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DEVELOPMENT AND CHARACTERIZATION OF VITAMIN B9 - ELECTROSPRAYED NON-WOVEN SURFACES FOR WOUND HEALING APPLICATIONS

Yıl 2021, Cilt: 22 Sayı: Vol:22- 8th ULPAS - Special Issue 2021, 70 - 84, 30.11.2021
https://doi.org/10.18038/estubtda.983329

Öz

In this study, novel wound dressing materials based on non-woven (NW) surfaces were developed using electrospraying (e-spraying) process. Polyester spunbond (PET SPB), polypropylene spunbond (PP SPB), and polypropylene melt-blown (PP MB) surfaces used as matrix, and folic acid (FA), vitamin B9 were sprayed on these surfaces. The resulting NW fabrics with the same FA content were investigated in terms of chemical, morphological, thermal, wettability properties. Scanning Electron Microscopy and (SEM) and Fourier Transform Infrared (FT-IR) spectroscopy results showed formation of physical interaction between NWs and FA is successfully deposited onto NWs with average fiber diameters from 2.6 µm to 23.11 µm. According to the thermogravimetric analysis (TGA) FA loaded-PP SPB have enhaced thermal stability compared to pure one (PP SPB). The FA-loaded surfaces have hydrophobic property with contact angles values more than >90°. The in-vitro release was carried out by UV-Vis within the 8 hour-period phosphate buffer saline (pH 7.2). The results indicated that FA-loaded surfaces have a fast release behaviour. The total FA release amounts of the FA-loaded PET SBP, PP SPB and PP MB NWs were found as 22.8, 17.1, and 17.5 ppm. Moreover, biocompatibility of all resulting NW surfaces was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) cytotoxicity tests in L929 cell lines. The obtained NWs have biocompatible and non-toxic material except PET SPB-sFA.The study indicated that FA-loaded NWs can be potential candidates for wound healing applications.

Destekleyen Kurum

Bursa Technical University

Proje Numarası

190D003

Teşekkür

This study was supported by Bursa Technical University Scientific Research Projects Coordination Unit (SRP Project No. 190D003). The authors would like to thank Mogul Textile Company or their kind donation of spunbond and melt-blown non-woven fabrics and Bursa Technical University Central Research Laboratory (Bursa, Turkey) for the SEM and TGA analysis. The authors would like to thank Cantekin Kaykılarlı and Metallurgical and Materials Engineering Department for pycnometer test.

Kaynakça

  • [1] Hu MS, Maan ZN, Wu JC, Rennert RC, Hong WX. Tissue Engineering and Regenerative Repair in Wound Healing, Annals of Biomedical Engineering, 2014; 42: 1494-1507.
  • [2] Pakdemirli A, Toksöz F, Karadağ A, Mısırlıoğlu HK, Başbınar Y, Ellidokuz H, Açıkgöz O. Role of Mesenchymal Stem Cell-Derived Soluble Factors and Folic Acid in Wound Healing. Turk J Med Sci, 2019; 49: 914-921.
  • [3] Ammar HO, Ghorab MM, Mostafa DM, Ibrahim ES. Folic Acid Loaded Lipid Nanocarriers with Promoted Skin Antiaging and Antioxidant Efficacy, Journal of Drug Delivery Science and Technology, 2016; 31: 72-82.
  • [4] Jiao Z, Wang X, Yin Y, Xia J, Mei Y. Preparation and Evaluation of a Chitosan-Coated Antioxidant Liposome Containing Vitamin C and Folic Acid. Journal of Microencapsulation, 2018; 35(3): 272-280.
  • [5] Duman N, Duman R, Tosun M, Akıcı M, Göksel E, Gökçe B, Alagöz O. Topical Folinic Acid Enhances Wound Healing in Rat Model Advances in Medical Sciences, 2018; 63(2): 347-352.
  • [6] Parın FN, Aydemir İnci Ç, Taner G, Yıldırım K. Co-Electrospun-Electrosprayed PVA/Folic Acid Nanofibers for Transdermal Drug Delivery: Preparation, Characterization, and in vitro Cytocompatibility. Journal of Industrial Textiles, 2021; Doi: 10.1177/1528083721997185.
  • [7] Pagano C, Perioli L, Latterini L, Nocchetti M, Ceccarini MR, Marani M, Ramella D, Ricci M. Folic Acid-Layered Double Hydroxides Hybrids in Skin Formulations: Technological, Photochemical and in vitro Cytotoxicity on Human Keratinocytes and Fibroblasts. Applied Clay Science, 2019; 168: 382-395.
  • [8] Zhao M,Zhou J, Chen Y,Yuan L, Yuan M, Zhang X, Hu Y, Yu H. Folic Acid Promotes Wound Healing in Diabetic Mice by Suppression of Oxidative Stress, J Nutr Sci Vitamin, 2018; 64(1): 26-33.
  • [9] Khan S, Rahman SZ, Ahad A. Local Drug Delivery of Folic Acid Promotes Oral Mucosal Wound Healing. Journal of Dental Sciences, 2021; 16(1): 532-533.
  • [10] Camacho DH, Uy SJY, Cabrera MJF, Lobregas MOS, Fajardo TJMC. Encapsulation of Folic Acid in Copper-Alginate Hydrogels and It's Slow in vitro Release in Physiological pH Condition. Food Research International, 2019; 119: 15-22.
  • [11] Mallakpour S, HatamiM. Highly Capable and Cost-Effective Chitosan Nanocomposite Films Containing Folic Acid-Functionalized Layered Double Hydroxide and Their in Vitro Bioactivity Performance. Materials Chemistry and Physics2020;250:123044.
  • [12] Acevedo-Fani A, Soliva-Fortuny R, Martín-BellosoO. Photo-protection and Controlled Release of Folic Acid using Edible Alginate/Chitosan Nanolaminates. Journal of Food Engineering, 2018; 229:72-82
  • [13] Fonsecaa LM, Crizela RL, Silvaa FT, VazFontesa MR, Zavarezea ER, Guerra Dias AR. Starch Nanofibers as Vehicles for Folic Acid Supplementation: Thermal Treatment, UVA İrradiation, and in vitro Simulation of Digestion, Journal of the Science of Food and Agriculture, 2020; https://doi.org/10.1002/jsfa.10809.
  • [14] Şimşek M, Rzayev ZMO, Bunyatova U, Khalilova S, TürkM. Multifunctional Electrospun Biocompatible Nanofiber Composites from Water Dispersion Blends of Folic Acid Conjugated PVP/Dextran/ODA-MMT Nanocomposites and Their Responses to Vero cells. Hacettepe Journal of Biology and Chemistry, 2016; 44(4):441-450.
  • [15] Bock N, Dargaville TR,Woodruf MA. Electrospraying of Polymers with Therapeutic Molecules: State of The Art, Progress in Polymer Science, 2012; 37: 1510-1551.
  • [16] He L, Zhao Y, Tian L, Ramakrishna S. Nanobiomaterials: Classification, Fabrication and Biomedical Applications. I., Wang, M. Ramalingam, X. Kong, L. Zhao (Eds.), Electrospraying and Electrospinning for Nanobiomaterial Fabrication, 2017; (1st ed., Vol. 6, pp.143-163). New York : Wiley-VCH.
  • [17] Alehosseini A, Ghorani B, Sarabi-Jamab M, Tucker N. Principles of electrospraying: A New Approach in Protection of Bioactive Compounds in Foods. Critical Reviews in Food Science and Nutrition, 2017; 58(14): 2346-2363.
  • [18] Madhaiyan K, Sridhar R, Sundarrajan S, Venugopal JR, Ramakrishna S. Vitamin B12 Loaded Polycaprolactone Nanofibers: A Novel Transdermal Route for The Water Soluble Energy Supplement Delivery. International Journal of Pharmaceutics, 2013; 444(1-2): 70-76.
  • [19] Parın FN, Yıldırım K. Preparation and Characterization of Vitamin Loaded Electrospun Nanofibers as Promising Transdermal Patches. Fibres & Textiles in Eastern Europe, 2021; 1(145): 17-25.
  • [20] Ekabutr P, Chuysinuan P, Suksamrarn S, Sukhumsirichart W, Hongmanee P, Supaphol P. Development of Antituberculosis Melt-blown Polypropylene Filters Coated with Mangosteen Extracts for Medical Face Mask Applications. Polymer Bulletin, 2019; 76: 1985-2004.
  • [21] Jung JH, Lee JE, Bae G. Use of Electrosprayed Sophora Flavescens Natural-Product Nanoparticles for Antimicrobial air Filtration. Journal of Aerosol Science, 2013; 57: 185-193.
  • [22] Xiao X, Chen F, Wei Q, Wu N. Surface Modification of Polyester Nonwoven Fabrics by Al2O3 Sol–gel Coating, Journal of Coatings Technology and Research, 2009; 6(4): 537-541.
  • [23] Alma MH, Yazıcı M, Yıldırım B, Salan, T, Tiyek İ. Spunbond Dokusuz Tekstil Yüzeyi Üzerine Elektro Çekim Yöntemi ile Nano Boyutta Grafen Kaplanması ve Karakterizasyonu. Tekstil ve Mühendis, 2017; 24(108): 243-253.
  • [24] Delaviz Y, Santerre JP, Cvitkovitch DG. Infection Resistant Biomaterials, Biomaterials and Medical Device-Associated Infections, 2015; 11: 223-254.
  • [25] Berendjchi A, Ali R, Yousefi A, Yazdanshenas ME. Surface Characteristics of Coated Polyester Fabric with Reduced Graphene Oxide and Polypyrrole, Applied Surface Science, 2016; 367: 36-42.
  • [26] Ma ZW, Kotaki M, Yong T, He W, Ramakrishna S. Surface Engineering of Electrospun Polyethylene Terephthalate (PET) Nanofibers Towards Development of a New Material For Blood Vessel Engineering. Biomaterials, 2005; 26: 2527-2536.
  • [27] Sreedhara SS, Tata NR. A Novel Method for Measurement of Porosity in Nanofiber Mat using Pycnometer in Filtration. Journal of Engineered Fibers and Fabrics, 2013; 8(4).
  • [28] Gültekin E, Çelik Hİ, Nohut, S, Elma SK. Predicting Air Permeability and Porosity of Nonwovens with Image Processing and Artificial İntelligence Methods. The Journal of the Textile Institute, 2020; 111(11): 1641-1651.
  • [29] Weyermann J, Lochmann, D, Zimmer A. A Practicalnote on Theuse of Cytotoxicity Assays. International Journal of Pharmaceutics, 2005; 288 (2): 369-376.
  • [30] Melo PS, de Medeiros Cavalcante HM, Barbosa-Filho JM, de Fátima Formiga Melo Diniz M, de Medeiros IA, Haun M. Warifteine and Milonine, Alkaloids Isolated from Cissampe Lossympodialis Eichl: Cytotoxicity on Rathepatocyte Culture and in V79 Cells. Toxicology Letters, 2003; 142 (1-2):143-151.
  • [31] Arslan A, Şimşek M, Aldemir SD, Kazaroğlu NM, Gümüşderelioğlu, M. Honey-Based PET or PET/Chitosan Fibrous Wound Dressings: Effect of Honey on Electrospinning Process. Journal of Biomaterials Science, Polymer Edition, 2014; 25(10): 999-1012.
  • [32] Abouzekry S, Abdellatif A, Azzazy Hassan. Fabrication of Pomegranate/Honey Nanofibers for use As Antibacterial Wound Dressings. Wound Medicine, 2020; 28: 100181.
  • [33] Charernsriwilaiwat N, Opanasopit P, Rojanarata T, Ngawhirunpat T. Lysozyme-Loaded, Electrospun Chitosan-Based Nanofiber Mats for Wound Healing. International Journal of Pharmaceutics, 2012; 427(2): 379–384.
  • [34] Kalalinia F, Taherzadeh Z, Jirofti N, Amiri N, Foroghinia N, Beheshti M, Fazly B, Bibi S, Hashemi M, Shahroudi A, Pishavar E, Tabassi S, Movaffagh J. Evaluation of Wound Healing Efficiency of Vancomycin-Loaded Electrospun Chitosan/Poly Ethylene Oxide Nanofibers in Full Thickness Wound Model of Rat. International Journal of Biological Macromolecules, 2021; 177. 10.1016/j.ijbiomac.2021.01.209.
  • [35] Bayat S, Amiri N, Pishavar E, Kalalinia F, Movaffagh J, Hahsemi M. Bromelain-Loaded Chitosan Nanofibers Prepared by Electrospinning Method for Burn Wound Healing in Animal Models. Life Sciences, 2019; 229. 10.1016/j.lfs.2019.05.028.
  • [36] Merrell JG, McLaughlin SW, Tie L, Laurencin CT, Chen AF, Nair LS. Curcumin-loaded poly(epsilon-caprolactone) nanofibres: diabetic wound dressing with anti-oxidant and anti-inflammatory properties. Clinical and experimental pharmacology & Physiology, 2009; 36(12): 1149–1156.

DEVELOPMENT AND CHARACTERIZATION OF VITAMIN B9 - ELECTROSPRAYED NON-WOVEN SURFACES FOR WOUND HEALING APPLICATIONS

Yıl 2021, Cilt: 22 Sayı: Vol:22- 8th ULPAS - Special Issue 2021, 70 - 84, 30.11.2021
https://doi.org/10.18038/estubtda.983329

Öz

Proje Numarası

190D003

Kaynakça

  • [1] Hu MS, Maan ZN, Wu JC, Rennert RC, Hong WX. Tissue Engineering and Regenerative Repair in Wound Healing, Annals of Biomedical Engineering, 2014; 42: 1494-1507.
  • [2] Pakdemirli A, Toksöz F, Karadağ A, Mısırlıoğlu HK, Başbınar Y, Ellidokuz H, Açıkgöz O. Role of Mesenchymal Stem Cell-Derived Soluble Factors and Folic Acid in Wound Healing. Turk J Med Sci, 2019; 49: 914-921.
  • [3] Ammar HO, Ghorab MM, Mostafa DM, Ibrahim ES. Folic Acid Loaded Lipid Nanocarriers with Promoted Skin Antiaging and Antioxidant Efficacy, Journal of Drug Delivery Science and Technology, 2016; 31: 72-82.
  • [4] Jiao Z, Wang X, Yin Y, Xia J, Mei Y. Preparation and Evaluation of a Chitosan-Coated Antioxidant Liposome Containing Vitamin C and Folic Acid. Journal of Microencapsulation, 2018; 35(3): 272-280.
  • [5] Duman N, Duman R, Tosun M, Akıcı M, Göksel E, Gökçe B, Alagöz O. Topical Folinic Acid Enhances Wound Healing in Rat Model Advances in Medical Sciences, 2018; 63(2): 347-352.
  • [6] Parın FN, Aydemir İnci Ç, Taner G, Yıldırım K. Co-Electrospun-Electrosprayed PVA/Folic Acid Nanofibers for Transdermal Drug Delivery: Preparation, Characterization, and in vitro Cytocompatibility. Journal of Industrial Textiles, 2021; Doi: 10.1177/1528083721997185.
  • [7] Pagano C, Perioli L, Latterini L, Nocchetti M, Ceccarini MR, Marani M, Ramella D, Ricci M. Folic Acid-Layered Double Hydroxides Hybrids in Skin Formulations: Technological, Photochemical and in vitro Cytotoxicity on Human Keratinocytes and Fibroblasts. Applied Clay Science, 2019; 168: 382-395.
  • [8] Zhao M,Zhou J, Chen Y,Yuan L, Yuan M, Zhang X, Hu Y, Yu H. Folic Acid Promotes Wound Healing in Diabetic Mice by Suppression of Oxidative Stress, J Nutr Sci Vitamin, 2018; 64(1): 26-33.
  • [9] Khan S, Rahman SZ, Ahad A. Local Drug Delivery of Folic Acid Promotes Oral Mucosal Wound Healing. Journal of Dental Sciences, 2021; 16(1): 532-533.
  • [10] Camacho DH, Uy SJY, Cabrera MJF, Lobregas MOS, Fajardo TJMC. Encapsulation of Folic Acid in Copper-Alginate Hydrogels and It's Slow in vitro Release in Physiological pH Condition. Food Research International, 2019; 119: 15-22.
  • [11] Mallakpour S, HatamiM. Highly Capable and Cost-Effective Chitosan Nanocomposite Films Containing Folic Acid-Functionalized Layered Double Hydroxide and Their in Vitro Bioactivity Performance. Materials Chemistry and Physics2020;250:123044.
  • [12] Acevedo-Fani A, Soliva-Fortuny R, Martín-BellosoO. Photo-protection and Controlled Release of Folic Acid using Edible Alginate/Chitosan Nanolaminates. Journal of Food Engineering, 2018; 229:72-82
  • [13] Fonsecaa LM, Crizela RL, Silvaa FT, VazFontesa MR, Zavarezea ER, Guerra Dias AR. Starch Nanofibers as Vehicles for Folic Acid Supplementation: Thermal Treatment, UVA İrradiation, and in vitro Simulation of Digestion, Journal of the Science of Food and Agriculture, 2020; https://doi.org/10.1002/jsfa.10809.
  • [14] Şimşek M, Rzayev ZMO, Bunyatova U, Khalilova S, TürkM. Multifunctional Electrospun Biocompatible Nanofiber Composites from Water Dispersion Blends of Folic Acid Conjugated PVP/Dextran/ODA-MMT Nanocomposites and Their Responses to Vero cells. Hacettepe Journal of Biology and Chemistry, 2016; 44(4):441-450.
  • [15] Bock N, Dargaville TR,Woodruf MA. Electrospraying of Polymers with Therapeutic Molecules: State of The Art, Progress in Polymer Science, 2012; 37: 1510-1551.
  • [16] He L, Zhao Y, Tian L, Ramakrishna S. Nanobiomaterials: Classification, Fabrication and Biomedical Applications. I., Wang, M. Ramalingam, X. Kong, L. Zhao (Eds.), Electrospraying and Electrospinning for Nanobiomaterial Fabrication, 2017; (1st ed., Vol. 6, pp.143-163). New York : Wiley-VCH.
  • [17] Alehosseini A, Ghorani B, Sarabi-Jamab M, Tucker N. Principles of electrospraying: A New Approach in Protection of Bioactive Compounds in Foods. Critical Reviews in Food Science and Nutrition, 2017; 58(14): 2346-2363.
  • [18] Madhaiyan K, Sridhar R, Sundarrajan S, Venugopal JR, Ramakrishna S. Vitamin B12 Loaded Polycaprolactone Nanofibers: A Novel Transdermal Route for The Water Soluble Energy Supplement Delivery. International Journal of Pharmaceutics, 2013; 444(1-2): 70-76.
  • [19] Parın FN, Yıldırım K. Preparation and Characterization of Vitamin Loaded Electrospun Nanofibers as Promising Transdermal Patches. Fibres & Textiles in Eastern Europe, 2021; 1(145): 17-25.
  • [20] Ekabutr P, Chuysinuan P, Suksamrarn S, Sukhumsirichart W, Hongmanee P, Supaphol P. Development of Antituberculosis Melt-blown Polypropylene Filters Coated with Mangosteen Extracts for Medical Face Mask Applications. Polymer Bulletin, 2019; 76: 1985-2004.
  • [21] Jung JH, Lee JE, Bae G. Use of Electrosprayed Sophora Flavescens Natural-Product Nanoparticles for Antimicrobial air Filtration. Journal of Aerosol Science, 2013; 57: 185-193.
  • [22] Xiao X, Chen F, Wei Q, Wu N. Surface Modification of Polyester Nonwoven Fabrics by Al2O3 Sol–gel Coating, Journal of Coatings Technology and Research, 2009; 6(4): 537-541.
  • [23] Alma MH, Yazıcı M, Yıldırım B, Salan, T, Tiyek İ. Spunbond Dokusuz Tekstil Yüzeyi Üzerine Elektro Çekim Yöntemi ile Nano Boyutta Grafen Kaplanması ve Karakterizasyonu. Tekstil ve Mühendis, 2017; 24(108): 243-253.
  • [24] Delaviz Y, Santerre JP, Cvitkovitch DG. Infection Resistant Biomaterials, Biomaterials and Medical Device-Associated Infections, 2015; 11: 223-254.
  • [25] Berendjchi A, Ali R, Yousefi A, Yazdanshenas ME. Surface Characteristics of Coated Polyester Fabric with Reduced Graphene Oxide and Polypyrrole, Applied Surface Science, 2016; 367: 36-42.
  • [26] Ma ZW, Kotaki M, Yong T, He W, Ramakrishna S. Surface Engineering of Electrospun Polyethylene Terephthalate (PET) Nanofibers Towards Development of a New Material For Blood Vessel Engineering. Biomaterials, 2005; 26: 2527-2536.
  • [27] Sreedhara SS, Tata NR. A Novel Method for Measurement of Porosity in Nanofiber Mat using Pycnometer in Filtration. Journal of Engineered Fibers and Fabrics, 2013; 8(4).
  • [28] Gültekin E, Çelik Hİ, Nohut, S, Elma SK. Predicting Air Permeability and Porosity of Nonwovens with Image Processing and Artificial İntelligence Methods. The Journal of the Textile Institute, 2020; 111(11): 1641-1651.
  • [29] Weyermann J, Lochmann, D, Zimmer A. A Practicalnote on Theuse of Cytotoxicity Assays. International Journal of Pharmaceutics, 2005; 288 (2): 369-376.
  • [30] Melo PS, de Medeiros Cavalcante HM, Barbosa-Filho JM, de Fátima Formiga Melo Diniz M, de Medeiros IA, Haun M. Warifteine and Milonine, Alkaloids Isolated from Cissampe Lossympodialis Eichl: Cytotoxicity on Rathepatocyte Culture and in V79 Cells. Toxicology Letters, 2003; 142 (1-2):143-151.
  • [31] Arslan A, Şimşek M, Aldemir SD, Kazaroğlu NM, Gümüşderelioğlu, M. Honey-Based PET or PET/Chitosan Fibrous Wound Dressings: Effect of Honey on Electrospinning Process. Journal of Biomaterials Science, Polymer Edition, 2014; 25(10): 999-1012.
  • [32] Abouzekry S, Abdellatif A, Azzazy Hassan. Fabrication of Pomegranate/Honey Nanofibers for use As Antibacterial Wound Dressings. Wound Medicine, 2020; 28: 100181.
  • [33] Charernsriwilaiwat N, Opanasopit P, Rojanarata T, Ngawhirunpat T. Lysozyme-Loaded, Electrospun Chitosan-Based Nanofiber Mats for Wound Healing. International Journal of Pharmaceutics, 2012; 427(2): 379–384.
  • [34] Kalalinia F, Taherzadeh Z, Jirofti N, Amiri N, Foroghinia N, Beheshti M, Fazly B, Bibi S, Hashemi M, Shahroudi A, Pishavar E, Tabassi S, Movaffagh J. Evaluation of Wound Healing Efficiency of Vancomycin-Loaded Electrospun Chitosan/Poly Ethylene Oxide Nanofibers in Full Thickness Wound Model of Rat. International Journal of Biological Macromolecules, 2021; 177. 10.1016/j.ijbiomac.2021.01.209.
  • [35] Bayat S, Amiri N, Pishavar E, Kalalinia F, Movaffagh J, Hahsemi M. Bromelain-Loaded Chitosan Nanofibers Prepared by Electrospinning Method for Burn Wound Healing in Animal Models. Life Sciences, 2019; 229. 10.1016/j.lfs.2019.05.028.
  • [36] Merrell JG, McLaughlin SW, Tie L, Laurencin CT, Chen AF, Nair LS. Curcumin-loaded poly(epsilon-caprolactone) nanofibres: diabetic wound dressing with anti-oxidant and anti-inflammatory properties. Clinical and experimental pharmacology & Physiology, 2009; 36(12): 1149–1156.
Toplam 36 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Mühendislik
Bölüm Makaleler
Yazarlar

Fatma Nur Parın 0000-0003-2048-2951

Kenan Yıldırım 0000-0002-1640-6035

Gökçe Taner 0000-0002-0290-1166

Elife Kıldalı 0000-0003-0483-4363

Proje Numarası 190D003
Yayımlanma Tarihi 30 Kasım 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 22 Sayı: Vol:22- 8th ULPAS - Special Issue 2021

Kaynak Göster

AMA Parın FN, Yıldırım K, Taner G, Kıldalı E. DEVELOPMENT AND CHARACTERIZATION OF VITAMIN B9 - ELECTROSPRAYED NON-WOVEN SURFACES FOR WOUND HEALING APPLICATIONS. Eskişehir Technical University Journal of Science and Technology A - Applied Sciences and Engineering. Kasım 2021;22(Vol:22- 8th ULPAS - Special Issue 2021):70-84. doi:10.18038/estubtda.983329