel.2018.08.003
- Gore, M. A., & De, A. S. (2010). Deceased donor skin allograft banking: Response and utilization. Indian journal of plastic surgery: official publication of the Association of Plastic Surgeons of India, 43(Suppl), S114–S120. https://doi.org/10.4103/0970-0358.70732
- Gorjao, R., Azevedo-Martins, A. K., Rodrigues, H. G., Abdulkader, F., Arcisio-Miranda, M., Procopio, J., & Curi, R. (2009). Comparative effects of DHA and EPA on cell function. Pharmacology & Therapeutics, 122(1), 56–64. https://doi.org/10.1016/j.pharmthera.2009.01.004
- Hellmann, J., Sansbury, B. E., Wong, B., Li, X., Singh, M., Nuutila, K., … Spite, M. (2018). Biosynthesis of D-series resolvins in skin provides insights into their role in tissue repair. The Journal of Investigative Dermatology, 138(9), 2051–2060. https://doi.org/10.1016/j.jid.2018.03.1498
- Hellmann, J., Tang, Y., & Spite, M. (2012). Proresolving lipid mediators and diabetic wound healing. Current Opinion in Endocrinology, Diabetes, and Obesity, 19(2), 104–108. https://doi.org/10.1097/MED.0b013e3283514e00
- Irons, R. F., Cahill, K. W., Rattigan, D. A., Marcotte, J. H., Fromer, M. W., Chang, S., … Caputo, F. J. (2018). Acceleration of diabetic wound healing with adipose-derived stem cells, endothelial-differentiated stem cells, and topical conditioned medium therapy in a swine model. Journal of Vascular Surgery, 68(6S), 115S–125S. https://doi.org/10.1016/j.jvs.2018.01.065
- Kendall, A. C., Pilkington, S. M., Massey, K. A., Sassano, G., Rhodes, L. E., & Nicolaou, A. (2015). Distribution of bioactive lipid mediators in human skin. The Journal of Investigative Dermatology, 135(6), 1510–1520. https://doi.org/10.1038/jid.2015.41
- Kohli, P., & Levy, B. D. (2009). Resolvins and protectins: Mediating solutions to inflammation. British Journal of Pharmacology, 158(4), 960–971. https://doi.org/10.1111/j.1476-5381.2009.00290.x
- Krishnan, S., Sekar, S., Katheem, M. F., Krishnakumar, S., & Sastry, T. P. (2012). Fish scale collagen—A novel material for corneal tissue engineering. Artificial Organs, 36(9), 829–835. https://doi.org/10.1111/j.1525-1594.2012.01452.x
- Lee, Y., Choo, J., Kim, S. J., Heo, G., Pothoulakis, C., Kim, Y. H., & Im, E. (2017). Analysis of endogenous lipids during intestinal wound healing. PLoS ONE, 12(8), e0183028. https://doi.org/10.1371/journal.pone.0183028
- Magnusson, S., Baldursson, B. T., Kjartansson, H., Rolfsson, O., & Sigurjonsson, G. F. (2017). Regenerative and antibacterial properties of acellular fish skin grafts and human amnion/chorion membrane: Implications for tissue preservation in combat casualty care. Military Medicine, 182(S1), 383–388. https://doi.org/10.7205/MILMED-D-16-00142
- Magnusson, S., Baldursson, B. T., Kjartansson, H., Thorlacius, G. E., Axelsson, I., Rolfsson, O., … Sigurjonsson, G. F. (2015). Decellularized fish skin: Characteristics that support tissue repair. Læknablađiđ, 101(12), 567–573. https://doi.org/10.17992/lbl.2015.12.54
- Menon, R., Krzyszczyk, P., & Berthiaume, F. (2017). Pro-resolution potency of resolvins D1, D2 and E1 on neutrophil migration and in dermal wound healing. Nano Life, 7(1). https://doi.org/10.1142/S1793984417500027
- NHS UK, organ donation web page, Retrieved October 14 2019, from: https://www.organdonation.nhs.uk/helping-you-to-decide/about-organ-donation/what-can-you-donate/tissue/In
- Osman, F., Jaswir, I., Khaza'ai, H., & Hashim, R. (2007). Fatty acid profiles of fin fish in Langkawi Island, Malaysia. Journal of Oleo Science, 56(3), 107–113. https://doi.org/10.5650/jos.56.107
- Paglia, G., & Astarita, G. (2017). Metabolomics and lipidomics using traveling-wave ion mobility mass spectrometry. Nature Protocols, 12(4), 797–813. https://doi.org/10.1038/nprot.2017.013
- Porter, N. A., Caldwell, S. E., & Mills, K. A. (1995). Mechanisms of free radical oxidation of unsaturated lipids. Lipids, 30(4), 277–290. https://doi.org/10.1007/bf02536034
- Rogers, J., Harding, C., Mayo, A., Banks, J., & Rawlings, A. (1996). Stratum corneum lipids: The effect of ageing and the seasons. Archives of Dermatological Research, 288(12), 765–770. https://doi.org/10.1007/bf02505294
- Serhan, C. N. (2014). Pro-resolving lipid mediators are leads for resolution physiology. Nature, 510(7503), 92–101. https://doi.org/10.1038/nature13479
- Serhan, C. N., & Levy, B. D. (2018). Resolvins in inflammation: Emergence of the pro-resolving superfamily of mediators. The Journal of Clinical Investigation, 128(7), 2657–2669. https://doi.org/10.1172/JCI97943
- Serhan, C. N., & Petasis, N. A. (2011). Resolvins and protectins in inflammation resolution. Chemical Reviews, 111(10), 5922–5943. https://doi.org/10.1021/cr100396c
- Silva, J. R., Burger, B., Kuhl, C. M. C., Candreva, T., Dos Anjos, M. B. P., & Rodrigues, H. G. (2018). Wound healing and omega-6 fatty acids: From inflammation to repair. Mediators of Inflammation, 2018, 2503950, 1–17. https://doi.org/10.1155/2018/2503950
- Sjovall, P., Skedung, L., Gregoire, S., Biganska, O., Clement, F., & Luengo, G. S. (2018). Imaging the distribution of skin lipids and topically applied compounds in human skin using mass spectrometry. Scientific Reports, 8(1), 16683. https://doi.org/10.1038/s41598-018-34286-x
- Spite, M., Claria, J., & Serhan, C. N. (2014). Resolvins, specialized proresolving lipid mediators, and their potential roles in metabolic diseases. Cell Metabolism, 19(1), 21–36. https://doi.org/10.1016/j.cmet.2013.10.006
- Spite, M., Norling, L. V., Summers, L., Yang, R., Cooper, D., Petasis, N. A., … Serhan, C. N. (2009). Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature, 461(7268), 1287–1291. https://doi.org/10.1038/nature08541
- Starr, N. J., Johnson, D. J., Wibawa, J., Marlow, I., Bell, M., Barrett, D. A., & Scurr, D. J. (2016). Age-related changes to human stratum corneum lipids detected using time-of-flight secondary ion mass spectrometry following in vivo sampling. Analytical Chemistry, 88(8), 4400–4408. https://doi.org/10.1021/acs.analchem.5b04872
- Tang, Y., Zhang, M. J., Hellmann, J., Kosuri, M., Bhatnagar, A., & Spite, M. (2013). Proresolution therapy for the treatment of delayed healing of diabetic wounds. Diabetes, 62(2), 618–627. https://doi.org/10.2337/db12-0684
- Tognetti, L., Pianigiani, E., Ierardi, F., Mariotti, G., Perotti, R., Di Lonardo, A., … Fimiani, M. (2017). Current insights into skin banking: Storage, preservation and clinical importance of skin allografts. Journal of Biorepository Science for Applied Medicine, 5, 41–56. https://doi.org/10.2147/BSAM.S115187
10.2147/BSAM.S115187 Google Scholar
- Wymann, M. P., & Schneiter, R. (2008). Lipid signalling in disease. Nature Reviews. Molecular Cell Biology, 9(2), 162–176. https://doi.org/10.1038/nrm2335
- Yamamoto, T., Iwase, H., King, T. W., Hara, H., & Cooper, D. K. C. (2018). Skin xenotransplantation: Historical review and clinical potential. Burns, 44(7), 1738–1749. https://doi.org/10.1016/j.burns.2018.02.029
- Yang, C. K., Polanco, T. O., & Lantis, J. C. 2nd. (2016). A prospective, postmarket, compassionate clinical evaluation of a novel acellular fish-skin graft which contains omega-3 fatty acids for the closure of hard-to-heal lower extremity chronic ulcers. Wounds, 28(4), 112–118.
