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Öğe Bactericidal and in vitro osteogenic activity of nano sized cobalt-doped silicate hydroxyapatite(Elsevier Sci Ltd, 2022) Alshemary, Ammar Z.; Hussain, Rafaqat; Dalgic, Ali Deniz; Evis, ZaferHydroxyapatite (HA) particles with enhanced antibacterial properties can be prepared by integrating metal ions into the crystal structure of the nanoparticles. Cobalt and silicate ions containing HA (Co/Si-HA) with the formula Ca10-xCox(PO4)(6-y)(SiO4)(y)(OH)(2) (x = 0.2, 0.6, and 1.0 and y = 0.5) was successfully synthesised by using microwave-assisted wet precipitation method. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and inductively coupled plasma mass spectrometry (ICP-MS) techniques were used to characterise the synthesised nanoparticles. The results revealed that the incorporation of SiO44- ions increased the lattice parameters and decreased the crystallite size of HA. However, the incorporation of Co(2+)ions led to the reduction of lattice parameters and the particle size of the SiHA nanoparticles. In vitro antibacterial activity of materials was evaluated using disk diffusion and minimum inhibitory concentration (MIC) protocols. The findings indicated that incorporating Co2+ ions into SiHA inhibited the growth of Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). The cytotoxicity of materials evaluated using the Sarcoma osteogenic (Saos-2) cell line revealed that they were cytocompatible and exhibited no adverse side effects. The osteogenic differentiation of cells was confirmed by the significant increase in the alkaline phosphatase (ALP) activity by incorporating Co2+/SiO44- ions into the HA crystal structure. Our results show that the nanoparticles prepared in this study have a promising future in biomaterial-tissue engineering applications.Öğe Collagen-carrageenan-chitosan sponge reinforced with 3D-printed polycaprolactone mesh for skin tissue engineering(Wiley, 2026) Yesiloglu, Buket; Barer, Neslihan; Baran, Eray A.; Serin, Erdal; Dalgic, Ali Deniz; Erdemli, Bengi Yilmaz; Tahmasebifar, AydinBiopolymers have gained prominence due to their potential in tissue engineering, which includes hydrophilicity, lower toxicity, reduced immune rejection, biocompatibility and biodegradability. However, biopolymers typically exhibit low mechanical strength, which decreases their application potential in tissue engineering. Composites of natural and synthetic polymers offer a robust solution to overcome this challenge, as the stiffness and durability of composites are enhanced by the presence of synthetic polymers. This study investigates two composite sandwich model scaffolds for skin tissue engineering, focusing on their structural and regenerative properties. The composite scaffolds were fabricated by combining freeze-drying and 3D-printing techniques. The outer layers of the scaffolds were fabricated using collagen-carrageenan (CO/CA-PCL) or collagen-carrageenan-chitosan (CO/CA/CH-PCL) through freeze drying, whereas the core layer was formed by 3D-printed polycaprolactone (PCL) mesh. Crosslinking was achieved in the vapor phase of glutaraldehyde and scaffold groups preserved their structure through 28 days after an initial weight loss on day 1. The CO/CA/CH-PCL scaffold showed a lower degradation rate with a cumulative weight loss of 28.6 +/- 5.5% compared to the CO/CA-PCL scaffold which indicates improved stability of the three-polymer sponge. Both scaffolds achieved water retention above 800% after 14 days of incubation which is critical for wound healing. Tensile strength of both scaffolds was successfully supported by 3D-printed PCL mesh. In vitro study has shown that the chitosan-bearing CO/CA/CH-PCL scaffold is promising for use in skin tissue engineering by supporting L929 attachment and high L929 cell viability. (c) 2025 Society of Chemical Industry.Öğe Development of PCL/PVA/PCL scaffold for local delivery of calcium fructoborate for bone tissue engineering(Turkish Energy, Nuclear and Mining Research Agency, 2024) Dalgic, Ali DenizCalcium fructoborate (CaFB) has gathered attention due to its boron and calcium content, both of which are known to support bone health, deposition and regeneration. Previous studies have shown that CaFB has a positive effect on bone health and has been proven to promote bone-like properties. In light of this information, a local CaFB delivering scaffold could improve bone regeneration in cases of bone tissue loss. This study aimed to design a layer-by-layer polymeric sponge capable of achieving controlled local delivery of CaFB to improve bone tissue healing. The dose-dependent effect of CaFB on the cell viability of the Saos-2 cell line was investigated in vitro. Layer-by-layer structure of the polymeric scaffold supported controlled release of CaFB, with 33.9±7.4% released after 7 days of incubation. CaFB at 31.25 µg/mL concentration was able to improve Saos-2 cell viability up to 174.7±24.1% and 127.7±8.7% after 1 and 4 days of incubation. After 7 days of incubation CaFB treatment at concentrations of 250, 125, 62.5 and 31.25 µg/mL improved cell viability up to 194.3±47.7, 155.3±17.7, 149.4±5.4 and 132.5±13.3%. The polycaprolactone/polyvinyl alcohol/polycaprolactone (PCL/PVA/PCL) scaffold supported the viability of cells for 7 days and was shown to be biocompatible. The results of this study showed that CaFB is a potential compound that can be locally delivered within a scaffold system to improve bone tissue regeneration. © 2024, Turkish Energy, Nuclear and Mining Research Agency. All rights reserved.Öğe Diatom silica frustules-doped fibers for controlled release of melatonin for bone regeneration(Pergamon-Elsevier Science Ltd, 2023) Dalgic, Ali Deniz; Atila, Deniz; Tezcaner, Aysen; Gurses, Senih; Keskin, DilekSustained release of a bioactive agent from a tissue engineering scaffold is one of the most common strategies to improve regenerative potential of the construct. However, depending on the chemistry of the agent, achieving high enough loading and controlled release can be challenging depending on the scaffold materials. These shortcomings can be solved by novel scaffold design fabricated by appropriate techniques and materials for the target tissue. In this study, an electrospun scaffold was designed to improve osteogenic activity of cells and diatom silica frustules were used to sustain loading and controlled release of a hydrophilic molecule, melatonin. Fibrous scaffolds were produced via wet electrospinning of the polymer blend solution poly(hydroxybutyrate-co- hydroxyvalerate (PHBV)/poly(epsilon-caprolactone) (PCL) which contains melatonin loaded diatom frustules. In the 3D fiber matrix diatom frustules were covered with a polymer coat which successfully lowered melatonin release more than half through 7 days achieving a controlled release. Melatonin had a concentration dependent effect on ALP activity of cells, while scaffolds bearing melatonin loaded frustules have significantly improved ALP activity of Saos-2 cells. Developed scaffold system has successfully induced osteogenic activity by controlled melatonin delivery and silica nature of diatom frustules which hold potential use for bone tissue engineering.Öğe Graphene oxide reinforced doped dicalcium phosphate bone cements for bone tissue regenerations(Springer, 2022) Motameni, Ali; Alshemary, Ammar Z.; Dalgic, Ali Deniz; Keskin, Dilek; Evis, ZaferArtificial bone cements have widespread applications in orthopedic and dental surgeries. Nevertheless, there is a need to develop novel materials for artificial bone cements due to limitations like short-service life, weak interaction and attachment with living hard tissue, and the inability to facilitate bone regeneration of calcified tissues rather than replacing them. In the present research, a novel combination of lanthanum (La3+) ions doped dicalcium phosphate (DCP) (La-DCP) and 1.5-3.5 wt.% of graphene oxide (GO) doped La-DCP bone cement materials were successfully synthesized and reported for the first time. Acid/base interaction between La-beta-tricalcium phosphate (La-beta TCP) and monocalcium phosphate monohydrate (MCPM) in the presence of water was the basis for making the La-DCP cements. The synthesized cements were characterized using the XRD, FTIR, FESEM, UV-Vis and TGA techniques. Produced material had La-DCP as in the monetite phase, and La-DCP particles were formed in agglomerates of irregular shapes. The presence of GO enhanced the growth rate of monetite particles, significantly decreased the setting time of the La-DCP bone cement, enhanced mechanical properties and enhanced the adsorption capacity of La-DCP. In vitro studies showed that synthesized GO/La-DCP bone cements were biocompatible, and the proliferation and differentiation properties of human osteosarcoma (Saos-2) cells were significantly improved with the addition of GO. In summary, the synthesized GO/La-DCP bone cement materials, which exhibit good biocompatibility and mechanical properties, have the potential to be employed in bone defect healing.Öğe Injectable Liposome-Loaded Hydrogel Formulations with Controlled Release of Curcumin and ?-Tocopherol for Dental Tissue Engineering(Wiley, 2024) Atila, Deniz; Dalgic, Ali Deniz; Krzeminska, Agnieszka; Pietrasik, Joanna; Gendaszewska-Darmach, Edyta; Bociaga, Dorota; Kumaravel, VigneshAn injectable hydrogel formulation is developed utilizing low- and high-molecular-weight chitosan (LCH and HCH) incorporated with curcumin and alpha-tocopherol-loaded liposomes (Lip/Cur+Toc). Cur and Toc releases are delayed within the hydrogels. The injectability of hydrogels is proved via rheological analyses. In vitro studies are conducted using human dental pulp stem cells (hDPSCs) and human gingival fibroblasts (hGFs) to examine the biological performance of the hydrogels toward endodontics and periodontics, respectively. The viability of hDPSCs treated with the hydrogels with Lip/Cur+Toc is the highest till day 14, compared to the neat hydrogels. During odontogenic differentiation tests, alkaline phosphatase (ALP) enzyme activity of hDPSCs is induced in the Cur-containing groups. Biomineralization is enhanced mostly with Lip/Cur+Toc incorporation. The viability of hGFs is the highest in HCH combined with Lip/Cur+Toc while wound healing occurs almost 100% in both (Lip/Cur+Toc@LCH and Lip/Cur+Toc@HCH) after 2 days. Antioxidant activity of Lip/Cur+Toc@LCH on hGFs is significantly the highest among the groups. Antimicrobial tests demonstrate that Lip/Cur+Toc@LCH is more effective against Escherichia coli whereas so is Lip/Cur+Toc@HCH against Staphylococcus aureus. The antimicrobial mechanism of the hydrogels is investigated for the first time through various computational models. LCH and HCH loaded with Lip/Cur+Toc are promising candidates with multi-functional features for endodontics and periodontics.Öğe Investigation of the effect of ghrelin on bone fracture healing in rats(Wiley, 2021) Erener, Tamer; Ceritoglu, Kubilay Ugurcan; Aktekin, Cem Nuri; Dalgic, Ali Deniz; Keskin, Dilek; Geneci, Ferhat; Ocak, MertGhrelin is known to have effects on proliferation and differentiation of osteoblasts and improvement of bone mineral density in rats. However, no experimental research on ghrelin's effects on fracture healing has been reported. In this context, the effect of ghrelin on the union of femoral shaft fractures was examined in this study by evaluating whether ghrelin will directly contribute to fracture healing. Forty male Wistar-Albino rats were divided into two groups as control and experimental (ghrelin treated) and standard closed shaft fractures were created in the left femurs of all rats. Daily ghrelin injections were applied to the experimental groups and equal numbers of rats were killed after 14 and 28 days following fracture formation. Tissue samples were examined with radiological, biomechanical, biochemical and histological analyses. Densitometry study showed that bone mineral density was improved after 28 days of ghrelin treatment compared to control. On histological examination, at the end of the 14 and 28 days of recovery, significant union was observed in the ghrelin-treated group. The ghrelin-treated group had higher breaking strength and stiffness at the end of 28 days of recovery. Biochemically, ALP levels were found to be higher in the ghrelin-treated group at the end of 28 days of recovery. Results showed that ghrelin directly contributes to fracture healing and it is promising to consider the effect of ghrelin on fracture healing in human studies with pharmacological applications.Öğe Mechanical and biological evaluation of ?-dicalcium silicate/dicalcium phosphate-based cements: promising materials for biomedical applications(Taylor & Francis Ltd, 2025) Alshemary, Ammar Z.; Marandi, Almataz Bellah; Ali, Daver; Kose, Tugba; Dalgic, Ali Deniz; Motameni, Ali; Evis, ZaferThis study explores the synthesis and evaluation of beta-Dicalcium silicate and Dicalcium phosphate-based cements for biomedical use. beta-Tricalcium phosphate was synthesized using microwave-assisted wet precipitation, while beta-Dicalcium silicate was prepared via the sol-gel method. Composites with varying beta-Dicalcium silicate contents (20%, 30%, 40%) were formulated and characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, and Field emission scanning electron microscope analyses. The 40% beta-Dicalcium silicate composite showed the highest compressive strength at 10.22 MPa. Antibacterial tests against Staphylococcus aureus revealed that gentamicin-loaded Dicalcium phosphate cement had superior properties. Cytotoxicity studies using the Osteogenic sarcoma cell line revealed that the beta-Dicalcium Silicate /Dicalcium Phosphate composites supported better cell viability compared to pure Dicalcium phosphate cement, with the 20% beta-Dicalcium silicate /Dicalcium phosphate composition being the most effective in promoting cell growth. These findings suggest that beta-Dicalcium silicate /Dicalcium phosphate composites hold promise for biomedical applications.Öğe Natural origin bilayer pullulan-PHBV scaffold for wound healing applications(Elsevier, 2022) Dalgic, Ali Deniz; Koman, Ezgi; Karatas, Ayten; Tezcaner, Aysen; Keskin, DilekSkin tissue loss that occurs by injury and diseases can turn into chronic wounds as a result of complications alongside infection. Chronic wounds fail to heal by themselves and need advanced treatments like engineered wound dressings and regenerative scaffolds. In this study, a novel, natural origin, bilayer electrospun scaffold was produced from pullulan (PUL) and poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) biopolymers. PHBV production by Cupriavidus necator bacterial strain was optimized and produced polymer was characterized. Characteristic peaks and bands of PHBV were observed by H-NMR and FTIR analyses. Valerate mol percent of produced PHBV copolymer was determined by H-NMR. Average molecular weight of the polymer was determined by SLS technique and crystallinity of PHBV was calculated from DSC curve. Bilayer scaffold was produced by electrospinning of hydrophilic PUL fibrous membrane onto wet-electrospun hydrophobic PHBV 3D fibrous mat. Bilayer scaffold was designed to involve regenerative and barrier fibrous layers. Nano fibrous PUL membrane with smaller pore size was efficient as a barrier against bacterial transmission while enabling optimum oxygen and water vapor transmission. Water retention and degradation properties were found to be optimum for a skin tissue scaffold. In vitro studies showed that PUL membrane sustained L929 cell proliferation while preventing cells from migrating inside the barrier phase while PHBV layer supported cell viability, proliferation, and migration, creating a regenerative 3D structure. Results showed that, novel natural origin PUL/PHBV bilayer scaffold is a promising candidate for wound healing applications.Öğe Using embossing ice particulate method to prepare polyvinyl alcohol/ pullulan hydrogels with surface open pores loaded with microspheres for breast cancer treatment(Elsevier, 2024) Barer, Neslihan; Tunc, Bugse; Yilmaz, Bengi; Ng, Yuk Yin; Dalgic, Ali DenizIn the post -operative treatment of breast cancer, early prevention of locoregional recurrence is crucial to avoid metastasis of cells from leftover microtumor tissues. The limitations in conventional drug delivery systems show a growing clinical demand for disease -specific drug -releasing systems. This study explores a novel poly(vinyl alcohol)/pullulan (PVA/PUL) hydrogel system for local drug delivery in post -operative breast cancer treatment. Hydrogel was produced by combination of lyophilization and embossing ice particulate techniques to create microspheres loaded open pores on the hydrogel surface for localized release of doxorubicin-loaded polycaprolactone microspheres (DOX-PCL-MSs). PVA/PUL hydrogel was successfully crosslinked with glutaraldehyde and stabilized hydrogel structure has possessed slow degradation rate and increasing water retention through 12 days. Release of DOX after 7 and 16 days from DOX-PCL-MSs loaded hydrogels were slower with a 6.2 +/- 8.9 % and 56.6 +/- 4.5 % release compared to 60.9 +/- 14.6 % and 76.8 +/- 19.7 % release from free DOX loaded hydrogel since DOX release was controlled by PCL microspheres. When interacted with human breast cancer cell line (MCF-7), DOX-PCL-MSs were able to disrupt cell and spheroid morphology after 7 days at concentrations as low as 12 mu g/mL loaded DOX. In vitro cytotoxicity study has showed that, DOX-PCL-MSs loaded hydrogel was able to decrease MCF-7 viability after 7 days of incubation with controlled release of DOX. While free DOX releasing hydrogel has lost cytotoxic activity even after 4 days of incubation. Furthermore, ability of PVA/PUL hydrogel to support L929 cell attachment was shown in the study, suggesting hydrogels potential for promoting tissue regeneration after anti -cancer treatment. The study reveals that PVA/PUL hybrid hydrogels loaded with DOXPCL-MSs has impactful potential in post -surgical treatment of breast cancer.
