Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Article Citation - WoS: 14Citation - Scopus: 163D Bioprinting of mouse pre-osteoblasts and human MSCs using bioinks consisting of gelatin and decellularized bone particles(Iop Publishing Ltd, 2024) Kara, Aylin; Distler, Thomas; Akkineni, Ashwini Rahul; Tihminlioglu, Funda; Gelinsky, Michael; Boccaccini, Aldo R.One of the key challenges in biofabrication applications is to obtain bioinks that provide a balance between printability, shape fidelity, cell viability, and tissue maturation. Decellularization methods allow the extraction of natural extracellular matrix, preserving tissue-specific matrix proteins. However, the critical challenge in bone decellularization is to preserve both organic (collagen, proteoglycans) and inorganic components (hydroxyapatite) to maintain the natural composition and functionality of bone. Besides, there is a need to investigate the effects of decellularized bone (DB) particles as a tissue-based additive in bioink formulation to develop functional bioinks. Here we evaluated the effect of incorporating DB particles of different sizes (<= 45 and <= 100 mu m) and concentrations (1%, 5%, 10% (wt %)) into bioink formulations containing gelatin (GEL) and pre-osteoblasts (MC3T3-E1) or human mesenchymal stem cells (hTERT-MSCs). In addition, we propose a minimalistic bioink formulation using GEL, DB particles and cells with an easy preparation process resulting in a high cell viability. The printability properties of the inks were evaluated. Additionally, rheological properties were determined with shear thinning and thixotropy tests. The bioprinted constructs were cultured for 28 days. The viability, proliferation, and osteogenic differentiation capacity of cells were evaluated using biochemical assays and fluorescence microscopy. The incorporation of DB particles enhanced cell proliferation and osteogenic differentiation capacity which might be due to the natural collagen and hydroxyapatite content of DB particles. Alkaline phosphatase activity is increased significantly by using DB particles, notably, without an osteogenic induction of the cells. Moreover, fluorescence images display pronounced cell-material interaction and cell attachment inside the constructs. With these promising results, the present minimalistic bioink formulation is envisioned as a potential candidate for bone tissue engineering as a clinically translatable material with straightforward preparation and high cell activity.Review Citation - WoS: 17Citation - Scopus: 16Engineering Periodontal Tissue Interfaces Using Multiphasic Scaffolds and Membranes for Guided Bone and Tissue Regeneration(Elsevier, 2024) Özkendir, Özge; Karaca, İlayda; Çullu, Selin; Yaşar, Hüsniye Nur,; Erdoğan, Oğulcan; Dikici, Serkan; Dikici, Betul AldemirPeriodontal diseases are one of the greatest healthcare burdens worldwide. The periodontal tissue compartment is an anatomical tissue interface formed from the periodontal ligament, gingiva, cementum, and bone. This multifaceted composition makes tissue engineering strategies challenging to develop due to the interface of hard and soft tissues requiring multiphase scaffolds to recreate the native tissue architecture. Multilayer constructs can better mimic tissue interfaces due to the individually tuneable layers. They have different characteristics in each layer, with modulation of mechanical properties, material type, porosity, pore size, morphology, degradation properties, and drug-releasing profile all possible. The greatest challenge of multilayer constructs is to mechanically integrate consecutive layers to avoid delamination, especially when using multiple manufacturing processes. Here, we review the development of multilayer scaffolds that aim to recapitulate native periodontal tissue interfaces in terms of physical, chemical, and biological characteristics. Important properties of multiphasic biodegradable scaffolds are highlighted and summarised, with design requirements, biomaterials, and fabrication methods, as well as post-treatment and drug/growth factor incorporation discussed.Article Citation - WoS: 6Citation - Scopus: 6Microbial Desalination Cell Treated Spent Geothermal Brine as a Nutrient Medium in Hydroponic Lettuce Cultivation: Health Risk Assessment(Elsevier, 2024) Goren, A. Y.; Eskisoy, D. N.; Genisoglu, S.; Okten, H. E.The scarcity and contamination of freshwater resources are extremely critical issues today, and the expansion of water reuse has been considered as an option to decrease its impact. Therefore, the reuse of microbial desalination (MDC)-treated spent geothermal brine for agricultural purposes arises as a good solution to prevent water contamination and provide sustainable water usage. In this study, the potential of treated spent geothermal water from MDC system as a nutrient solution for the hydroponic cultivation of lettuce was evaluated. The effects of different water samples (Hoagland solution (R1) as a control, MDC-treated water (R2), 1:1, v/v mixture of MDCtreated water and Hoagland solution (R3), 4:1, v/v mixture of MDC-treated water and Hoagland solution (R4), and tap water (R5)) on lettuce growth were considered. The application of R3 and R4 samples for hydroponic lettuce cultivation was promising since the lettuce plants uptake sufficient nutrients for their growth and productivity with low toxic metal concentrations. In addition, the chlorophyll-a, chlorophyll-b, and carotene contents of lettuce were in the range of 1.045-2.391 mg/g, 0.761-1.986 mg/g, and 0.296-0.423 mg/g in different water samples, respectively. The content of chlorophyll-a was highest in R1 (2.391 mg/g), followed by R3 (2.371 mg/g). Furthermore, the health risk assessment of heavy metal accumulations in the lettuce plants cultivated in the various water samples was determined. Results showed that heavy metal exposure via lettuce consumption is unlikely to suffer noticeable adverse health problems with values below the permissible limit value.Article Citation - WoS: 17Citation - Scopus: 15Antiproliferative and Apoptotic Effects of Olive Leaf Extract Microcapsules on Mcf-7 and A549 Cancer Cells(American Chemical Society, 2023) Bal, Yıldız; Sürmeli, Yusuf; Şanlı Mohamed, GülşahAlginate microcapsules are a talented means for the delivery of broad curative biomacromolecules. In this study, we immobilized olive leaf extract (OLE) by calcium alginate (CA) and chitosan-coated CA (CCA) and characterized the OLE-loaded CA and CCA. The cytotoxic effect, the cell cycle arrest, and the apoptotic effect of OLE and its microcapsules were investigated against breast adenocarcinoma (MCF-7) and lung carcinoma (A549). As a result, the loading capacity of OLE-CA and OLE-CCA was found to be 80 and 99%, respectively, in optimal conditions. Also, OLE-CA and OLE-CCA were characterized by unique FTIR peaks and morphological display relative to the empty CCA microcapsules. The cytotoxicity analysis showed that the IC50 values of OLE-CA and OLE-CCA were determined to be 312 and 0.94 μg mL-1 against A549, respectively, whereas these were found to be 865.4 and 425.5 μg mL-1 for MCF-7 cells. On the other hand, the OLE microcapsules did not possess in any concentration of cytotoxic influence on the BEAS 2B healthy cell line. Also, the exposure of OLE-CCA to MCF-7 and A549 resulted in the arrest of more MCF-7 and A549 cells at the G0/G1 phase compared to the OLE. A549 and MCF-7 cells were predominantly found in the late apoptosis phase and necrosis phase, respectively. Optical microscopy images confirmed that OLE microcapsules were more effective against MCF-7 and A549 than free OLE. The present work suggested that the OLE microcapsules might be administered as nutrition supplements for cancer therapy. © 2023 The Authors. Published by American Chemical Society.Article Citation - WoS: 6Citation - Scopus: 5Basidiomycota Species in Drosophila Gut Are Associated With Host Fat Metabolism(Nature Research, 2023) Bozkurt, Berkay; Terlemez, Gamze; Sezgin, EfeThe importance of bacterial microbiota on host metabolism and obesity risk is well documented. However, the role of fungal microbiota on host storage metabolite pools is largely unexplored. We aimed to investigate the role of microbiota on D. melanogaster fat metabolism, and examine interrelatedness between fungal and bacterial microbiota, and major metabolic pools. Fungal and bacterial microbiota profiles, fat, glycogen, and trehalose metabolic pools are measured in a context of genetic variation represented by whole genome sequenced inbred Drosophila Genetic Reference Panel (DGRP) samples. Increasing Basidiomycota, Acetobacter persici, Acetobacter pomorum, and Lactobacillus brevis levels correlated with decreasing triglyceride levels. Host genes and biological pathways, identified via genome-wide scans, associated with Basidiomycota and triglyceride levels were different suggesting the effect of Basidiomycota on fat metabolism is independent of host biological pathways that control fungal microbiota or host fat metabolism. Although triglyceride, glycogen and trehalose levels were highly correlated, microorganisms’ effect on triglyceride pool were independent of glycogen and trehalose levels. Multivariate analyses suggested positive interactions between Basidiomycota, A. persici, and L. brevis that collectively correlated negatively with fat and glycogen pools. In conclusion, fungal microbiota can be a major player in host fat metabolism. Interactions between fungal and bacterial microbiota may exert substantial control over host storage metabolite pools and influence obesity risk. © 2023, Springer Nature Limited.Article Citation - WoS: 2Citation - Scopus: 6Immobilization of Olive Leaf Extract With Chitosan Nanoparticles as an Adjunct To Enhance Cytotoxicity(American Chemical Society, 2023) Özdamar, Burcu; Sürmeli, Yusuf; Şanlı Mohamed, GülşahWe immobilized the olive leaf extract (OLE) with chitosannanoparticles(CNPs) by optimizing the effect of various immobilization conditions,and OLE-loaded CNPs (OLE-CNPs) were then elaborately characterizedphysicochemically by scanning electron microscopy (SEM), Fourier transforminfrared (FT-IR) spectroscopy, dynamic light scattering (DLS), andatomic force microscopy (AFM). Under optimal conditions, CNPs wereable to accommodate the OLE with a loading capacity of 97.5%. Theresulting OLE-CNPs had a spherical morphology, and their average diameterwas approximately 100 nm. The cytotoxic influence, cell cycle distribution,and apoptosis stage of OLE and OLE-CNPs were analyzed on lung carcinoma(A549) and breast adenocarcinoma (MCF-7) cell lines. In an in vitrocytotoxic assay, IC50 values of OLE-CNPs were determinedto be 540 & mu;g/mL for A549 and 810 & mu;g/mL for MCF-7. Thetreatment of both A549 and MCF-7 with OLE-CNPs caused the highestcell arrest in G0/G1 in a dose-independent manner. OLE-CNPs affectedcell cycle distribution in a manner different from free OLE treatmentin both cancer cells. A549 and MCF-7 cells were predominantly foundin the late apoptosis and necrosis phases, respectively, upon treatmentof 1000 & mu;M OLE-CNPs. Our results suggest that CNPs enhance theutility of OLEs as nutraceuticals in cancer and that OLE-CNPs canbe utilized as an adjunct to cancer therapy.Article Citation - WoS: 8Citation - Scopus: 9Development of Plant-Based Biopolymer Coatings for 3d Cell Culture: Boron-Silica Quince Seed Mucilage Nanocomposites(Royal Society of Chemistry, 2023) Yılmaz, Hilal Deniz; Cengiz, Uğur; Derkuş, Burak; Arslan, Yavuz EmreSpheroid formation with spontaneous aggregation has captured interest in most cell culture studies due to its easy set-up and more reliable results. However, the economic and technical costs of the advanced systems and commercial ultra-low adhesive platforms have pushed researchers into pursuing alternatives. Nowadays, polymeric coatings, including poly-hydroxyethyl methacrylate and agar/agarose, are the commonly used polymers for non-adhesive plate fabrication, yet the costs and working solvent or heat-dependent preparation procedures maintain the need for the development of novel biomaterials. Here, we propose a greener and more economical approach for producing non-adherent surfaces and spheroid formation. For this, a plant waste-based biopolymer from quince fruit (Cydonia oblonga Miller, from Rosaceae family) seeds and boron-silica precursors were introduced. The unique water-holding capacity of quince seed mucilage (Q) was enriched with silanol and borate groups to form bioactive and hydrophilic nanocomposite overlays for spheroid studies. Moreover, 3D gel plates from the nanocomposite material were fabricated and tested in vitro as a proof-of-concept. The surface properties of coatings and the biochemical and mechanical properties of the nanocomposite materials were evaluated in-depth with techniques, and extra hydrophilic coatings were obtained. Three different cell lines were cultured on these nanocomposite surfaces, and spheroid formation with increased cellular viability was recorded on day 3 with a >200 & mu;m spheroid size. Overall, Q-based nanocomposites are believed to be a fantastic alternative for non-adherent surface fabrication due to their low-cost, easy operation, and intrinsic hydration layer forming capacity with biocompatible nature in vitro.Article Citation - WoS: 27Citation - Scopus: 27In Vivo Bone Regeneration Capacity of Multiscale Porous Polycaprolactone-Based High Internal Phase Emulsion (polyhipe) Scaffolds in a Rat Calvarial Defect Model(American Chemical Society, 2023) Aldemir Dikici, Betül; Chen, Min-Chia; Dikici, Serkan; Chiu, Hsien-Chung; Claeyssens, FrederikGlobally, one of the most common tissue transplantationproceduresis bone grafting. Lately, we have reported the development of polymerizedhigh internal phase emulsions (PolyHIPEs) made of photocurable polycaprolactone(4PCLMA) and shown their potential to be used as bone tissue engineeringscaffolds in vitro. However, it is essential to evaluatethe in vivo performance of these scaffolds to investigatetheir potential in a clinically more relevant manner. Therefore, inthis study, we aimed to compare in vivo performancesof macroporous (fabricated using stereolithography), microporous (fabricatedusing emulsion templating), and multiscale porous (fabricated usingemulsion templating and perforation) scaffolds made of 4PCLMA. Also,3D-printed macroporous scaffolds (fabricated using fused depositionmodeling) made of thermoplastic polycaprolactone were used as a control.Scaffolds were implanted into a critical-sized calvarial defect, animalswere sacrificed 4 or 8 weeks after implantation, and the new boneformation was assessed by micro-computed tomography, dental radiography,and histology. Multiscale porous scaffolds that include both micro-and macropores resulted in higher bone regeneration in the defectarea compared to only macroporous or only microporous scaffolds. Whenone-grade porous scaffolds were compared, microporous scaffolds showedbetter performance than macroporous scaffolds in terms of mineralizedbone volume and tissue regeneration. Micro-CT results revealed thatwhile bone volume/tissue volume (Bv/Tv) values were 8 and 17% at weeks4 and 8 for macroporous scaffolds, they were significantly higherfor microporous scaffolds, with values of 26 and 33%, respectively.Taken together, the results reported in this study showed the potentialapplication of multiscale PolyHIPE scaffolds, in particular, as apromising material for bone regeneration.Review Citation - WoS: 52Citation - Scopus: 56Spheroid engineering in microfluidic devices(American Chemical Society, 2023) Tevlek, Atakan; Keçili, Seren; Özçelik, Özge Solmaz; Kulah, Haluk; Tekin, H. CumhurTwo-dimensional (2D) cell culture techniques are commonly employed to investigate biophysical and biochemical cellular responses. However, these culture methods, having monolayer cells, lack cell-cell and cell-extracellular matrix interactions, mimicking the cell microenvironment and multicellular organization. Three-dimensional (3D) cell culture methods enable equal transportation of nutrients, gas, and growth factors among cells and their microenvironment. Therefore, 3D cultures show similar cell proliferation, apoptosis, and differentiation properties to in vivo. A spheroid is defined as self-assembled 3D cell aggregates, and it closely mimics a cell microenvironment in vitro thanks to cell-cell/matrix interactions, which enables its use in several important applications in medical and clinical research. To fabricate a spheroid, conventional methods such as liquid overlay, hanging drop, and so forth are available. However, these labor-intensive methods result in low-throughput fabrication and uncontrollable spheroid sizes. On the other hand, microfluidic methods enable inexpensive and rapid fabrication of spheroids with high precision. Furthermore, fabricated spheroids can also be cultured in microfluidic devices for controllable cell perfusion, simulation of fluid shear effects, and mimicking of the microenvironment-like in vivo conditions. This review focuses on recent microfluidic spheroid fabrication techniques and also organ-on-a-chip applications of spheroids, which are used in different disease modeling and drug development studies.Article Citation - WoS: 23Citation - Scopus: 26Fish scale containing alginate dialdehyde-gelatin bioink for bone tissue engineering(IOP Publishing Ltd, 2023) Özenler, Aylin Kara; Distler, Thomas; Tıhmınlıoğlu, Funda; Boccaccini, Aldo RThe development of biomaterial inks suitable for biofabrication and mimicking the physicochemical properties of the extracellular matrix is essential for the application of bioprinting technology in tissue engineering (TE). The use of animal-derived proteinous materials, such as jellyfish collagen, or fish scale (FS) gelatin (GEL), has become an important pillar in biomaterial ink design to increase the bioactivity of hydrogels. However, besides the extraction of proteinous structures, the use of structurally intact FS as an additive could increase biocompatibility and bioactivity of hydrogels due to its organic (collagen) and inorganic (hydroxyapatite) contents, while simultaneously enhancing mechanical strength in three-dimensional (3D) printing applications. To test this hypothesis, we present here a composite biomaterial ink composed of FS and alginate dialdehyde (ADA)-GEL for 3D bioprinting applications. We fabricate 3D cell-laden hydrogels using mouse pre-osteoblast MC3T3-E1 cells. We evaluate the physicochemical and mechanical properties of FS incorporated ADA-GEL biomaterial inks as well as the bioactivity and cytocompatibility of cell-laden hydrogels. Due to the distinctive collagen orientation of the FS, the compressive strength of the hydrogels significantly increased with increasing FS particle content. Addition of FS also provided a tool to tune hydrogel stiffness. FS particles were homogeneously incorporated into the hydrogels. Particle-matrix integration was confirmed via scanning electron microscopy. FS incorporation in the ADA-GEL matrix increased the osteogenic differentiation of MC3T3-E1 cells in comparison to pristine ADA-GEL, as FS incorporation led to increased ALP activity and osteocalcin secretion of MC3T3-E1 cells. Due to the significantly increased stiffness and supported osteoinductivity of the hydrogels, FS structure as a natural collagen and hydroxyapatite source contributed to the biomaterial ink properties for bone engineering applications. Our findings indicate that ADA-GEL/FS represents a new biomaterial ink formulation with great potential for 3D bioprinting, and FS is confirmed as a promising additive for bone TE applications.