Derleme
BibTex RIS Kaynak Göster

DESELÜLERİZASYON YÖNTEMLERİ VE DOKULARDA KULLANIMI

Yıl 2017, Cilt: 2 Sayı: 2, 19 - 34, 29.12.2017

Öz

Deselülerize
edilmiş doku ve organlar çeşitli doku mühendisliği ve rejeneratif tıp
uygulamalarında başarıyla kullanılmaktadır. Ekstraselüler matristen elde edilen
biyolojik bir iskele, işlem görecek dokudan hücreleri etkin bir şekilde ortadan
kaldıran çeşitli deselülerizasyon yöntemleri ile üretilebilir. Kullanılan deselülerizasyon
yöntemleri dokuların ve organların yapısına göre değişir. Hücrelerin bir
dokudan çıkarılması, dokunun kaynağına ve kullanılan spesifik fiziksel,
kimyasal ve enzimatik yöntemlere bağlıdır. Bu yöntemlerin her biri geri kalan
hücre dışı matrisin (ECM) yapısındaki biyokimyasal bileşimini, dokunun ince
yapısını  (ultrastrüktürünü) ve mekanik
davranışını etkiler. Bu makalede en sık kullanılan deselülerizasyon yöntemleri tanıtılarak
ve bu yöntemlerin biyolojik doku iskelesi materyali üzerindeki etkileri ele
alınmaktadır.

Kaynakça

  • Affonso da Costa, F.D., Dohmen, P.M., Lopes, S.V., Lacerda, G., Pohl, F., Vilani, R., Affonso Da Costa, M.B., Vieira, E.D., Yoschi, S., Konertz, W., Affonso da Costa, I., 2004. Comparison of Cryopreserved Homografts and Decellularized Porcine Heterografts Implanted in sheep. Artif Organs, 28, 366–370.
  • Akbay, E., Onur, M.A., 2016. Rejeneratif Tıpta Kullanılan Organ ve Doku Deselülerizasyon Yöntemleri. Türk Yaşam Bilimleri Dergisi, 1(2), 96-102.
  • Alhamdani, M.S.S., Schroder, C., Werner, J., Giese, N., Bauer, A., Hoheisel, J.D., 2010. Single-Step Procedure for the Isolation of Proteins at Near-Native Conditions from Mammalian Tissue for Proteomic Analysis on Antibody Microarrays. Journal of Proteome Research, 9, 963–971.
  • Bader, A., Schilling, T., Teebken, O.E., Brandes, G., Herden, T., Steinhoff, G., Haverich, A., 1998. Tissue Engineering of Heart Valves—Human Endothelial Cell Seeding of Detergent Acellularized Porcine Valves. European Journal of Cardio-Thoracic Surgery, 14, 279–284.
  • Badylak, S.F., Tullius, R., Kokini, K., Shelbourne, K.D., Klootwyk, T., Voytik, S.L., Kraine, M.R., Simmons, C., 1995. The Use of Xenogeneic Small İntestinal Submucosa as a Biomaterial for Achilles Tendon Repair in a Dog Model. Journal of Biomedical Materials Research, 29, 977–985.
  • Bayram, C., 2012. Hücre ve Doku Mühendisliği Araştırma Grubu. Nanoteknoloji ve Nanotıp Bilim Dergisi (N@nobülten), 18-27.
  • Brown, B.N., Freund, J.M., Han, L., Rubin, J.P., Reing, J.E., Jeffries, E.M., Wolf, M.T., Tottey, S., Barnes, C.A., Ratner, B.D., Badylak, S.F., 2011. Comparison of Three Methods for the Derivation of a Biologic Scaffold Composed of Adipose Tissue Extracellular Matrix. Tissue Engineering Part C Methods, 17(4), 411-421.
  • Brown, B., Lindberg, K., Reing, J., Stolz, D.B., Badylak, S.F., 2006. The Basement Membrane Component of Biologic Scaffolds Derived From Extracellular Matrix. Tissue Engineering, 12, 519-526.
  • Cartmell, J.S., Dunn, M.G., 2000. Effect of Chemical Treatments on Tendon Cellularity and Mechanical Properties. Journal of Biomedical Materials Research, 49, 134–140.
  • Chen, F., Yoo, J.J., Atala, A., 1999. Acellular Collagen Matrix as a Possible ‘‘off the shelf’’ Biomaterial for Urethral Repair. Urology, 54, 407–410.
  • Chen, R.N., Ho, H.O., Tsai, Y.T., Sheu, M.T., 2004. Process Development of an Acellular Dermal Matrix (ADM) for Biomedical Applications. Biomaterials, 25, 2679–2686.
  • Chen, V.J., Ma, P.X., 2004. Nano-Fibrous Poly(L-Lactic Acid) Scaffolds With İnterconnected Spherical Macropores. Biomaterials, 25, 2065-2073.
  • Cole, M.B.J., 1984. Alteration of Cartilage Matrix Morphology with Histological Processing. Journal of Microscopy, 133, 129–40.
  • Cortiella, J., Niles, J., Cantu, A., Brettler, A., Pham, A., Vargas, G., Winston, S., Wang, J., Walls, S., Nichols, J.E., 2010. Influence of Acellular Natural Lung Matrix on Murine Embryonic Stem Cell Differentiation and Tissue Formation. Tissue Engineering Part A, 16(8), 2565-2580.
  • Courtman, D.W., Pereira, C.A., Kashef, V., McComb, D., Lee, J.M., Wilson, G.J., 1994. Development of a Pericardial Acellular Matrix Biomaterial: Biochemical and Mechanical Effects of Cell Extraction. Journal of Biomedical Materials Research, 28, 655–666.
  • Crapo, P.M., Gilbert, T.W., Badylak, S.F., Badylak, D.V.M., 2011. An Overview of Tissue and Whole Organ Decellularization Processes. Biomaterials, 32, 3233–3243.
  • Çeviker, K., Özseven, Ö.S., Şeker, G.C., Rahim, M., Kılıçarslan, Ş., Yazkan, R., 2017. Biyolojik Damarsal Greft Üretiminde Hücresizleştirme Metodları; Güncel Literatür Derlemesi. SDÜ Tıp Fakültesi Dergisi, 24(1), 12-23.
  • Dahl, S.L., Koh, J., Prabhakar, V., Niklason, L.E., 2003. Decellularized native and engineered arterial scaffolds for transplantation. Cell Transplant, 12, 659–666.
  • De Filippo, R.E., Yoo, J.J., Atala, A., 2002. Urethral Replacement Using Cell Seeded Tubularized Collagen Matrices. The Journal of Urology, 168, 1789–1792
  • Elder, B.D., Kim, D.H., Athanasiou, K.A., 2010. Developing an Articular Cartilage Decellularization Process Toward Facet Joint Cartilage Replacement. Neurosurgery, 66, 722–727.
  • Falke, G., Yoo, J.J., Kwon, T.G., Moreland. R., Atala. A., 2003. Formation of Corporal Tissue Architecture In Vivo Using Human Cavernosal Muscle and Endothelial Cells Seeded on Collagen Matrices. Tissue Engineering, 9, 871–879.
  • Faulk, D.M., Carruthers, C.A., Warner, H.J., Kramer, C.R., Reing, J.E., Zhang, L., D'Amore, A., Badylak, S.F., 2014. The Effect of Detergents on the Basement Membrane Complex of a Biologic Scaffold Biomaterial. Acta Biomaterial, 10, 1-21.
  • Fermor, H.L., Russell, S.L., Williams, S., Fisher, J., Ingham, E., 2015. Development and Characterisation of a Desellularised Bovine Osteochondral Biomaterial for Cartilage Repair. Journal of Materials Science: Materials in Medicine, 26, 186.
  • Flynn, L.E., 2010. The Use of Decellularized Adipose Tissue to Provide an Inductive Microenvironment for the Adipogenic Differentiation of Human Adiposederived Stem Cells. Biomaterials, 31, 4715–4724.
  • Freytes, D.O., Badylak, S.F., Webster, T.J., Geddes, L.A., Rundell, A.E., 2004. Biaxial strength of multilaminated extracellular matrix scaffolds. Biomaterials, 25, 2353–2361.
  • Fu, R.H., Wang, Y.C., Liu, S.P., Shih, T.R., Lin, H.L., Chen, Y.M., Sung, J.H., Lu, C.H., Wei, J.R., Wang, Z.W., Huang, S.J., Tsai, C.H., Shyu, W.C., Lin, S.Z., 2014. Decellularization and Recellularization Technologies in tissue Engineering. Cell Transplantation, 23, 621–630.
  • Funamoto, S., Nam, K., Kimura, T., Murakoshi, A., Hashimoto, Y., Niwaya, K., Kitamura, S., Fujisato, T., Kishida, A., 2010. The Use of High-Hydrostatic Pressure Treatment to Decellularize Blood Vessels. Biomaterials, 31(13), 3590-3595.
  • Gailit, J., Ruoslahti, E., 1988. Regulation of the Fibronectin Receptor Affinity by Divalent Cations. The Journal of Biological Chemistry, 263, 12927–12932.
  • Gamba, P.G., Conconi, M.T., Lo Piccolo, R., Zara, G., Spinazzi, R., Parnigotto, P.P., 2002. Experimental Abdominal Wall Defect Repaired with Acellular Matrix. Pediatric Surgery International, 18, 327–331.
  • Gilbert, T.W., Sellaro, T.L., Badylak, S.F., 2006. Decellularization of Tissue and Organs. Elsevier Biomaterials, 27, 3675-3683.
  • Gilbert, T.W., Wognum, S., Joyce, E.M., Freytes, D.O., Sacks, M.S., Badylak, S.F., 2008. Collagen Fiber Alignment and Biaxial Mechanical Behavior of Porcine Urinary Bladder Derived Extracellular Matrix. Biomaterials, 29, 4775–4782.
  • Goissis, G., Suzigan, S., Parreira, D.R., Maniglia, J.V., Braile, D.M., Raymundo, S., 2000. Preparation and Characterization of Collagen–Elastin Matrices From Blood Vessels Intended as Small Diameter Vascular Grafts. Artif Organs, 24, 217–223.
  • Gorschewsky, O., Klakow, A., Riechert, K., Pitzl, M., Becker, R., 2005. Clinical Comparison of the Tutoplast Allograft And Autologous Patellar Tendon (Bonepatellar Tendon-Bone) for the Reconstruction of the Anterior Cruciate Ligament: 2- and 6-Year Results. The American Journal of Sports Medicine, 33, 1202–1209.
  • Grauss, R.W., Hazekamp, M.G., Oppenhuizen, F., van Munsteren, C.J., Gittenberger-de, Groot, A.C., DeRuiter, M.C., 2005. Histological Evaluation of Decellularised Porcine Aortic Valves: Matrix Changes Due to Different Decellularisation Methods. European Journal of Cardiothoracic Surgery, 27, 566–571.
  • Grauss, R.W., Hazekamp, M.G., van Vliet, S., Gittenberger-de Groot, A.C., DeRuiter, M.C., 2003. Decellularization of Rat Aortic Valve Allografts Reduces Leaflet Destruction and Extracellular Matrix Remodeling. The Journal of Thoracic and Cardiovascular Surgery , 126, 2003–2010.
  • Gui, L., Chan, S., Breuer, C.K., Niklason, L.E., 2010. Novel Utilization of Serum in Tissue Decellularization. Tissue Engineering Part C, Methods, 16, 173–184.
  • Gulati, A.K., 1988. Evaluation of Acellular and Cellular Nerve Grafts in Repair of Rat Peripheral Nerve. Journal of Neurosurgery, 68, 117–123.
  • Hilbert, S.L., Yanagida, R., Souza, J., Wolfinbarger, L., Jones, A.L., Krueger, P., Stearns, G., Bert, A., Hopkins, R.A., 2004. Prototype Anionic Detergent Technique Used to Decellularize Allograft Valve Conduits Evaluated in the Right Ventricular Outflow Tract in Sheep. The Journal of Heart Valve Disease, 13, 831–840.
  • Hodde, J.P., Badylak, S.F., Brightman, A.O., Voytik-Harbin, S.L., 1996. Glycosaminoglycan Content of Small Intestinal Submucosa: A Bioscaf- Fold For Tissue Replacement. Tissue Engineering, 2, 209–217.
  • Hodde, J., Hiles, M., 2002. Virus Safety of a Porcine-Derived Medical Device: Evaluation of a Viral Inactivation Method. Biotechnology and Bioengineering, 79, 211–216.
  • Hodde, J., Record, R., Tullius, R., Badylak, S., 2002a. Fibronectin Peptides Mediate HMEC Adhesion to Porcine-Derived Extracellular Matrix. Biomaterials, 23, 1841–1848.
  • Hodde, J.P., Record, R.D., Tullius, R.S., Badylak, S.F., 2002b. Retention of Endothelial Cell Adherence to Porcine-Derived Extracellular Matrix After Disinfection and Sterilization. Tissue Engineering, 8, 225–234.
  • Hopkinson, A., Shanmuganathan, V.A., Gray, T., Yeung, A.M., Lowe, J., James, D.K., Dua, H.S., 2008. Optimization of Amniotic Membrane (AM) Denuding for Tissue Engineering. Tissue Engineering Part C Methods, 14(4), 371-381.
  • Hudson, T.W., Liu, S.Y., Schmidt, C.E., 2004. Engineering an Improved Acellular Nerve Graft Via Optimized Chemical Processing. Tissue Engineering, 10, 1346–1358.
  • Hudson, T.W., Zawko, S., Deister, C., Lundy, S., Hu, C.Y., Lee, K., Schmidt, C.E., 2004. Optimized Acellular Nerve Graft is Immunologically Tolerated and Supports Regeneration. Tissue Engineering, 10(11-12), 1641-1651.
  • Hrebikova, H., Diaz, D., Mokry, J., 2015. Chemical Decellularization: A Promising Approach For Preparation Of Extracellular Matrix. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 159(1):12-17
  • Jackson, D.W., Grood, E.S., Arnoczky, S.P., Butler, D.L., Simon, T.M., 1987. Cruciate Reconstruction Using Freeze Dried Anterior Cruciate Ligament Allograft and A Ligament Augmentation Device (LAD). An Experimental Study in a Goat Model. The American Journal of Sports Medicine, 15, 528–538.
  • Jackson, D.W., Windler, G.E., Simon, T.M., 1990. Intraarticular Reaction Associated with the Use of Freeze-Dried, Ethylene Oxide-Sterilized Bone–Patella Tendon–Bone Allografts in the Reconstruction of the Anterior Cruciate Ligament. The American Journal of Sports Medicine, 18, 1–10.
  • Jackson, D.W., Grood, E.S., Cohn, B.T., Arnoczky, S.P., Simon, T.M., Cummings, J.F., 1991. The Effects of in Situ Freezing on the Anterior Cruciate Ligament. An Experimental Study in Goats. The Journal of Bone and Joint Surgery, 73, 201–213.
  • James, G.T., 1978. Inactivation of the Protease Inhibitor Phenylmethylsulfonyl Fluoride in Buffers. Anal Biochemistry, 86, 574-579.
  • Ketchedjian, A., Jones, A.L., Krueger, P., Robinson, E., Crouch, K., Wolfinbarger, L. Jr, Hopkins, R., 2005. Recellularization of Decellularized Allograft Scaffolds in Ovine Great Vessel Reconstructions. The Annals of Thoracic Surgery, 79(3), 888-896.
  • Klebe, R.J., 1974. Isolation of a Collagen-Dependent Cell Attachment Factor. Nature, 250, 248–51.
  • Khorramirouz, R., Sabetkish, S., Akbarzadeh, A., Muhammadnejad, A., Heidari, R., Kajbafzadeh, A.M., 2014. Effect of Three Decellularisation Protocols on the Mechanical Behaviour and Structural Properties of Sheep Aortic Valve Conduits. Advances in Medical Sciences, 59, 299-307.
  • Lee, R.C., 2005. Cell Injury by Electric Forces. Annals of the New York Academy of Sciences, 1066, 85–91.
  • Lin, P., Chan, W.C., Badylak, S.F., Bhatia, S.N., 2004. Assessing Porcine Liverderived Biomatrix For Hepatic Tissue Engineering. Tissue Engineering, 10, 1046–1053.
  • Mertsching, H., Walles, T., Hofmann, M., Schanz, J., Knapp W.H., 2005. Engineering Of A Vascularized Scaffold For Artificial Tissue And Organ Generation. Biomaterials, 26, 6610–6617
  • Petersen, T.H., Calle, E.A., Zhao, L., Lee, E.J., Gui, L., Raredon, M.B., Gavrilov, K., Yi, T., Zhuang, Z.W., Breuer, C., Herzog, E., Niklason, L.E., 2010. Tissue-Engineered Lungs for In Vivo İmplantation. Science (New York, NY), 329, 538–541.
  • Pruss, A., Kao, M., Kiesewetter, H., von Versen, R., Pauli, G., 1999. Virus Safety of Avital Bone Tissue Transplants: Evaluation of Sterilization Steps of Spongiosa Cuboids Using a Peracetic Acid–Methanol Mixture. Biologicals, 27, 195–201. Reing, J.E., Brown, B.N., Daly, K.A., Freund, J.M., Gilbert, T.W., Hsiong, S.X., Huber, A., Kullas, K.E., Tottey, S., Wolf, M.T., Badylak, S.F., 2010. The Effects of Processing Methods Upon Mechanical and Biologic Properties of Porcine Dermal Extracellular Matrix Scaffolds. Biomaterials, 31(33), 8626-8633.
  • Rieder, E., Kasimir, M.T., Silberhumer, G., Seebacher, G., Wolner, E., Simon, P., Weigel, G., 2004. Decellularization Protocols of Porcine Heart Valves Differ Importantly in Efficiency of Cell Removal and Susceptibility of the Matrix to Recellularization With Human Vascular Cells. The Journal of Thoracic and Cardiovascular Surgery, 127(2), 399-405.
  • Sasaki, M., Kleinman, H.K., Hubert, H., Deutzmann, R., Yamada, Y., 1988. Laminin, a Multidomain Protein. The Journal Of Biological Chemistry, 263(32), 16536-16544.
  • Schenke-Layland, K., Vasilevski, O., Opitz, F., Konig, K., Riemann, I., Halbhuber, K.J., Wahlers, T., Stock, U.A., 2003. Impact of Decellularization of Xenogeneic Tissue on Extracellular Matrix Integrity for Tissue Engineering of Heart Valves. Journal of Structural Biology, 143, 201–208.
  • Seddon, A.M., Curnow, P., Booth, P.J., 2004. Membrane Proteins, Lipids and Detergents: not Just a Soap Opera. Biochimica et Biophysica Acta, 1666, 105–117.
  • Şen, F., 2012. Matriks Metalloproteinaz-3 (MMP-3) ve Matriks Metalloproteinaz-9 (MMP-9) Gen Polimorfizminin Akut Miyokard İnfarktüsüne Olası Etkileri. Mersin Üniversitesi, Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı, Uzmanlık Tezi, 104 s., Mersin.
  • Teebken, O.E., Bader, A., Steinhoff, G., Haverich, A., 2000. Tissue Engineering of Vascular Grafts: Human Cell Seeding of Decellularised Porcine Matrix. European Journal of Vascular Endovascular Surgery, 19, 381–386.
  • Woods, T., Gratzer, P.F., 2005. Effectiveness of Three Extraction Techniques in the Development of a Decellularized Bone–Anterior Cruciate Ligament–Bone Graft. Biomaterials, 26, 7339–7349.
  • Wong, E.V., 2009. Cells: Molecules and Mechnisms. Axolotl Academic Publishing Company, 271 p., Louisville, Kentucky/USA.
  • Wilson,S.L., Sidney, L.E., Dunphy, S.E., Rose J.B., Hopkinson A., 2013. Keeping an Eye on Decellularized Corneas: A Review of Methods, Characterization and Applications. Biomater, 4, 114-161; doi:10.3390/jfb4030114 Xu, J., Mosher, D., 2011. Fibronectin and Other Adhesive Glycoproteins. The Extracellular Matrix: an Overview, Biology of Extracellular Matrix, Mecham, R. (Ed), 426, Springer-Verlag Berlin Heidelberg.
  • Xu, H., Xu, B., Yang, Q., Li, X., Ma, X., Xia, Q., Zhang, Y., Zhang, C., Wu, Y., Zhang, Y., 2014. Comparison of Decellularization Protocols for Preparing a Decellularized Porcine Annulus Fibrosus Scaffold. PloS One, 9, 1–13.
  • Xu, H., Wan, H., Sandor, M., Qi, S., Ervin, F., Harper, J.R., Silverman, R.P., McQuillan, D.J., 2008. Host Response to Human Acellular Dermal Matrix Transplantation in a Primate Model of Abdominal Wall Repair. Tissue Engineering Part A, 14(12), 2009-2019.
  • Voytik-Harbin, S.L., Brightman, A.O., Kraine, M.R., Waisner, B., Badylak, S.F., 1997. Identification of Extractable Growth Factors From Small Intestinal Submucosa. Journal of Cellular Biochemistry, 67, 478–491.
  • Vyavahare, N., Hirsch, D., Lerner, E., Baskin, J.Z., Schoen, F.J., Bianco, R., Kruth, H.S., Zand, R., Levy, R.J., 1997. Prevention of Bioprosthetic Heart Valve Calcification by Ethanol Preincubation. Efficacy and Mechanisms. Circulation, 95, 479–488.
  • Yang, B., Zhang, Y., Zhou, L., Sun, Z., Zheng, J., Chen, Y., Dai, Y., 2010. Development of a Porcine Bladder Acellular Matrix with Well-Preserved Extracellular Bioactive Factors for Tissue Engineering. Tissue Engineering: Part C, 16, 1201-1211.
  • Yang, X., Yuan, M.L., Li, W., Zhang, G.Y., 2004. Synthesis and Properties of Collagen/Polylactic Acid Blends. Journal of Applied Polymer Science, 94, 1670-1675
  • Yiğit, A., Yiğit, B., Koşar, Aslan, P., Savaş, H.B., Korkmaz, M., 2016. Doku Mühendisliğinde Deselülerizasyon Metotları ile Ekstraselüler Matriks (ECM) Eldesi ve Tıbbi Tedavide Uygulama Alanları. Kimya ve Sanayi Dergisi, 2(6), 29-43.
  • Yoo, J.J., Meng, J., Oberpenning, F., Atala A., 1998. Bladder Augmentation Using Allogenic Bladder Submucosa Seeded with Cells. Urology, 51, 221–225.
Toplam 75 adet kaynakça vardır.

Ayrıntılar

Konular Mühendislik
Bölüm TEKNİK BİLİMLER
Yazarlar

İbrahim Üçgül

Sultan Aras

Yayımlanma Tarihi 29 Aralık 2017
Kabul Tarihi 28 Kasım 2017
Yayımlandığı Sayı Yıl 2017 Cilt: 2 Sayı: 2

Kaynak Göster

APA Üçgül, İ., & Aras, S. (2017). DESELÜLERİZASYON YÖNTEMLERİ VE DOKULARDA KULLANIMI. Anka E-Dergi, 2(2), 19-34.
AMA Üçgül İ, Aras S. DESELÜLERİZASYON YÖNTEMLERİ VE DOKULARDA KULLANIMI. Anka E-Dergi. Aralık 2017;2(2):19-34.
Chicago Üçgül, İbrahim, ve Sultan Aras. “DESELÜLERİZASYON YÖNTEMLERİ VE DOKULARDA KULLANIMI”. Anka E-Dergi 2, sy. 2 (Aralık 2017): 19-34.
EndNote Üçgül İ, Aras S (01 Aralık 2017) DESELÜLERİZASYON YÖNTEMLERİ VE DOKULARDA KULLANIMI. Anka E-Dergi 2 2 19–34.
IEEE İ. Üçgül ve S. Aras, “DESELÜLERİZASYON YÖNTEMLERİ VE DOKULARDA KULLANIMI”, Anka E-Dergi, c. 2, sy. 2, ss. 19–34, 2017.
ISNAD Üçgül, İbrahim - Aras, Sultan. “DESELÜLERİZASYON YÖNTEMLERİ VE DOKULARDA KULLANIMI”. Anka E-Dergi 2/2 (Aralık 2017), 19-34.
JAMA Üçgül İ, Aras S. DESELÜLERİZASYON YÖNTEMLERİ VE DOKULARDA KULLANIMI. Anka E-Dergi. 2017;2:19–34.
MLA Üçgül, İbrahim ve Sultan Aras. “DESELÜLERİZASYON YÖNTEMLERİ VE DOKULARDA KULLANIMI”. Anka E-Dergi, c. 2, sy. 2, 2017, ss. 19-34.
Vancouver Üçgül İ, Aras S. DESELÜLERİZASYON YÖNTEMLERİ VE DOKULARDA KULLANIMI. Anka E-Dergi. 2017;2(2):19-34.