Person: ŞAHİN, ALİ
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ŞAHİN
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ALİ
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Publication Open Access Controlled delivery of amoxicillin and rifampicin by three-dimensional polyvinyl alcohol/bismuth ferrite scaffolds(2023-05-01) ULAĞ, SONGÜL; ŞAHİN, ALİ; Ilgar S., ULAĞ S., ŞAHİN A., GÜNDÜZ O., Ustundag C. B.Skin is a protective barrier that can protect against environmental influences and renew itself. However, in some cases, this regenerative property is lost, and this causes delays in wound healing. Wound healing is a complex and long-lasting phase. Any bacterial infection during the wound healing process delays wound healing. The therapeutic efficacy can be increased by using nanocarrier drug delivery systems to the target tissue with modern wound dressings. Controlled nano drug delivery systems increase the therapeutic efficacy in the treatment of diseases and provide a faster recovery process. In this study, amoxicillin (AMX) and rifampicin (RIF) were loaded into the bismuth ferrite (BFO) particles which were synthesized with the co-precipitation method. Then, these drug-loaded BFO particles (0.075 %) were added separately to 13 % polyvinyl alcohol (PVA) solution and the solutions were printed three-dimensionally to obtain three dimensional scaffolds. With these designed scaffolds, it is aimed to reduce the risk of inflammation in wound tissues and increase therapeutic efficacy with controlled release. The SEM images proved that homogeneous pore distributions could be achieved with these combinations. The tensile test results showed that drug-loaded BFO addition increased the mechanical strength of the 13 % PVA scaffold. The biocompatibility test results demonstrated that the highest viability values of the human adipose tissue-derived mesenchymal stem cells were obtained for AMX-added 13 % PVA scaffolds.Publication Open Access Fabrication of gentamicin sulfate-loaded 3d-printed polyvinyl alcohol/sodium alginate/gelatin-methacryloyl hybrid scaffolds for skin tissue replacement(2023-01-01) ULAĞ, SONGÜL; ŞAHİN, ALİ; AKSU, MEHMET BURAK; GÜNDÜZ, OĞUZHAN; Izgordu M. S., Ayran M., ULAĞ S., Yildirim R., Bulut B., ŞAHİN A., Guncu M. M., AKSU M. B., GÜNDÜZ O.3D-printed scaffolds can better mimic the function of human skin, both biologically and mechanically. Within the scope of this study, the effect of the addition of different amounts (10, 15, 20 mg) of gentamicin sulfate (GS) to a 10 mL solution of natural and synthetic polymers is investigated. Sodium alginate (SA), gelatin-methacryloyl (GelMA), and polyvinyl alcohol (PVA) are chosen as bioactive materials. The surface morphology and pore structures are visualized by scanning electron microscopy (SEM). According to the results, it is observed that the pore sizes of all scaffolds are smaller than 270 µm, the lowest value (130 µm) is obtained in the scaffold loaded with 15 mg GS, and it also has the highest tensile strength value (12.5 ± 7.6 MPa). Similarly, it is observed that the tensile strength (9.7 ± 4.5 MPa) is high in scaffold loaded with 20 mg GS. The biocompatibility test is performed with fibroblast cells, and the results show that the scaffolds are biocompatible with cells. The antibacterial test is carried out against the S.aureous and E. coli and the results indicate that all GS-loaded scaffolds demonstrate antibacterial activity.Publication Open Access Production and characterization of PLA/HA/GO nanocomposite scaffold(2022-08-12) ŞAHİN, ALİ; GÜNDÜZ, OĞUZHAN; Oktay B., Ahlatcıoğlu Özerol E., Şahin A., Gunduz O., Ustundag C. B.© 2022 Wiley-VCH GmbH.Polylactic acid (PLA) composite nanofibers combined with hydroxyapatite (HA) and graphene oxide (GO) nanoparticles were produced by electrospinning to create excellent biodegradable and durable scaffolds to be used in tissue engineering. The properties of the pure PLA, PLA/HA, PLA/GO, and PLA/HA/GO nanocomposite scaffolds were analyzed in chemical, morphological, mechanical, and biocompatibility. Morphology and composition were investigated by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), respectively. To predict the cytocompatibility of these scaffolds, HFF-1 cells were cultured and the respective cell adhesion and proliferation were investigated by fluorescence microscopy, SEM, and MTT assay. FTIR results showed the successful synthesis of HA and GO nanoparticles. SEM images showed that the PLA/HA/GO scaffold is ideal for cell attachment and proliferation in tissue regeneration. Mechanical test results showed that the tensile strength and elastic modulus of PLA nanofibers could be increased by adding 0,8 wt % HA and 0,4 wt % GO. The PLA/HA/GO scaffold exhibited the highest tensile strength of other scaffolds. MTT assay revealed that the PLA/HA/GO scaffold showed significantly high biocompatibility with 105 % cell viability. Therefore, PLA/HA/GO scaffold with 0,8 wt %HA and 0,4 wt %GO possessing high tensile strength as well as good cell proliferation is an excellent and versatile biomaterial for tissue engineering applications.Publication Open Access Dual spinneret electrospun polyurethane/pva-gelatin nanofibrous scaffolds containing cinnamon essential oil and nanoceria for chronic diabetic wound healing: preparation, physicochemical characterization and in-vitro evaluation(2022-04-01) ŞAHİN, ALİ; GÜNDÜZ, OĞUZHAN; Hussein M. A. M., Gunduz O., Sahin A., Grinholc M., El-Sherbiny I. M., Megahed M.© 2022 by the authors. Licensee MDPI, Basel, Switzerland.In this study, a dual spinneret electrospinning technique was applied to fabricate a series of polyurethane (PU) and polyvinyl alcohol–gelatin (PVA/Gel) nanofibrous scaffolds. The study aims to enhance the properties of PU/PVA-Gel NFs loaded with a low dose of nanoceria through the incorporation of cinnamon essential oil (CEO). The as-prepared nCeO2 were embedded into the PVA/Gel nanofibrous layer, where the cinnamon essential oil (CEO) was incorporated into the PU nanofibrous layer. The morphology, thermal stability, mechanical properties, and chemical composition of the produced NF mats were investigated by STEM, DSC, and FTIR. The obtained results showed improvement in the mechanical, and thermal stability of the dual-fiber scaffolds by adding CEO along with nanoceria. The cytotoxicity evaluation revealed that the incorporation of CEO to PU/PVA-Gel loaded with a low dose of nanoceria could enhance the cell population compared to using pure PU/PVA-Gel NFs. Moreover, the presence of CEO could inhibit the growth rate of S. aureus more than E. coli. To our knowledge, this is the first time such nanofibrous membranes composed of PU and PVA-Gel have been produced. The first time was to load the nanofibrous membranes with both CEO and nCeO2. The obtained results indicate that the proposed PU/PVA-Gel NFs represent promising platforms with CEO and nCeO2 for effectively managing diabetic wounds.Publication Open Access Fabrication of electrospun juglans regia (juglone) loaded poly(lactic acid) scaffolds as a potential wound dressing material(2022-05-01) ALTAN, ERAY; ŞAHİN, ALİ; GÜNDÜZ, OĞUZHAN; ULAĞ, SONGÜL; ALTAN E., Karacelebi Y., Saatcioglu E., ULAĞ S., ŞAHİN A., AKSU M. B., Croitoru A., Codrea C. I., Ficai D., GÜNDÜZ O., et al.Juglone (5-hydroxy-1,4-naphthoquinone) (J) is a naphthoquinone structured allelochemical that is mostly found in the roots, leaves, nut-hulls, bark, and wood of walnut (Juglans regia). In this study, the biocompatibility, mechanical, thermal, chemical, morphological, and antimicrobial properties of the poly(lactic acid) (PLA) (w/v)/J (10, 20, 30 mg) electrospun scaffolds were investigated. Based on the results of the study, it was shown that juglone addition increased the antimicrobial properties of the scaffolds against the Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the neat PLA film after 24 h of contact time. According to the tensile test results, the addition of J made the scaffolds more flexible but decreased the mechanical strength. The cytotoxicity properties of the J-added scaffolds demonstrated a toxic behavior on the first day of incubation. However, with an increase in the J ratio, the fibroblast cell metabolic activity increased for all incubation periods.Publication Metadata only Combination of second-generation proteasome inhibitor carfilzomib with bortezomib in four different breast cancer cell lin(2022-01-01) YILMAZ GÖLER, AYŞE MİNE; ŞAHİN, ALİ; YILMAZ, BETÜL; Altundag E. M., Yilmaz A. M., Sahin A., Yilmaz B.Background: Proteasome inhibitors target different pathways in cells and therefore are promising drugs in cancer therapy. The use of these inhibitors is approved mainly in hematological cancers, and recently many clinical trials and preclinical studies have been conducted on efficacy in solid tumors. Carfilzomib is a second-generation inhibitor and was developed to decrease the side effects of bortezomib. Although there are many valid therapies for breast cancer, resistance and recurrence are inevitable in many cases and the proteasomal system plays an important role in related pathways. Objective: This study is a preliminary work to evaluate the combined effects of bortezomib and carfilzomib in four different breast cancer cells. Methods: MDA-MB-231, MCF-7, UACC-2087, and SKBR-3 cell lines were used. Cell viability was determined using bortezomib and carfilzomib alone and in combination. Combination effect values were determined using the Chou-Talalay method. Apoptosis, proteasome activity, cleaved PARP, and HSP70 expressions were analyzed in the determined doses. Results: The response to the combination of the two inhibitors was different in four cell lines. Apoptosis was significantly higher in combination groups compared to carfilzomib in three cell lines except for SKBR-3, and higher in the combination group compared to bortezomib only in UACC-2087. Combination decreased cleaved PARP levels in MDA-MB-231 and MCF-7 and increased SKBR-3 compared to bortezomib. HSP70 levels decreased in combination with UACC-2087 and SKBR-3 compared to carfilzomib. Conclusion: Taken together, the combination of the two inhibitors was more apoptotic compared to carfilzomib and apoptosis was higher only in UACC-2087 compared to bortezomib. This apoptosis data can not be directly correlated to the degree of proteasome inhibition, PARP cleavage, and HSP70 response.Publication Open Access Co-axial electrospinning of liposomal propolis loaded gelatin-zein fibers as a potential wound healing material(2023-01-01) ŞAHİN, ALİ; Karakas C. Y., ÜSTÜNDAĞ C. B., ŞAHİN A., KARADAĞ A.In this study, propolis extract (PE) was first encapsulated in different liposomal formulations (65–370 nm) with high encapsulation efficiency (68%–93%). The liposomal PE was further embedded in a food-grade gelatin-zein core/shell fiber by using the co-axial electrospinning method. Transmission electron and confocal laser scanning microscopy verified the structure of liposomes and their homogeneous dispersion in fibers. Scanning electron microscopy (SEM) images confirmed the smooth morphologies of core/shell liposomal fibers. The loading of PE in liposomal fibers improved both thermal (differential scanning calorimetry) and textural (elongation at break and tensile strength) properties, and the fibers loaded with more PE provided higher mucoadhesiveness. The PE-loaded fiber showed higher antimicrobial activity against Staphylococcus aureus. The incorporation of liposomal PE in fiber enhanced the viability of human skin fibroblast (HFF-1) cells. The adhesion of HFF-1 cells on fiber was demonstrated by SEM, thus PE-loaded liposomal fiber could provide an efficient platform for cell growth. The findings of this study proposed that propolis-loaded liposomal hybrid fibers produced by the co-axial method can be used as a potential wound healing material.Publication Open Access Gentamicin-loaded polyvinyl alcohol/whey protein isolate/hydroxyapatite 3D composite scaffolds with drug delivery capability for bone tissue engineering applications(2022-10-05) ŞAHİN, ALİ; GÜNDÜZ, OĞUZHAN; Tut T. A. , Cesur S., Ilhan E., ŞAHİN A., Yildirim O. S. , GÜNDÜZ O.Bone defects caused by diseases such as bone diseases, tumours, and traumas negatively affect the lives of millions of people around the world. Bone tissue engineering offers a new approach to repairing bone defects. Here, a novel bioactive Polyvinyl alcohol (PVA)/ Whey protein isolate (WPI)/ Hydroxyapatite (HA) composite scaffolds with Gentamicin (GEN)-loaded at varying rates were successfully fabricated by 3D printing technology. The strong interaction between PVA, WPI, HA, and GEN were proved with Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). When the scanning electron microscopy (SEM) images of the produced 3D composite scaffolds were evaluated, it can be said that 3D composite scaffolds with the desired porosity and structure for bone tissue engineering applications were obtained. The 3D PVA/WPI/HA/12GEN composite scaffold was fabricated excellently with its 675 μm pore size. Compression tests revealed that the 3D composite scaffold had a compressive strength of 1.28–1.22 MPa and strain of % 12.89–8.70 and thus met the mechanical desirables of human trabecular bone. Moreover, the compressive strength and strain values of the scaffolds were decreased slightly due to adding the GEN drug. According to the Differential scanning calorimetry (DSC) analysis, it was determined that the highly crystalline structure of PVA was disrupted by adding GEN to the composite scaffolds. It was also observed that the addition of GEN to the scaffold did not significantly affect the swelling and degradation behaviour, and the scaffolds degraded by approximately 55% on the 10th day. The scaffolds exhibited a controlled release profile up to 240 and 264 h and were released with the Korsmeyer-Peppas kinetic model according to the highest correlation number. Cell analysis revealed that biocompatible structures were produced, and osteoblasts formed filopodia extensions, resulting in healthy cell attachment. According to these results, 3D GEN-loaded PVA/WPI/HA composite scaffolds may be a promising innovation for bone defect repair in bone tissue engineering applications.Publication Open Access Production of 3D Printed Bi-Layer and Tri-Layer Sandwich Scaffolds with Polycaprolactone and Poly (vinyl alcohol)-Metformin towards Diabetic Wound Healing(2022-12-01) ŞAHİN, ALİ; Harmanci S., Dutta A., Cesur S., Sahin A., Gunduz O., Kalaskar D. M., Ustundag C. B.Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by impaired insulin secretion, sensitivity, and hyperglycemia. Diabetic wounds are one of the significant complications of T2DM owing to its difficulty in normal healing, resulting in chronic wounds. In the present work, PCL/PVA, PCL/PVA/PCL, and metformin-loaded, PCL/PVA-Met and PCL/PVA-Met/PCL hybrid scaffolds with different designs were fabricated using 3D printing. The porosity and morphological analysis of 3D-printed scaffolds were performed using scanning electron microscopy (SEM). The scaffolds’ average pore sizes were between 63.6 ± 4.0 and 112.9 ± 3.0 µm. Molecular and chemical interactions between polymers and the drug were investigated with Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Mechanical, thermal, and degradation analysis of the scaffolds were undertaken to investigate the physico-chemical characteristics of the scaffolds. Owing to the structure, PCL/PVA/PCL sandwich scaffolds had lower degradation rates than the bi-layer scaffolds. The drug release of the metformin-loaded scaffolds was evaluated with UV spectrometry, and the biocompatibility of the scaffolds on fibroblast cells was determined by cell culture analysis. The drug release in the PCL/PVA-Met scaffold was sustained till six days, whereas in the PCL/PVA-Met/PCL, it continued for 31 days. In the study of drug release kinetics, PCL/PVAMet and PCL/PVA-Met/PCL scaffolds showed the highest correlation coefficients (R2 ) values for the first-order release model at 0.8735 and 0.889, respectively. Since the layered structures in the literature are mainly obtained with the electrospun fiber structures, these biocompatible sandwich scaffolds, produced for the first time with 3D-printing technology, may offer an alternative to existing drug delivery systems and may be a promising candidate for enhancing diabetic wound healing.Publication Open Access Single-Walled (Magnetic) Carbon Nanotubes in a Pectin Matrix in the Design of an Allantoin Delivery System(2023-01-01) BATIREL, SAİME; ŞAHİN, ALİ; Güner Yılmaz Ö. Z., Yılmaz A., Bozoglu S., Yavuz N., BATIREL S., ŞAHİN A., Güner F. S.Single-walled carbon nanotubes (SWCNTs) outperform other materials due to their high conductivity, large specific surface area, and chemical resistance. They have numerous biomedical applications, including the magnetization of the SWCNT (mSWCNT). The drug loading and release properties of see-through pectin hydrogels doped with SWCNTs and mSWCNTs were evaluated in this study. The active molecule in the hydrogel structure is allantoin, and calcium chloride serves as a cross-linker. In addition to mixing, absorption, and swelling techniques, drug loading into carbon nanotubes was also been studied. To characterize the films, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, surface contact angle measurements, and opacity analysis were carried out. Apart from these, a rheological analysis was also carried out to examine the flow properties of the hydrogels. The study was also expanded to include N-(9-fluorenyl methoxycarbonyl)glycine-coated SWCNTs and mSWCNTs as additives to evaluate the efficiency of the drug-loading approach. Although the CNT additive was used at a 1:1000 weight ratio, it had a significant impact on the hydrogel properties. This effect, which was first observed in the thermal properties, was confirmed in rheological analyses by increasing solution viscosity. Additionally, rheological analysis and drug release profiles show that the type of additive causes a change in the matrix structure. According to TGA findings, even though SWCNTs and mSWCNTs were not coated more than 5%, the coating had a significant effect on drug release control. In addition to all findings, cell viability tests revealed that hydrogels with various additives could be used for visual wound monitoring, hyperthermia treatment, and allantoin release in wound treatment applications.