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Öğe Advancements and future directions in the antibacterial wound dressings - a review(2021) Bal Öztürk, Ayça; Özkahraman, Bengi; Özbaş, Zehra; Yaşayan, Gökçen; Tamahkar, Emel; Alarçin, EmineWound repair is a complex process that has not been entirely understood. It can conclude in several irregularities. Hence, designing an appropriate wound dressing that can accelerate the healing period is critical. Infections, a major obstacle to wound repair, cause an elevated inflammatory responses and result in ultimate outcome of incomplete and prolonged wound repair. To overcome these shortcomings, there is a growing requirement for antibacterial wound dressings. Dressings with antibacterial activities and multifunctional behaviors are highly anticipated to avoid the wound infection for successful healing. The aim of this review is not only to concentrate on the importance of antibacterial dressings for wound healing applications but also to discuss recent studies and some future perspectives about antibacterial wound dressings.Öğe Current strategies and future perspectives of skin-on-a-chip platforms: innovations, technical challenges and commercial outlook(Bentham Science Publ Ltd, 2018) Bal Öztürk, Ayça; Miccoli, Beatrice; Avcı Adalı, Meltem; Mogtader, Ferzaneh; Sharifi, Fatemeh; Cecen, Berivan; Yaşayan, Gökçen; Braeken, Dries; Alarçin, EmineThe skin is the largest and most exposed organ in the human body. Not only it is involved in numerous biological processes essential for life but also it represents a significant endpoint for the application of pharmaceuticals. The area of in vitro skin tissue engineering has been progressing extensively in recent years. Advanced in vitro human skin models strongly impact the discovery of new drugs thanks to the enhanced screening efficiency and reliability. Nowadays, animal models are largely employed at the preclinical stage of new pharmaceutical compounds development for both risk assessment evaluation and pharmacokinetic studies. On the other hand, animal models often insufficiently foresee the human reaction due to the variations in skin immunity and physiology. Skin-on-chips devices offer innovative and state-of-the-art platforms essential to overcome these limitations. In the present review, we focus on the contribution of skin-on-chip platforms in fundamental research and applied medical research. In addition, we also highlighted the technical and practical difficulties that must be overcome to enhance skin-on-chip platforms, e. g. embedding electrical measurements, for improved modeling of human diseases as well as of new drug discovery and development.Öğe Development and characterization of oxaceprol-loaded poly-lactide-co-glycolide nanoparticles for the treatment of osteoarthritis(Wiley, 2020) Alarçin, Emine; Demirbağ, Çağlar; Karslı Ceppioğlu, Seher; Kerinnoğlu, Oya; Bal Öztürk, AyçaOxaceprol is well-defined therapeutic agent as an atypical inhibitor of inflammation in osteoarthritis. In the present study, we aimed to develop and characterize oxaceprol-loaded poly-lactide-co-glycolide (PLGA) nanoparticles for intra-articular administration in osteoarthritis. PLGA nanoparticles were prepared by double-emulsion solvent evaporation method. Meanwhile, a straightforward and generally applicable high performance liquid chromatography method was developed, and validated for the first time for the quantification of oxaceprol. To examine the drug carrying capacity of nanoparticles, varying amount of oxaceprol was entrapped into a constant amount of polymer matrix. Moreover, the efficacy of drug amount on nanoparticle characteristics such as particle size, zeta potential, morphology, drug entrapment, and in vitro drug release was investigated. Nanoparticle sizes were between 229 and 509 nm for different amount of oxaceprol with spherical smooth morphology. Encapsulation efficiency ranged between 39.73 and 63.83% by decreasing oxaceprol amount. The results of Fourier transform infrared and DSC showed absence of interaction between oxaceprol and PLGA. The in vitro drug release from these nanoparticles showed a sustained release of oxaceprol over 30 days. According to cell culture studies, oxaceprol-loaded nanoparticles had no cytotoxicity with high biocompatibility. This study was the first step of developing an intra-articular system in the treatment of osteoarthritis for the controlled release of oxaceprol. Our findings showed that these nanoparticles can be beneficial for an effective treatment of osteoarthritis avoiding side effects associated with oral administration.Öğe Development of mucoadhesive modified kappa-carrageenan/pectin patches for controlled delivery of drug in the buccal cavity(Wiley, 2021) Özkahraman, Bengi; Özbaş, Zehra; Yaşayan, Gökçen; Püren Akgüner, Zeynep; Yarımcan, Filiz; Alarçin, Emine; Bal Öztürk, AyçaIn this study, modified kappa-carrageenan/pectin hydrogel patches were fabricated for treatment of buccal fungal infections. For this purpose, kappa-carrageenan-g-acrylic acid was modified with different thiolated agents (L-cysteine and 3-mercaptopropionic acid), and the thiol content of the resulting modified kappa-carrageenan was confirmed by elemental analyzer. Then, the hydrogel patches were fabricated, and characterized by Fourier-transform infrared spectroscopy, thermogravimetric analysis, ex vivo mucoadhesion test, and swelling behavior. Triamcinolone acetonide was added either directly or by encapsulating within the poly(lactic-co-glycolic acid) nanoparticles. The release amount of the drug from the directly loaded patch was 7.81 mg/g polymer, while it was 3.28 mg/g polymer for the encapsulated patch with the same content at 7 hr. The hydrogel patches had no cytotoxicity by cell culture studies. Finally, the drug loaded hydrogel patches were demonstrated antifungal activity against Aspergillus fumigatus and Aspergillus flavus. These results provide that the novel modified kappa-carrageenan and pectin based buccal delivery system has promising antifungal property, and could have advantages compared to conventional buccal delivery systems.Öğe The effect of thiol functional groups on bovine serum albumin/chitosan buccal mucoadhesive patches(Editions de Sante, 2022) Bal Öztürk, Ayça; Alarçin, Emine; Özbaş, Zehra; Özkahraman, Bengi; Torkay, GülşahIn this research, the effect of thiol functional groups on bovine serum albumin (BSA)/chitosan (Chi) based buccal mucoadhesive patch was investigated. Thiolated BSA (BSA-SH) was prepared via 2-mercaptoethanol. FTIR and 1H NMR results confirmed that BSA-SH was synthesized successfully. The buccal mucoadhesive patches were fabricated by the solvent casting method. Following the structural characterization of BSA/Chi and BSA-SH/Chi buccal patches, the mechanical characterization was performed by tensile tests. The drug release from triam- cinolone acetonide (TR) loaded buccal patches was evaluated in-vitro in simulated salivary. According to the ex- vivo buccal adhesion experiments, the mechanical and mucoadhesion properties of BSA-SH/Chi buccal patch had improved compared to BSA/Chi buccal patch. The total cumulative TR permeated after 12 h was higher for BSA- SH/Chi than BSA/Chi buccal patches. The developed mucoadhesive buccal patches were found to be biocom- patible in vitro. To conclude, the thiolated BSA-SH/Chi buccal adhesive patch is a promising biomaterial for a satisfied drug delivery, which provides advantages for various oral applications.Öğe Gelatin methacryloyl/nanosilicate nanocomposite hydrogels encapsulating dexamethasone with a tunable crosslinking density for bone repair(Editions de Sante, 2022) Alarçin, Emine; Dokgöz, Ayşe Begüm; Akgüner Püren, Zeynep; Seki, Hatice Kübra; Bal Öztürk, AyçaDespite various strategies have been proposed to accelerate bone regeneration, the treatment of bone defects in critical size still remains a clinical challenge. In this study, we fabricated nanocomposite gelatin methacryloyl (GelMA)/nanosilicate (NS) hydrogels for the delivery of dexamethasone (DEX), and systematically investigated their performance in drug delivery for bone repair. Nanocomposite hydrogels were fabricated by mold casting, and exposed to ultraviolet (UV) light to induce covalent crosslinking. Afterwards, we conducted a systematic characterization study to determine the effects of varying NS concentration, GelMA methacrylation degree and UV exposure time on mechanical, structural, and drug release behaviors of nanocomposite hydrogels. In particular, the higher methacrylation degree of GelMA, longer UV exposure and the presence of NS exhibited gradually enhanced mechanical properties. For instance, the compressive strengths of nanocomposite hydrogels containing 0% (w/v) NS (G0NS120) and 3% (w/v) NS (G3NS120) at 120 s of UV exposure were 194.816 kPa–367.284 kPa (p < 0.001), respectively. Similarly, they exhibited higher swelling ratio (%) and slower degradation rate (%) with longer UV exposure and increased NS amount. Nanocomposite hydrogels revealed slower drug release rate due to longer UV exposure and increased NS amount. At day 14 of the release study, 99.53% and 60.687% of DEX were released from G0NS120 and G3NS120, respectively. Particularly, the nanocomposite GelMA/ NS hydrogels supported osteoblast adhesion well, and NS and DEX exhibited synergistic effect on osteoblast proliferation with 5.01 fold increase after 7 days of culture. Our results clearly showed that GelMA/NS nanocomposite hydrogels with tunable physiochemical and drug carrier properties could provide a favorable option for accelerating bone repair.Öğe Natural polymers for wound dressing applications(Elsevier, 2022) Yaşayan, Gökçen; Alarçin, Emine; Bal Öztürk, Ayça; Avcı Adalı, MeltemWound care is a hot topic in recent years. Recent wound treatment regimens use dressings fabricated from natural materials due to their significant advantages compared to traditional or synthetic dressings. Because of their importance, in this chapter, wound dressings are discussed with an emphasis on the use of natural polymers and their function in the healing process. After a brief introduction to wounds and classification of wound dressings, the chapter focuses on (i) the impact of natural materials on wound dressing design such as mechanical properties, texture, wettability, composition, and porosity; (ii) commonly used natural polymers and their combinations with synthetic polymers and other bioactive components; (iii) state-of-the-art fabrication methods of dressings; and finally, (iv) other nature-derived materials as wound dressings such as decellularized skin extracellular matrix and tissue-engineered skin substitutes. © 2022 Elsevier B.V.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 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 Selection of natural biomaterials for micro-tissue and organ-on-chip models(2022) Bal Öztürk, Ayça; Cecen, Berivan; Yaşayan, Gökçen; Alarçin, Emine; Koçak, Polen; Tutar, Rümeysa; Kozacı, Leyla Didem; Ryon Shin, Su; K Miri, AmirThe desired organ in micro-tissue models of organ-on-a-chip (OoC) devices dictates the optimum biomaterials, divided into natural and synthetic biomaterials. They can resemble biological tissues' biological functions and architectures by constructing bioactivity of macromolecules, cells, nanoparticles, and other biological agents. The inclusion of such components in OoCs allows them having biological processes, such as basic biorecognition, enzymatic cleavage, and regulated drug release. In this report, we review natural-based biomaterials that are used in OoCs and their main characteristics. We address the preparation, modification, and characterization methods of natural-based biomaterials and summarize recent reports on their applications in the design and fabrication of micro-tissue models. This article will help bioengineers select the proper biomaterials based on developing new technÖğe Tissue adhesives: From research to clinical translation(Elsevier B.V., 2021) Bal Öztürk, Ayça; Cecen, Berivan; Avcı Adalı, Meltem; Topkaya, Seda Nur; Alarçin, Emine; Yaşayan, Gökçen; Li, Yi Chen Ethan; Bulkurcuoğlu, Bünyamin; Akpek, Ali; Avcı, Hüseyin; Shi, Kun; Shin, Suryon; Hassan, ShabirSutures, staples, clips, and skin closure strips are used as the gold standard to close wounds after an injury. In spite of being the present standard of care, the utilization of these conventional methods is precarious amid complicated and sensitive surgeries such as vascular anastomosis, ocular surgeries, nerve repair, or due to the high-risk components included. Tissue adhesives function as an interface to connect the surfaces of wound edges and prevent them from separation. They are fluid or semi-fluid mixtures that can be easily used to seal any wound of any morphology-uniform or irregular. As such, they provide alternatives to new and novel platforms for wound closure methods. In this review, we offer a background on the improvement of distinctive tissue adhesives focusing on the chemistry of some of these products that have been a commercial success from the clinical application perspective. This review is aimed to provide a guide toward the innovation of tissue bioadhesive materials and their associated biomedical applications.