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Öğe Aloe vera-based antibacterial porous sponges for wound dressing applications(SPRINGER, 2021) Tamahkar, Emel; Özkahraman, Bengi; Özbaş, Zehra; İzbudak, Burçin; Yarımcan, Filiz; Boran, Filiz; Bal Öztürk, AyçaThe antibacterial sponges with high macroporosity, high interconnectivity and high biocompatibility is a significant concern for wound healing applications. In this work, novel Aloe vera (AV) based sponges were developed via subsequent lyophilization with further chemical crosslinking throughout the double network sponges. Single network was composed of gelatin-sodium alginate (G-SA) while the double network using gelatin-sodium alginate- sodium hyaluronate (G-SA-HA) was produced with the addition of hyaluronic acid solution into the gelatin-sodium alginate matrix. Lastly, Aloe vera as the bioactive agent was fabricated throughout the gelatin-sodium alginate-sodium hyaluronate matrix. The AV-based sponges demonstrated large pores with high interconnectivity. The swelling degree of the AV-based sponges were higher than that of G-SA and G-SA-HA sponges. The release of AV from the sponges reached an equilibrium value after 24 h showing a more controlled release at pH 5.5 than at pH 7.4. AV-based sponges showed antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae and Bacillus cereus and displayed any cytotoxicity against Mesenchymal stem cells.Öğe Assessment of Centella Asiatica Extract Containing Dual-crosslinked Gel-MA/Pec Hydrogels as Wound Dressing(2022) Aklar, Demet Akalgan; Albayrak, Betül; Gelal, Melisa; İzbudak, Burçin; Özkahraman, Bengi; Öztürk, Ayça BalIn the present work, 3D-printed wound dressings containing different amounts of Centella Asiatica (CA) extract were synthesized via dual-crosslinking method. Methacrylic anhydride modified gelatin (Gel-MA) and pectin (Pec) were chosen as the base material for dressings. A dual crosslinked network was formed with Gel-MA photo-crosslinking using Irgacure 2959 and Pectin (Pec) psychical-crosslinking using Ca++ ions. Meanwhile, the developed dual-crosslinked hydrogel dressings were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and mechanical, swelling, in vitro degradation as well as ex vivo bioadhesion tests. As the amount of CA in the dressing hydrogels increased, the degradation rates increased. In addition, the prepared dressings provide good bioadhesion on the chicken skin. Moreover, (3-(4,5-Dimethylthiazol- 2-yl)-2,5-Diphenyltetrazolium Bromide) (MTT) assay revealed cell viability of Gel-MA/ Pec hydrogel dressings containing CA extract. The results presented the dressings as a promising biomaterial to be used for wound healing purposes, which should be further investigated in future.Öğe Boric acid-impregnated silk fibroin/gelatin/hyaluronic acid-based films for improving the wound healing process(Journal of Applied Polymer Science, 2021) Özen, Nurten; Özbaş, Zehra; İzbudak, Burçin; Emik, Serkan; Özkahraman, Bengi; Bal Öztürk, AyçaRecently, with the progression in wound dressings, the importance of the biocompatible material with enhanced features for potential applications in the biomedical field has been more developed. Current strategies focus on the acceleration of the wound healing by systematically designed dressing materials. In this study, biocompatible hydrogel films with the combination of silk fibroin, hyaluronic acid and gelatin biopolymers were fabricated. To gain the enhanced wound healing behavior of wound dressings, boric acid (BA) was formulated in various ratios. The prepared hydrogel films were characterized in terms of FTIR, TGA, DSC, and SEM analysis. Following to the swelling and mechanical tests, in vitro biocompatibility and wound healing tests were performed against L929 fibroblast cell line. Results suggest that the presence of 1% (wt/vol) BA in the formulation of silk fibroin/gelatin/hyaluronic acid based hydrogel films is the key in providing such an enhanced mechanical and wound healing feature and may offer an alternative approach for wound healing treatment. © 2021 Wiley Periodicals LLC.Öğe The effect of LDHs nanoparticles on the cellular behavior of stem cell-laden 3D-bioprinted scaffold(SAGE PUBLICATIONS, 2022) İzbudak, Burçin; Bal Öztürk, AyçaThree-dimensional (3D)-bioprinting as an emerging approach for tissue engineering possesses the promise to create highly mimicked organs or tissues by using computer-aided design. For biomedical applications in tissue engineering in our previous work, we developed an optimized nanocomposite bioink based on methylacrylated gelatin (GeIMA), methylacrylated chitosan (ChitMA), and double-layered hydroxide (LDHs) nanoparticles by using 3D-bioprinting technology. Herein, we used the previous formulation to fabricate human bone marrow mesenchymal stem cells (hBMMSCs)-laden nanocomposite bioinks. The effect of LDHs nanoparticles on the cellular behaviors of the encapsulated-hBMMSCs in the scaffolds was evaluated for the first time. Live/Dead, PrestoBlue, and DAPI/Actin analysis were carried out to assess the cell viability, proliferation rate, and cellular morphology of encapsulated hBMMSCs within the scaffolds. In addition, osteogenic differentiation studies were performed culturing the scaffolds for up to 21 days. Results show that LDHs nanoparticles in the GeIMA/ChitMA scaffold formulation increased the viability of hBMMSCs, did not cause any adverse effect on the proliferation rate, cell morphology of the hBMMSCs, and increased the Runx2 protein expression of the encapsulated-hBMMSCs in the scaffolds. This study progresses the LDHs containing nanocomposite bioink for cell printing applications in tissue engineering.Öğe Layered double hydroxide-based nanocomposite scaffolds in tissue engineering applications(Royal Society of Chemistry, 2021) İzbudak, Burçin; Çeçen, Berivan; Anaya, Ingrid; Kamal Miri, Amir; Bal Öztürk, Ayça; Karaöz, ErdalLayered double hydroxides (LDHs), when incorporated into biomaterials, provide a tunable composition, controllable particle size, anion exchange capacity, pH-sensitive solubility, high-drug loading efficiency, efficient gene and drug delivery, controlled release and effective intracellular uptake, natural biodegradability in an acidic medium, and negligible toxicity. In this review, we study potential applications of LDH-based nanocomposite scaffolds for tissue engineering. We address how LDHs provide new solutions for nanostructure stability and enhancein vivostudies' success. © The Royal Society of Chemistry 2021.Öğe Optimization of methacrylated gelatin /layered double hydroxides nanocomposite cell-laden hydrogel bioinks with high printability for 3D extrusion bioprinting(John Wiley and Sons Inc, 2022) Alarçin, Emine; İzbudak, Burçin; Yüce Erarslan, Elif; Domingo, Sherif; Tutar, Rümeysa; Titi, Kariman; Kocaağa, Banu; Güner, F. Seniha; Bal Öztürk, AyçaLayered double hydroxides (LDHs) offer unique source of inspiration for design of bone mimetic biomaterials due to their superior mechanical properties, drug delivery capability and regulation cellular behaviors, particularly by divalent metal cations in their structure. Three-dimensional (3D) bioprinting of LDHs holds great promise as a novel strategy thanks to highly tunable physiochemical properties and shear-thinning ability of LDHs, which allow shape fidelity after deposition. Herein, we introduce a straightforward strategy for extrusion bioprinting of cell laden nanocomposite hydrogel bioink of gelatin methacryloyl (GelMA) biopolymer and LDHs nanoparticles. First, we synthesized LDHs by co-precipitation process and systematically examined the effect of LDHs addition on printing parameters such as printing pressure, extrusion rate, printing speed, and finally bioink printability in creating grid-like constructs. The developed hydrogel bioinks provided precise control over extrudability, extrusion uniformity, and structural integrity after deposition. Based on the printability and rheological analysis, the printability could be altered by controlling the concentration of LDHs, and printability was found to be ideal with the addition of 3 wt % LDHs. The addition of LDHs resulted in remarkably enhanced compressive strength from 652 kPa (G-LDH0) to 1168 kPa (G-LDH3). It was shown that the printed nanocomposite hydrogel scaffolds were able to support encapsulated osteoblast survival, spreading, and proliferation in the absence of any osteoinductive factors taking advantage of LDHs. In addition, cells encapsulated in G-LDH3 had a larger cell spreading area and higher cell aspect ratio than those encapsulated in G-LDH0. Altogether, the results demonstrated that the developed GelMA/LDHs nanocomposite hydrogel bioink revealed a high potential for extrusion bioprinting with high structural fidelity to fabricate implantable 3D hydrogel constructs for repair of bone defects.Öğe Osteokondral hasarların onarımına yönelik 3B-biyoyazıcı ile çift-tabakalı nanohibrit doku iskelelerinin geliştirilmesi(İstinye Üniversitesi / Sağlık Bilimleri Enstitüsü, 2021) İzbudak, Burçin; Bal Öztürk, AyçaTez çalışması kapsamında osteokondral defektlerin onarımında kullanılmak üzere 3Bbiyoyazıcı teknolojisi ile kök hücre yüklü jelatin metakrilat/ kitosan metakrilat (GelMA/ChitMA) polimerleri ve LDH nanopartiküleri içeren nanohibrit çift-tabakalı 3B doku iskeleleri geliştirilmiştir. Çift tabakalı doku iskelelerinin alt tabaka kemik dokuyu üst tabaka ise kıkırdak dokuyu taklit edecek şekilde tasarlanmıştır. LDH nanopartiküllerine TGF-ß1 ve rhBMP-2 sinyal molekülleri ayrı ayrı yüklenmiş ve enzim-bağlı immünosorbent testi (ELISA) ile in vitro salım davranışları incelenmiştir. Çift tabakalı doku iskelelerinde enkapsüle edilen kemik iliği mezenkimal kök hücrelerin canlılığı, morfolojisi, gelişimi, proliferasyonu, osteojenik ve kondrojenik farklılaşma özellikleri incelenmiştir. Geliştirilen kemik doku iskelelerinde osteojenik farklılaştırma kapasiteleri Hematoksilen&Eosin, Alizarin Red S, Von Kossa ve immünfloresan boyamaları ile değerlendirilmiştir. Geliştirilen kıkırdak doku iskelelerinde kondrojenik farklılaştırma kapasiteleri Hematoksilen&Eosin, Alcian Blue, Toluidin mavisi, GAG anlizi ve immünfloresan boyamaları ile değerlendirilmiştir. Tüm sonuçlar LDH nanopartikül katkılı çift fazlı GelMA/ChitMA nanohibrit doku iskelelerinin osteokondral defektlerin onarımı için kullanılabileceğini göstermiştir.Öğe Photo-crosslinkable chitosan and gelatin-based nanohybrid bioinks for extrusion-based 3D-bioprinting(TAYLOR & FRANCIS AS, 2021) Yüce Erarslan, Elif; Tutar, Rümeysa; İzbudak, Burçin; Alarçin, Emine; Kocaağa, Banu; Güner, F. Seniha; Emik, Serkan; Bal Öztürk, AyçaIn the last decade, 3D-bioprinting has attracted attention due to its capability to produce complex scaffolds. The selection of suitable biomaterials for the bioink design is very important for the success of 3D-bioprinting. In this study, chitosan and gelatin were chemically modified into methacrylated chitosan (ChiMA) and methacrylated gelatin (GelMA) with the methacrylic anhydride in order to obtain crosslinking points on the polymeric backbone. The eligible bioinks were formulated with the layered double hydroxide nanoparticles (LDHs). The effect of changing the amount of LDHs on the printability of the bioinks was evaluated by using rheological analysis and printability test with the extrusion-based 3D-bioprinting. The bioinks were crosslinked under UV light. Mechanical, swelling, degradation properties, and cell-adhesion behaviors of the obtained ChiMA/GelMA nanohybrid scaffolds containing LDHs were investigated. Based on the rheology and the printing results, ChiMA/GelMA nanohybrid scaffold containing 5% LDHs (ChiMA-G5) was found to be the optimal bioink. Notably, compression strength, elongation at break, and elastic modulus of ChiMA-G5 scaffold were higher than neat and other ChiMA/GelMA scaffolds. In vitro cell culture studies showed that LDHs do not have any negative effects. These findings indicate that the developed ChiMA-G5 bioink has great potential as a bioink to utilize for tissue engineering applications.Öğe Photocurable silk fibroin-based tissue sealants with enhanced adhesive properties for the treatment of corneal perforations(2022) Tutar, Rümeysa; Yüce Erarslan, Elif; İzbudak, Burçin; Bal Öztürk, AyçaCorneal defects are associated with corneal tissue engineering in terms of vision loss. The treatment of corneal defects is an important clinical challenge due to a uniform corneal thickness and the apparent lack of regenerative ability. In this work, we synthesized a biocompatible and photocrosslinkable ocular tissue adhesive composite hydrogel prepared by using methacrylated gelatin (GelMA), which is called the most favorable derivative of gelatin used as a tissue adhesive, silk fibroin (SF), and GelMA/SF (GS) with high adhesion behaviours for use in corneal injuries. The adhesion behaviours of the materials prepared in the presence of silk fibroin were improved. Importantly, the effect of different UV curing times on the adhesion properties of the prepared materials was also investigated. The prepared GS tissue adhesives showed high physiological adhesion. GS can be modulated to increase its adhesive strength up to 3 times compared to G. GS was also found to be biocompatible and have a high healing potential. In addition, the obtained transmission value of GS is also close to that of the human cornea. GS supported cellular adhesion and proliferation. The burst pressure strength for fresh cornea of the GS-60s sealants (144.5 ± 13 kPa) was determined to be higher than that of the G-60s sealants (52.6 ± 33.5 kPa).Öğe Preparation of tetracycline hydrochloride loaded chitosan/silk fibroin/ZnO antibacterial biocomposite hydrogel sponges for wound healing application(Springer, 2023) Giray, Betül; Kaptan, Yasemin; Karal Yılmaz, Okşan; İzbudak, Burçin; Yılmaz, Bengi; Bal Öztürk, AyçaThree-dimensional (3D) porous biocomposite hydrogel sponges consisting of chitosan (CS), silk fibroin (SF) and ZnO nanoparticles (ZnO NPs) were prepared by the freeze-drying method. The biocomposite was also loaded with tetracycline hydrochloride (TCH) and its wound healing efficacy was investigated in an attempt to enhance healing through the release of the drug. The chemical nature, composition, thermal properties and morphology of the sponges were revealed by FTIR, TGA, and SEM/EDX, analysis. The hydrogels presented the swelling degree in the range of 650-1180% at pH 7.4; 1300-3160% at pH 5.5 and 550-920% at pH 9.0, respectively. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay demonstrated the cytocompatibility of CS/SF/ZnO hydrogels against Wharton's jelly mesenchymal stem cells (WJ-MSCs). CS/SF/ZnO-0 and CS/SF/ZnO-0.5 hydrogels exhibited no cytotoxic effect. In addition, CS/SF/ZnO hydrogels exhibited antimicrobial activity against some tested gram-positive and gram-negative bacteria. Physical immobilization of TCH in hydrogel matrix resulted in sustained release of the drug for more than 2 days at pH 7.4. The results showed that CS/SF/ ZnO-0.5 hydrogel sponge is safe, convenient and could be effective for wound healing applications.Öğe Synthesis, characterization, in vitro cytotoxicity of novel metallo phthalocyanines with four methylpropiophenonyl clusters and their effects on caenorhabditis elegans thermotolerance(SPRINGER INT PUBL AG, 2022) Şenoğlu, Sema; Güleç, Meltem; Yavuz Dokgöz, Elif; Bal Öztürk, Ayça; İzbudak, Burçin; Salih, Bekir; Olgun, Abdullah; Ceyhan, TanjuPhthalocyanines (Pcs) have the potential to be used in many medical applications. Novel Zn (II), Co (II), and Cu (II) phthalocyanines (Pcs) 4, 5, and 6, respectively, containing four methylpropiophenonyl units at the peripheral positions were described. Pcs were synthesized by cyclotetramerization of the previously prepared precursor 2-hydroxy-4'-[2-(3,4-dicyanophenoxyethoxy)]-2-methylpropiophenone 3 with the presence of metal salts under nitrogen atmosphere. The compounds were characterized by elemental analysis, IR (Infrared spectroscopy), UV-visible spectroscopy, and Laser Desorption ionization time-of-flight mass spectroscopy (LDI-TOF-MS) methods. The compounds were tested for in vitro cytotoxicity in cultured human cells, and thermotolerance in Caenorhabditis elegans (C. elegans). Standard MTT assays were carried out for cytotoxicity testing using HeLa and L929 cells. Results showed that there was no significant decrease in the cell viability with zinc (II), cobalt (II), and copper (II) phthalocyanines (ZnPc, CoPc, and CuPc) at 0.25 mu M concentration. C. elegans survival assay with ZnPc, CoPc, and CuPc under heat stress showed that although a dose-dependent statistically significant toxicity was observed for ZnPc and CuPc, CoPc was not toxic at all concentrations tested and even increased the survival of worms at the 0.050-0.250 mu M concentration range. Therefore, CoPc can be a lead compound for further preclinical studies for its potential in photodynamic therapy (PDT) and anti-aging purposes.
