Research Article
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The Preparation and Characterization of Electrospun PCL/PHBV Membranes as Wound Dressing Material

Year 2019, Volume: 8 Issue: 3, 1029 - 1044, 30.09.2019
https://doi.org/10.17798/bitlisfen.530767

Abstract





















In this study, fibrous
membranes of Polycaprolactone (PCL), Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)
(PHBV) and PCL/PHBV blends in different weight ratios (100:0, 50:50, 75:25,
0:100) were prepared using different solvents (chloroform (CHCl3),
1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP) and their blends) via electrospinning
technique as wound dressing materials. Structural, morphological, and thermal
characterizations of membranes were performed by Fourier Transform Infrared
Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM) and Differential
Scanning Calorimetry (DSC), respectively. Moreover, the water-uptake capacity
of the membranes were analyzed using absorption test. Following that, human
fibroblast cells were seeded on the selected membranes and in vitro cell viability and toxicity were monitored by MTT assay
for 24, 48 and 72th hours.  The
seeded cell proliferation on membranes was conducted for 36, 72 and 120th
hours and the results were examined by SEM. The results of this study relieved
that electrospun PCL/PHBV (75:25) blend membrane solved in HFIP can be used as
wound dressing materials.
    

References

  • 1. Kuppan, P., Kirthanashri S.V., Dhakshinamoorthy S., Uma M.K., and Swaminathan S. 2011. Development of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Fibers for Skin Tissue Engineering: Effects of Topography, Mechanical, and Chemical Stimuli, Biomacromolecules, 12 (9): 3156–3165.
  • 2. Zonari, A., Cerqueira M.T., Novikoff, S., Goes A.M., Marques, A.P., Correlo, V.M. and Reis, R.L. 2014. Poly(hydroxybutyrate-co-hydroxyvalerate) Bilayer Skin Tissue Engineering Constructs with Improved Epidermal Rearrangement, Macromolecular Bioscience, 14 (7): 977–990.
  • 3. Du, L., Xu, H.Z., Li, T., Zhang, Y. and Zou, F.Y. 2017. Fabrication of Ascorbyl Palmitate Loaded Poly(caprolactone)/Silver Nanoparticle Embedded Poly(vinyl alcohol) Hybrid Nanofibre Mats as Active Wound Dressings: Via Dual-Spinneret Electrospinning, RSC Advances, 7 (50): 31310–31318.
  • 4. Augustine R., Anto Dominic E., Reju I., Kaimal B., Kalarikkal N., Thomas S. 2015. Electrospun Poly(e-caprolactone)-Based Skin Substitutes: In Vivo Evaluation of Wound Healing and The Mechanism of Cell Proliferation, Journal of Biomedical Materials Research Part B: Applied Biomaterials, 103 (7): 1445–1454.
  • 5. Sahana, T.G., Rekha, P.D. 2018. Biopolymers: Applications in Wound Healing and Skin Tissue Engineering, Molecular Biology Report, 45 (6): 2857-2867.
  • 6. Moura D., Souza M.T., Liverani L., Rella G., Luz G.M., Mano J.F., Boccaccini A.R. 2017. Development of A Bioactive Glass-Polymer Composite for Wound Healing Applications, Materials Science and Engineering C, 76: 224-232.
  • 7. Sundaramurthi D., Krishnan U.M., Sethuraman S. 2014. Epidermal Differentiation of Stem Cells on Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) Nanofibers, Annals of Biomedical Engineering, 42 (12): 2589–2599.
  • 8. Lee J.M., Chae T., Sheikh F.A., Ju H.W., Moon B.M., Park H.J., Park Y.R., Park C.H. 2016. Three Dimensional Poly(ε-caprolactone) and Silk Fibroin Nanocomposite Fibrous Matrix for artificial Dermis, Materials Science and Engineering: C, 68: 758–67.
  • 9. MacEwan M.R., Macewan S., Kovacs T.R., Batts J. 2017. What Makes the Optimal Wound Healing Material? A Review of Current Science and Introduction of a Synthetic Nanofabricated Wound Care Scaffold. 9 (10), 1736-1748.
  • 10. Biazar E. 2017. Application of Polymeric Nanofibers in Medical Designs, Part I: Skin and Eye, International Journal of Polymeric Materials and Polymeric Biomaterials, 66 (10): 521–531.
  • 11. Miguel S.P., Figueira D.R., Simões D., Ribeiro M.P., Coutinho P., Ferreira P., Correia I.J. 2018. Electrospun Polymeric Nanofibres as Wound Dressings: A Review, Colloids Surfaces B Biointerfaces, 169: 60–71.
  • 12. Lv F., Wang J., Xu P., Han Y., Ma H., Xu H., Chen S., Chang J., Ke Q., Liu M., Yi Z., Wu C. 2017. A Conducive Bioceramic/Polymer Composite Biomaterial for Diabetic Wound Healing, Acta Biomaterialia, 60: 128–143.
  • 13. Bölgen N., Menceloǧlu Y.Z., Acatay K., Vargel I., Pişkin E. 2005 In Vitro and In Vivo Degradation of Non-Woven Materials Made of Poly(Ε-Caprolactone) Nanofibers Prepared by Electrospinning Under Different Conditions. Journal of Biomaterials Science, Polymer Edition, 16 (12): 1537–1555.
  • 14. Rather H.A., Thakore R., Singh R., Jhala D., Singh S., Vasita R. Antioxidative Study of Cerium Oxide Nanoparticle Functionalised PCL-Gelatin Electrospun Fibers for Wound Healing Application, Bioactive Materials, 3 (2): 201–211.
  • 15. Yuan J., Geng J., Xing Z., Shim K-J., Han I., Kim J-C., Kang I-K., Shen J. 2015. Novel Wound Dressing Based on Nanofibrous PHBV–Keratin Mats, Journal of Tissue Engineering and Regenerative Medicine, 9: 1027–1035.
  • 16. Tohidi S., Ghaee A., Barzin J. 2016, Preparation and Characterization of Poly(lactic-co-glycolic acid)/Chitosan Electrospun Membrane Containing Amoxicillin-Loaded Halloysite Nanoclay, Polymers for Advanced Technologies, 27: 1020-1028.
  • 17. Dias J.R., Granja P.L., Bártolo P.J. 2016. Advances in Electrospun Skin Substitutes, Progress in Materials Science, 84: 314-334.
  • 18. Zhang W., Ronca S., Mele E. 2017. Electrospun Nanofibres Containing Antimicrobial Plant Extracts, Nanomaterials, 7 (2): 42-59.
  • 19. Patil J.V., Mali S.S., Kamble A.S., Hong C.K., Kim J.H., Patil P.S. 2017. Electrospinning: a Versatile Technique for Making of 1D Growth of Nanostructured Nanofibers and Its Applications: An Experimental Approach. Applied Surface Science, 423: 641–674.
  • 20. Chen S., Liu B., Carlson M.A., Gombart A.F., Reilly D.A., Xie J. 2017. Recent Advances in Electrospun Nanofibers for Wound Healing, Nanomedicine, 12: 1335-1352.
  • 21. Liu M., Duan X., Li Y., Yang D., Long Y. 2017. Electrospun Nano Fibers for Wound Healing, Materials Science and Engineering C, 76: 1413-1423.
  • 22. Mir M., Ali M.N., Barakullah A., Gulzar A., Arshad M, Fatima S., Asad M. 2018. Synthetic Polymeric Biomaterials for Wound Healing: A Review, Progress in Biomaterials, 7 (1): 1-21.
  • 23. Siddiqui N., Asawa S., Birru B., Baadhe R., Rao S. 2018. PCL-Based Composite Scaffold Matrices for Tissue Engineering Applications. Molecular Biotechnology, 60: 506–532.
  • 24. Thanh Tra N., Minh H.H., Nam T.M.H., Thien D.B.T., Hoai, N.T.T., Phuoc, T.V., Thai D.M., Hai, N.D., Toi, V.V., Hiep, N.T. 2018. Optimization and Characterization of Electrospun Polycaprolactone Coated with Gelatin-Silver Nanoparticles for Wound Healing Application, Materials Science & Engineering C, 91: 318-329.
  • 25. Martins A.F., Facchi S.P., da Câmara P.C.F., Camargo S.E.A., Camargo C.H.R., Popat K.C., Kipper M.J. 2018. Novel Poly(ε-Caprolactone)/Amino-Functionalized Tannin Electrospun Membranes as Scaffolds for Tissue Engineering, Journal of Colloid and Interface Science, 525: 21-30.
  • 26. Mutlu G., Calamak S., Ulubayram K., Guven E. 2018. Curcumin-Loaded Electrospun PHBV Nanofibers as Potential Wound-Dressing Material, Journal of Drug Delivery Science and Technology, 43: 185-193.
  • 27. Veleirinho B., Coelho D.S., Dias P.F., Maraschin M., Ribeiro-do-Valle R.M., Lopes-da-Silva J.A. 2012. Nanofibrous Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Chitosan Scaffolds for Skin Regeneration. International Journal of Biological Macromolecules, 51 (4): 343-350.
  • 28. Shishatskaya E.I., Nikolaeva E.D., Vinogradova O.N., Volova T.G. 2016. Experimental Wound Dressings of Degradable PHA for Skin Defect Repair, Journal of Materials Science: Materials in Medicine, 27 (11): 165.
  • 29. Adeli-Sardou M., Yaghoobi M.M., Torkzadeh-Mahani M., Dodel M. 2019. Controlled Release of Lawsone from Polycaprolactone/Gelatin Electrospun Nano Fibers for Skin Tissue Regeneration, International Journal of Biological Macromolecules, 124: 478-491.
  • 30. Ehterami A., Salehi M., Farzamfar S., Vaez A., Samadian H., Sahrapeyma H., Mirzaii M., Ghorbani S., Goodarzi A. 2018. In Vitro and In Vivo Study of PCL/COLL Wound Dressing Loaded with Insulin-Chitosan Nanoparticles on Cutaneous Wound Healing in Rats Model, International Journal of Biological Macromolecules, 117: 601-609.
  • 31. İşoğlu İ.A., Demirkan C., Şeker M.G., Tuzlakoğlu K., İşoğlu S.D. 2018. Antibacterial Bilayered Skin Patches Made of HPMA and Quaternary Poly(4-Vinyl Pyridine). Fibers and Polymers, 19 (11): 2229-2236.
  • 32. K-Hasuwan P.R., Pavasant P., Supaphol P. 2011. Effect of the Surface Topography of Electrospun Poly(ε-caprolactone)/Poly(3-hydroxybuterate-co-3-hydroxyvalerate) Fibrous Substrates on Cultured Bone Cell Behavior. Langmuir. 27: 10938-10946.
  • 33. Malikmammadov E., Tanir T.E., Kiziltay A., Hasirci V., Hasirci N. 2018. PCL and PCL-Based Materials in Biomedical Applications, Journal of Biomaterials Science, Polymer Edition, 29 (7-9): 863-893.
  • 34. Del Gaudio C., Ercolani E., Nanni F., Bianco A. 2011. Assessment of Poly(ε-caprolactone)/Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Blends Processed by Solvent Casting and Electrospinning, Materials Science and Engineering A, 528 (3): 1764-1772.
  • 35. Chanda A., Adhikari J., Ghosh A., Roy S., Thomas S., Datta P., Saha P. 2018. Electrospun Chitosan/Polycaprolactone-Hyaluronic Acid Bilayered Scaffold for Potential Wound Healing Applications, International Journal of Biological Macromolecules, 116: 774-785.

Yara Örtü Malzemesi Olarak Elektroeğrilmiş PCL/PHBV Membranların Hazırlanması ve Karakterizasyonu

Year 2019, Volume: 8 Issue: 3, 1029 - 1044, 30.09.2019
https://doi.org/10.17798/bitlisfen.530767

Abstract

Bu çalışmada, yara örtü malzemesi olarak polikaprolakton (PCL), poli(3-hidroksibütirik asit-ko-3-hidroksivalerik asit) (PHBV) ve ağırlıkça farklı oranlarda (100:0, 50:50, 75:25, 0:100) PCL/PHBV karışımları, farklı çözücüler (kloroform (CHCl3), 1,1,1,3,3,3-Hexfluoro-2-propanol (HFIP) ve bunların karışımları) kullanılarak elektroeğirme tekniği ile fibroz yapıda membranlar hazırlanmıştır. Tüm elektroeğrilmiş membranlar Fourier Dönüşümlü Kızılötesi Spektroskopisi (FT-IR), Diferansiyel Taramalı Kalorimetre (DSC) ve Taramalı Elektron Mikroskobu (SEM) ile yapı, morfoloji ve ısıl özellikleri açısından karakterize edilmiştir. Ayrıca, absorbsiyon testi ile sıvı tutma kapasiteleri analiz edilmiştir. Karakterizasyon basamağından sonra, seçilen membranların üzerine insan fibroblast hücreleri ekilmiş, in vitro hücre canlılık ve toksisite, MTT testi ile 24, 48 ve 72. saat için analiz edilmiştir. Membranların üzerine ekilen hücrelerin çoğalması 36, 72 ve 120. saat olmak üzere 3 farklı süre için incelenmiş, sonuçlar SEM ile gösterilmiştir. Elde edilen sonuçlar PCL/PHBV (75:25) karışım ile HFIP çözeltisinde elektroeğrilen membranın yara örtü malzemesi olarak kullanılabileceğini göstermiştir.

References

  • 1. Kuppan, P., Kirthanashri S.V., Dhakshinamoorthy S., Uma M.K., and Swaminathan S. 2011. Development of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Fibers for Skin Tissue Engineering: Effects of Topography, Mechanical, and Chemical Stimuli, Biomacromolecules, 12 (9): 3156–3165.
  • 2. Zonari, A., Cerqueira M.T., Novikoff, S., Goes A.M., Marques, A.P., Correlo, V.M. and Reis, R.L. 2014. Poly(hydroxybutyrate-co-hydroxyvalerate) Bilayer Skin Tissue Engineering Constructs with Improved Epidermal Rearrangement, Macromolecular Bioscience, 14 (7): 977–990.
  • 3. Du, L., Xu, H.Z., Li, T., Zhang, Y. and Zou, F.Y. 2017. Fabrication of Ascorbyl Palmitate Loaded Poly(caprolactone)/Silver Nanoparticle Embedded Poly(vinyl alcohol) Hybrid Nanofibre Mats as Active Wound Dressings: Via Dual-Spinneret Electrospinning, RSC Advances, 7 (50): 31310–31318.
  • 4. Augustine R., Anto Dominic E., Reju I., Kaimal B., Kalarikkal N., Thomas S. 2015. Electrospun Poly(e-caprolactone)-Based Skin Substitutes: In Vivo Evaluation of Wound Healing and The Mechanism of Cell Proliferation, Journal of Biomedical Materials Research Part B: Applied Biomaterials, 103 (7): 1445–1454.
  • 5. Sahana, T.G., Rekha, P.D. 2018. Biopolymers: Applications in Wound Healing and Skin Tissue Engineering, Molecular Biology Report, 45 (6): 2857-2867.
  • 6. Moura D., Souza M.T., Liverani L., Rella G., Luz G.M., Mano J.F., Boccaccini A.R. 2017. Development of A Bioactive Glass-Polymer Composite for Wound Healing Applications, Materials Science and Engineering C, 76: 224-232.
  • 7. Sundaramurthi D., Krishnan U.M., Sethuraman S. 2014. Epidermal Differentiation of Stem Cells on Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) Nanofibers, Annals of Biomedical Engineering, 42 (12): 2589–2599.
  • 8. Lee J.M., Chae T., Sheikh F.A., Ju H.W., Moon B.M., Park H.J., Park Y.R., Park C.H. 2016. Three Dimensional Poly(ε-caprolactone) and Silk Fibroin Nanocomposite Fibrous Matrix for artificial Dermis, Materials Science and Engineering: C, 68: 758–67.
  • 9. MacEwan M.R., Macewan S., Kovacs T.R., Batts J. 2017. What Makes the Optimal Wound Healing Material? A Review of Current Science and Introduction of a Synthetic Nanofabricated Wound Care Scaffold. 9 (10), 1736-1748.
  • 10. Biazar E. 2017. Application of Polymeric Nanofibers in Medical Designs, Part I: Skin and Eye, International Journal of Polymeric Materials and Polymeric Biomaterials, 66 (10): 521–531.
  • 11. Miguel S.P., Figueira D.R., Simões D., Ribeiro M.P., Coutinho P., Ferreira P., Correia I.J. 2018. Electrospun Polymeric Nanofibres as Wound Dressings: A Review, Colloids Surfaces B Biointerfaces, 169: 60–71.
  • 12. Lv F., Wang J., Xu P., Han Y., Ma H., Xu H., Chen S., Chang J., Ke Q., Liu M., Yi Z., Wu C. 2017. A Conducive Bioceramic/Polymer Composite Biomaterial for Diabetic Wound Healing, Acta Biomaterialia, 60: 128–143.
  • 13. Bölgen N., Menceloǧlu Y.Z., Acatay K., Vargel I., Pişkin E. 2005 In Vitro and In Vivo Degradation of Non-Woven Materials Made of Poly(Ε-Caprolactone) Nanofibers Prepared by Electrospinning Under Different Conditions. Journal of Biomaterials Science, Polymer Edition, 16 (12): 1537–1555.
  • 14. Rather H.A., Thakore R., Singh R., Jhala D., Singh S., Vasita R. Antioxidative Study of Cerium Oxide Nanoparticle Functionalised PCL-Gelatin Electrospun Fibers for Wound Healing Application, Bioactive Materials, 3 (2): 201–211.
  • 15. Yuan J., Geng J., Xing Z., Shim K-J., Han I., Kim J-C., Kang I-K., Shen J. 2015. Novel Wound Dressing Based on Nanofibrous PHBV–Keratin Mats, Journal of Tissue Engineering and Regenerative Medicine, 9: 1027–1035.
  • 16. Tohidi S., Ghaee A., Barzin J. 2016, Preparation and Characterization of Poly(lactic-co-glycolic acid)/Chitosan Electrospun Membrane Containing Amoxicillin-Loaded Halloysite Nanoclay, Polymers for Advanced Technologies, 27: 1020-1028.
  • 17. Dias J.R., Granja P.L., Bártolo P.J. 2016. Advances in Electrospun Skin Substitutes, Progress in Materials Science, 84: 314-334.
  • 18. Zhang W., Ronca S., Mele E. 2017. Electrospun Nanofibres Containing Antimicrobial Plant Extracts, Nanomaterials, 7 (2): 42-59.
  • 19. Patil J.V., Mali S.S., Kamble A.S., Hong C.K., Kim J.H., Patil P.S. 2017. Electrospinning: a Versatile Technique for Making of 1D Growth of Nanostructured Nanofibers and Its Applications: An Experimental Approach. Applied Surface Science, 423: 641–674.
  • 20. Chen S., Liu B., Carlson M.A., Gombart A.F., Reilly D.A., Xie J. 2017. Recent Advances in Electrospun Nanofibers for Wound Healing, Nanomedicine, 12: 1335-1352.
  • 21. Liu M., Duan X., Li Y., Yang D., Long Y. 2017. Electrospun Nano Fibers for Wound Healing, Materials Science and Engineering C, 76: 1413-1423.
  • 22. Mir M., Ali M.N., Barakullah A., Gulzar A., Arshad M, Fatima S., Asad M. 2018. Synthetic Polymeric Biomaterials for Wound Healing: A Review, Progress in Biomaterials, 7 (1): 1-21.
  • 23. Siddiqui N., Asawa S., Birru B., Baadhe R., Rao S. 2018. PCL-Based Composite Scaffold Matrices for Tissue Engineering Applications. Molecular Biotechnology, 60: 506–532.
  • 24. Thanh Tra N., Minh H.H., Nam T.M.H., Thien D.B.T., Hoai, N.T.T., Phuoc, T.V., Thai D.M., Hai, N.D., Toi, V.V., Hiep, N.T. 2018. Optimization and Characterization of Electrospun Polycaprolactone Coated with Gelatin-Silver Nanoparticles for Wound Healing Application, Materials Science & Engineering C, 91: 318-329.
  • 25. Martins A.F., Facchi S.P., da Câmara P.C.F., Camargo S.E.A., Camargo C.H.R., Popat K.C., Kipper M.J. 2018. Novel Poly(ε-Caprolactone)/Amino-Functionalized Tannin Electrospun Membranes as Scaffolds for Tissue Engineering, Journal of Colloid and Interface Science, 525: 21-30.
  • 26. Mutlu G., Calamak S., Ulubayram K., Guven E. 2018. Curcumin-Loaded Electrospun PHBV Nanofibers as Potential Wound-Dressing Material, Journal of Drug Delivery Science and Technology, 43: 185-193.
  • 27. Veleirinho B., Coelho D.S., Dias P.F., Maraschin M., Ribeiro-do-Valle R.M., Lopes-da-Silva J.A. 2012. Nanofibrous Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Chitosan Scaffolds for Skin Regeneration. International Journal of Biological Macromolecules, 51 (4): 343-350.
  • 28. Shishatskaya E.I., Nikolaeva E.D., Vinogradova O.N., Volova T.G. 2016. Experimental Wound Dressings of Degradable PHA for Skin Defect Repair, Journal of Materials Science: Materials in Medicine, 27 (11): 165.
  • 29. Adeli-Sardou M., Yaghoobi M.M., Torkzadeh-Mahani M., Dodel M. 2019. Controlled Release of Lawsone from Polycaprolactone/Gelatin Electrospun Nano Fibers for Skin Tissue Regeneration, International Journal of Biological Macromolecules, 124: 478-491.
  • 30. Ehterami A., Salehi M., Farzamfar S., Vaez A., Samadian H., Sahrapeyma H., Mirzaii M., Ghorbani S., Goodarzi A. 2018. In Vitro and In Vivo Study of PCL/COLL Wound Dressing Loaded with Insulin-Chitosan Nanoparticles on Cutaneous Wound Healing in Rats Model, International Journal of Biological Macromolecules, 117: 601-609.
  • 31. İşoğlu İ.A., Demirkan C., Şeker M.G., Tuzlakoğlu K., İşoğlu S.D. 2018. Antibacterial Bilayered Skin Patches Made of HPMA and Quaternary Poly(4-Vinyl Pyridine). Fibers and Polymers, 19 (11): 2229-2236.
  • 32. K-Hasuwan P.R., Pavasant P., Supaphol P. 2011. Effect of the Surface Topography of Electrospun Poly(ε-caprolactone)/Poly(3-hydroxybuterate-co-3-hydroxyvalerate) Fibrous Substrates on Cultured Bone Cell Behavior. Langmuir. 27: 10938-10946.
  • 33. Malikmammadov E., Tanir T.E., Kiziltay A., Hasirci V., Hasirci N. 2018. PCL and PCL-Based Materials in Biomedical Applications, Journal of Biomaterials Science, Polymer Edition, 29 (7-9): 863-893.
  • 34. Del Gaudio C., Ercolani E., Nanni F., Bianco A. 2011. Assessment of Poly(ε-caprolactone)/Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Blends Processed by Solvent Casting and Electrospinning, Materials Science and Engineering A, 528 (3): 1764-1772.
  • 35. Chanda A., Adhikari J., Ghosh A., Roy S., Thomas S., Datta P., Saha P. 2018. Electrospun Chitosan/Polycaprolactone-Hyaluronic Acid Bilayered Scaffold for Potential Wound Healing Applications, International Journal of Biological Macromolecules, 116: 774-785.
There are 35 citations in total.

Details

Primary Language Turkish
Journal Section Araştırma Makalesi
Authors

İsmail Alper İşoğlu 0000-0001-6428-4207

Publication Date September 30, 2019
Submission Date February 22, 2019
Acceptance Date July 1, 2019
Published in Issue Year 2019 Volume: 8 Issue: 3

Cite

IEEE İ. A. İşoğlu, “Yara Örtü Malzemesi Olarak Elektroeğrilmiş PCL/PHBV Membranların Hazırlanması ve Karakterizasyonu”, Bitlis Eren Üniversitesi Fen Bilimleri Dergisi, vol. 8, no. 3, pp. 1029–1044, 2019, doi: 10.17798/bitlisfen.530767.

Bitlis Eren University
Journal of Science Editor
Bitlis Eren University Graduate Institute
Bes Minare Mah. Ahmet Eren Bulvari, Merkez Kampus, 13000 BITLIS