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Öğe Çift Tabakalı Fıtık Yaması: In-Vitro Ve In-Vivo Karakterizasyon(2022) Demirbilek, Murat; Öcal, Berrak Gümüşkaya; Türkoğlu, Nelisa; Aydın, Oktay; Türk, MustafaKarın içi yapışıklıklar, bantlar periton hasarına karşı inflamatuar bir yanıttır. Fıtık abdominal cerrahide %2- 20 oranında görülmektedir. Bununla birlikte abdominal cerrahi sonrasında %90 peritoneal yapışma görülmektedir. Fıtık bir yama ile kapatılabilir. Yama olarak degrede olmayan malzemeler sıklıkla kullanılmaktadır. Bununla birlikte nüks riskini azaltması, enfekte hastalarda kullanabilirliği degrede olan yamaların kullanımının önünü açmıştır. Sunulan proje raporunda çift tabakalı, degrede olan, modifiye polihidroksibutirat-ko-hezanoat (PHBHX) yamalar hazırlanmıştır. PHBHX yamalar film formunda üretilmiştir. Yamaların karın duvarına yapışmasını sağlamak için, karın duvarı yönünde şeker bazlı adezif bir jel kullanılmıştır. Yamaların karın duvarı yönünde ise, adezyonu engellemek için PHBHX oleik asit, miristik asit, polietilen glikol 400, polietilen glikol 8000 ile modifiye edilmiştir. Yamaların termal ve fiziksel özellikleri, homojenitesi, yüzey yükü, yüzey % polar etkileşim değeri belirlenmiştir. Aynı zamanda yamaların insan serum albümin bağlama kapasitesi, kan pıhtılaşma faktörlerine etkisi, mutajenitesi belirlenmiştir. Yapılan çalışmalar sonucunda PEG 400 ile modifikasyonun yamaların mekanik özelliklerini ve degredasyon süresini düşürdüğü belirlenmiştir. Miristik asit modifiye formülasyonların polistren hücre kültür kabına yapıştığı görülmüştür. Oleik asitin kan pıhtılaşma zamanını uzattığı belirlenmiştir. PEG 8000 modifikasyonunun yamaların mekanik özelliklerini ve termal stabiliteyi artırdığı saptanmıştır. Bu nedenlerden dolayı PHBHX, PHBHXPEG83, PHBHXOA yama formülasyonları belirlenmiş ve projenin ilerleyen basamaklarında kullanılmıştır. Belirlenen formülasyonlara sahip çift tabakalı yamalar işlevselliği sıçan fıtık modelinde test edilmiştir. Sıçanların karın duvarlarında bir cm eninde üç cm uzunluğunda defekt oluşturulmuş ve yamalar karın duvarına süturlanmıştır. Operasyonlardan 21 gün sonra operasyon bölgeleri açılmıştır. Operasyon bölgesi makroskobik olarak incelenmiş ve skorlanmıştır. Fıtık hattında proinflamatuar sitokinlerin seviyesi, oksidatif-antioksidan moleküllerin seviyesi belirlenmiştir. Kolajen tip 1, inflamasyon, skar doku ve vaskülerizasyon histolojik yöntemlerle incelenmiştir. İn vivo sonuçlar incelendiğinde oleik asit modifikasyonunun adezif bant sayısını, inflamasyonu ve skar dokuyu artırdığı görülmüştür. Buna karşın PEG 8000 modifikasyonun adezif bantların sayısını, skar dokuyu azalttığı görülmüştür. PEG 8000 modifiye yamanın karın duvarı iyileşirken yapışık dokuları birbirinden ayırdığı ve bant oluşumunu engelliğine karar verilmiştir.Öğe Dual delivery of platelet-derived growth factor and bone morphogenetic factor-6 on titanium surface to enhance the early period of implant osseointegration(WILEY, 2020) Keceli, H. Gencay; Bayram, Cem; Celik, Ekin; Ercan, Nuray; Demirbilek, Murat; Nohutcu, Rahime MeralObjective To test the surface properties and in vitro effects of a new sequential release system on MC3T3-E1 cells for improved osseointegration. Background BMP6-loaded anodized titanium coated with PDGF containing silk fibroin (SF) may improve osseointegration. Methods Titanium surfaces were electrochemically anodized, and SF layer was covered via electrospinning. Five experimental groups (unanodized Ti (Ti), anodized Ti (AnTi), anodized + BMP6-loaded Ti (AnTi-BMP6), anodized + BMP6 loaded + silk fibroin-coated Ti (AnTi-BMP6-SF), and anodized + BMP6-loaded + silk fibroin with PDGF-coated Ti (AnTi-BMP6-PDGF-SF)) were tested. After SEM characterization, contact angle analysis, and FTIR analysis, the amount of released PDGF and BMP6 was detected using ELISA. Cell proliferation (XTT), mineralization, and gene expression (RUNX2andALPL) were also evaluated. Results After successful anodization and loading of PDGF and BMP6, contact angle measurements showed hydrophobicity for TiO(2)and hydrophilicity for protein-adsorbed surfaces. In FTIR, protein-containing surfaces exhibited amide-I, amide-II, and amide-III bands at 1600 cm(-1)-1700 cm(-1), 1520 cm(-1)-1540 cm(-1), and 1220 cm(-1)-1300 cm(-1)spectrum levels with a significant peak in BMP6- and/or SF-loaded groups at 1100 cm(-1). PDGF release and BMP6 release were delayed, and relatively slower release was detected in SF-coated surfaces. Higher MC3T3-E1 proliferation and mineralization and lower gene expression ofRUNX2andALPLwere detected in AnTi-BMP6-PDGF-SF toward day 28. Conclusion The new system revealed a high potential for an improved early osseointegration period by means of a better factor release curve and contribution to the osteoblastic cell proliferation, mineralization, and associated gene expression.Öğe In vitro comparison of nanofibrillar and macroporous-spongious composite tissue scaffolds for periodontal tissue engineering(Taylor and Francis Ltd., 2022) Şahbazoğlu, Kemal Burak; Demirbilek, Murat; Bayarı, Sevgi Haman; Buber, Esra; Toklucu, Selçuk; Türk, Mustafa; Karabulut, ErdemPurpose/Aim of the study: The ultimate goal of periodontal treatment is to regenerate the lost periodontal tissues. The interest in nanomaterials in dentistry is growing rapidly and has focused on improvements in various biomedical applications, such as periodontal regeneration and periodontal tissue engineering. To enhance periodontal tissue regeneration, hydroxyapatite (HA) was used in conjunction with other scaffold materials, such as Poly lactic-co-glycolic-acid (PLGA) and collagen (C). The main target of this study was to compare the effects of nano and macrostructures of the tissue scaffolds on cell behavior in vitro for periodontal tissue engineering. Materials and Methods: Nanofibrillar and macroporous-spongious composite tissue scaffolds were produced using PLGA/C/HA. Subgroups with BMP-2 signal molecule and without HA were also created. The scaffolds were characterized by FTIR, SEM/EDX techniques, and mechanical tests. The scaffolds were compared in the periodontal ligament (PDL) and MCT3-E1 cell cultures. The cell behaviors; adhesions by SEM, proliferation by WST-1, differentiation by ALP and mineralization with Alizarin Red Tests were determined. Results: Cell adhesion and mineralization were higher in the nanofibrillar scaffolds compared to the macroporous-spongious scaffolds. Macroporous-spongious scaffolds seemed better for the proliferation of PDL cells and differentiation of MC3T3-E1-preosteoblastic cells, while nanofibrillar scaffolds were more convenient for the differentiation of PDL cells and proliferation of MC3T3-E1-preosteoblastic cells. Conclusions: In general, nanofibrillar scaffolds showed more favorable results in cell behaviors, compared to the macroporous-spongious scaffolds, and mostly, BMP-2 and HA promoted the activities of the cells. © 2021 Informa UK Limited, trading as Taylor & Francis Group.Öğe In vitro comparison of nanofibrillar and macroporous-spongious composite tissue scaffolds for periodontal tissue engineering(Taylor & Francis Inc, 2022) Sahbazoglu, Kemal Burak; Demirbilek, Murat; Bayari, Sevgi Haman; Buber, Esra; Toklucu, Selcuk; Turk, Mustafa; Karabulut, ErdemPurpose/Aim of the study: The ultimate goal of periodontal treatment is to regenerate the lost periodontal tissues. The interest in nanomaterials in dentistry is growing rapidly and has focused on improvements in various biomedical applications, such as periodontal regeneration and periodontal tissue engineering. To enhance periodontal tissue regeneration, hydroxyapatite (HA) was used in conjunction with other scaffold materials, such as Poly lactic-co-glycolic-acid (PLGA) and collagen (C). The main target of this study was to compare the effects of nano and macrostructures of the tissue scaffolds on cell behavior in vitro for periodontal tissue engineering. Materials and Methods: Nanofibrillar and macroporous-spongious composite tissue scaffolds were produced using PLGA/C/HA. Subgroups with BMP-2 signal molecule and without HA were also created. The scaffolds were characterized by FTIR, SEM/EDX techniques, and mechanical tests. The scaffolds were compared in the periodontal ligament (PDL) and MCT3-E1 cell cultures. The cell behaviors; adhesions by SEM, proliferation by WST-1, differentiation by ALP and mineralization with Alizarin Red Tests were determined. Results: Cell adhesion and mineralization were higher in the nanofibrillar scaffolds compared to the macroporous-spongious scaffolds. Macroporous-spongious scaffolds seemed better for the proliferation of PDL cells and differentiation of MC3T3-E1-preosteoblastic cells, while nanofibrillar scaffolds were more convenient for the differentiation of PDL cells and proliferation of MC3T3-E1-preosteoblastic cells. Conclusions: In general, nanofibrillar scaffolds showed more favorable results in cell behaviors, compared to the macroporous-spongious scaffolds, and mostly, BMP-2 and HA promoted the activities of the cells.Öğe Preparation and characterization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHX) based nanoparticles for targeted cancer therapy(Elsevier Science Bv, 2011) Kilicay, Ebru; Demirbilek, Murat; Turk, Mustafa; Guven, Eylem; Hazer, Baki; Denkbas, Emir BakiTargeted drug delivery systems are one of the most promising alternatives for the cancer therapy. Rapid developments on nanomedicine facilitated the creation of novel nanotherapeutics by using different nanomaterials. Especially polymer based nanoparticles are convenient for this purpose. In this study; a natural polymer (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate), PHBHHX) was used as a base matrix for the production of a novel nanotherapeutic including antineoplastic agent, Etoposide and attached folic acid as a ligand on the nanoparticles. Modified solvent evaporation technique was used for the production of PHBHHX nanoparticles and the average size of the obtained PHBHHX nanoparticles were observed in the range of 180 nm and 1.5 mu m by the change in experimental conditions (i.e., homogenization rate, surfactant concentration and polymer/solvent ratio). By the increase in homogenization rate and surfactant concentration, size of the nanoparticles was decreased, while the size was increased by the increase in polymer/solvent ratio. Drug loading ratio was also found to be highly affected by polymer/drug ratio. Surface charge of the prepared nanoparticles was also investigated by zeta potential measurements. In the cytotoxicity tests; Etoposide loaded and folic acid attached PHBHHX nanoparticles were observed as more effective on HeLa cells than Etoposide loaded PHBHHX nanoparticles without attached folic acid. The cytotoxicity of folic acid conjugated PHBHHX nanoparticles to cancer cells was found to be much higher than that of normal fibroblast cells, demonstrating that the folate conjugated nanoparticles has the ability to selectively target to cancer cells. In addition, apoptotic/necrotic activities were evaluated for all formulations of the PHBHHX nanoparticles and parallel results with cytotoxicity tests were obtained. These studies demonstrate that the folic acid attached and Etoposide loaded PHBHHX nanoparticles seem as promising for the targeted cancer therapy. (C) 2011 Elsevier B.V. All rights reserved.Öğe Targeted delivery of etoposide to osteosarcoma cells using poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles(Tubitak Scientific & Technical Research Council Turkey, 2017) Alp, Esma; Cirak, Tamer; Demirbilek, Murat; Turk, Mustafa; Guven, EylemFolic acid (FA)-functionalized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles were prepared to enhance the delivery efficiency of the anticancer drug etoposide for the clinical treatment of osteosarcoma. PHBV nanoparticles were synthesized by emulsification/solvent evaporation technique and obtained in the size range of 200-250 nm and zeta potential range of -21 and -27 mV. Encapsulation efficiency and in vitro drug release were studied. The cytotoxic, apoptotic, and necrotic effects of PHBV nanoparticles were also investigated using Saos-2 osteosarcoma cells. The results obtained in this study demonstrate that etoposide-loaded and FA-functionalized PHBV nanoparticles can be successfully used for targeted treatment of osteosarcoma.
