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    A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber
    (Shenyang Pharmaceutical Univ, 2024) Ercelik, Melis; Tekin, Cagla; Gurbuz, Melisa; Tuncbilekli, Yagmur; Dogan, Hazal Yilmaz; Mutlu, Busra; Tunca, Berrin
    Total resection of glioblastoma (GB) tumors is nearly impossible, and systemic administration of temozolomide (TMZ) is often inadequate. This study presents a hybrid layered composite nanofiber mesh (LHN) designed for localized treatment in GB tumor bed. The LHN, consisting of polyvinyl alcohol and core-shell polylactic acid layers, was loaded with TMZ and rutin. In vitro analysis revealed that LHNTMZ and LHNrutin decelerated epithelial-mesenchymal transition and growth of stem-like cells, while the combination, LHNTMZ+rutin, significantly reduced sphere size compared to untreated and LHNTMZ-treated cells (P < 0.0001). In an orthotopic C6-induced GB rat model, LHNTMZ+rutin therapy demonstrated a more pronounced tumor-reducing effect than LHNTMZ alone. Tumor volume, assessed by magnetic resonance imaging, was significantly reduced in LHNTMZ+rutin-treated rats compared to untreated controls. Structural changes in tumor mitochondria, reduced membrane potential, and decreased PARP expression indicated the activation of apoptotic pathways in tumor cells, which was further confirmed by a reduction in PHH3, indicating decreased mitotic activity of tumor cells. Additionally, the local application of LHNs in the GB model mitigated aggressive tumor features without causing local tissue inflammation or adverse systemic effects. This was evidenced by a decrease in the angiogenesis marker CD31, the absence of inflammation or necrosis in H&E staining of the cerebellum, increased production of IFN-gamma, decreased levels of interleukin-4 in splenic T cells, and lower serum AST levels. Our findings collectively indicate that LHNTMZ+rutin is a promising biocompatible model for the local treatment of GB. (c) 2024 Shenyang Pharmaceutical University. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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    Assessing the effects of boron-doped biphasic calcium phosphate on the characteristics of chitosan-based composite foams
    (Springer, 2025) Acar, Nurcan; Mutlu, Busra; Akben, Hatice Kubra; Duman, Seyma
    In this study, composite foams containing chitosan (CHI) and boron doped-biphasic calcium phosphate (BCP) were developed using freeze-drying method. The quantities of BCP incorporated into the CHI matrix were introduced into the foams at three different ratios: 25 wt%, 50 wt%, and 75 wt%. The objective of this study was to investigate the microstructure, swelling, mechanical, and biological properties of boron-doped BCP/CHI-based composites. Scanning electron microscopy (SEM) micrographs revealed that all of the composites exhibited open and interconnected pore morphologies. The FTIR spectra demonstrated that boron doping interacts with the hydroxyl and phosphate groups in the CHI/BCP composites, which is evidenced by changes in peak intensities. It was found that low amounts of boron positively affected the compressive strength and in vitro cytotoxicity of the composites. Following simulated body fluid treatment, the boron-doped BCP/CHI composites exhibited robust apatite layer formation. These results indicated that the composite foams with modified physical and mechanical characteristics show considerable promise for use as composite materials in biomedical applications, including bone scaffolds or wound dressings.
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    Curcumin-Loaded Akermanite/Chitosan/Carboxymethylcellulose Patches for Skin Wound Healing: Fabrication, Characterization, and In Vitro Cytocompatibility
    (Wiley-V C H Verlag Gmbh, 2025) Mutlu, Busra; Demirci, Fatma; Ercelik, Melis; Tekin, Cagla; Tunca, Berrin; Terzioglu, Pinar; Duman, Seyma
    In this study, bioactive and biocompatible transdermal patches were fabricated through the lyophilization of a chitosan/carboxymethylcellulose/akermanite composite matrix. The influence of curcumin incorporation at 0.5%, 1%, and 2% on the physicochemical, morphological, and biological properties of the patches was systematically investigated. Scanning electron microscopy revealed an interconnected porous structure with pore sizes ranging from 29 to 57 mu m, facilitating cell infiltration and nutrient transport. Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy confirmed the successful integration of akermanite and curcumin, along with characteristic interactions within the polymeric network. In vitro release studies demonstrated a biphasic profile consisting of an initial burst followed by a sustained release phase, with the CCMAKCur0.5 sample achieving the highest cumulative release (94.28%). Antioxidant performance, evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method, ranged from 21.55% (CCM) to 38.96% (CCMAKCur0.5), while higher curcumin concentrations reduced activity due to increased matrix densification. Simulated body fluid immersion confirmed apatite formation, particularly in CCMAKCur0.5 and CCMAKCur2, indicating enhanced bioactivity. Cytocompatibility studies with HUVECs showed no toxic effects, and scratch assays demonstrated that CCMAKCur0.5 most effectively promoted wound closure. Overall, the findings indicate that curcumin- and akermanite-loaded lyophilized patches represent promising candidates for transdermal therapeutic applications.
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    In Vitro Behavior of Boron-Doped Baghdadite/Poly(vinylidene fluoride) Membrane Scaffolds Produced via Non-Solvent Induced Phase Separation
    (Wiley-V C H Verlag Gmbh, 2025) Mutlu, Busra; Demirci, Fatma; Erginer, Merve; Duman, Seyma
    This study explores the potential of boron-doped baghdadite (BAG) powders incorporated into poly(vinylidene fluoride) (PVDF)-based membrane scaffolds for bone tissue engineering applications. The aim is to enhance the scaffolds' microstructure, surface wettability, thermal behavior, mechanical properties, and biological performance. Composite scaffolds are fabricated by integrating the powders into the PVDF matrix, yielding scaffolds with enhanced material characteristics and functionality. The incorporation of the powders significantly enhances the hydrophilicity of the scaffolds, as evidenced by a notable reduction in contact angle measurements. Mechanical analyses demonstrate that the addition of boron-doped BAG powders reduces the tensile strength and elongation at the break of PVDF scaffolds, attribute to increased pore size, reduced crystallinity, and structural heterogeneity, though the values remain within the range of human cancellous bone. Furthermore, in vitro bioactivity studies reveal the superior apatite-forming ability of the composite scaffolds, indicating their enhanced potential for biomineralization. The results of the cellular adhesion assays indicate an enhanced affinity and proliferation of cells on the membrane scaffolds, which is indicative of improved biocompatibility. In conclusion, the developed PVDF-based membrane scaffolds, reinforce with BAG powders, show promise as effective alternatives to traditional bone graft materials, offering scalable and versatile solutions for regenerative medicine.
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    Incorporation of cerium oxide into hydroxyapatite/chitosan composite scaffolds for bone repair
    (Univ Novi Sad, Fac Technology, 2022) Mutlu, Busra; Caylak, Sena; Duman, Seyma
    This study reports on the production of chitosan-based composite scaffolds reinforced with hydroxyapatite (HA) powders prepared with cerium oxide (CeO2) with various concentrations (10, 20, 30 wt.%). Besides, the effect of CeO2 additive on the microstructural, mechanical and bioactivity properties of the composite scaffolds was investigated. The CeO2 reinforced HA powders were synthesized having homogenous particle distribution via spray drying process. The synthesized powders and the produced scaffolds were examined using different characterization methods. From the results, it can be seen that the scaffolds were significantly affected by amount of CeO2 additive. An increase in the compressive strength is observed as the amount of CeO2 additive rises. Furthermore, the composite scaffolds possessed a high mineralization ability of apatite in simulated body fluid (SBF). These observations related to the composite scaffolds have considerable potency for application in bone tissue engineering.
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    Incorporatıon of carob pod powder on polyvınyl alcohol-based bıocomposıte hydrogel fılm
    (Springer, 2025) Mutlu, Busra; Eroglu, Murat
    Carob pod powder (CP), a neglected agro-waste material, provides a sustainable, cheap substitute for synthetic fillers, meeting the global demand for eco-friendly materials. In this context, this study investigates the incorporation of CP into polyvinyl alcohol (PVA)-based biocomposite hydrogel films to enhance their mechanical, structural, physicochemical, physical, and optical properties. The hydrogel films were prepared by dissolving PVA in distilled water, followed by the addition of CP powder at varying concentrations (5%, 10%, and 20% by weight). The mixtures were crosslinked using 6 M NaOH solution. Characterization of the prepared hydrogel samples was carried out by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), mechanical and optical testing. The results showed the addition of CP powder considerably improves the tensile strength and elongation at break of the hydrogel films, being most effective at 10% CP concentration. Hydrogel samples experienced decreasing moisture content and swelling ratios with increasing CP content, producing a more compact and hydrophobic structure. Optical properties, such as color and clarity, were affected by increased CP loadings, with darker films and reduced transparency at these higher CP levels. Thus, it can be stated that CP powder is a viable natural filler to enhance the properties of PVA-based hydrogel films for various biomedical and packing applications. We demonstrate the applicability of CP as a natural filler to facilitate sustainable hydrogel film design for biomedical and packaging applications. The work addresses both performance challenges and environmental concerns.