Bioengineering / Biyomühendislik
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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: 30Citation - Scopus: 33Molecular Separation by Using Active and Passive Microfluidic Chip Designs: a Comprehensive Review(Wiley, 2023) Ebrahimi, Aliakbar; Didarian, Reza; Shih, Chih-Hsin; Nasseri, Behzad; Ethan Li, Yi-Chen; Shih, Steven; İçöz, Kutay; Tarım, Ergün Alperay; Akpek, Ali; Çeçen, Berivan; Bal Öztürk, Ayça; Güleç, Kadri; Tarım, Burcu Sırma; Tekin, Hüseyin CumhurSeparation and identification of molecules and biomolecules such as nucleic acids, proteins, and polysaccharides from complex fluids are known to be important due to unmet needs in various applications. Generally, many different separation techniques, including chromatography, electrophoresis, and magnetophoresis, have been developed to identify the target molecules precisely. However, these techniques are expensive and time consuming. “Lab-on-a-chip” systems with low cost per device, quick analysis capabilities, and minimal sample consumption seem to be ideal candidates for separating particles, cells, blood samples, and molecules. From this perspective, different microfluidic-based techniques have been extensively developed in the past two decades to separate samples with different origins. In this review, “lab-on-a-chip” methods by passive, active, and hybrid approaches for the separation of biomolecules developed in the past decade are comprehensively discussed. Due to the wide variety in the field, it will be impossible to cover every facet of the subject. Therefore, this review paper covers passive and active methods generally used for biomolecule separation. Then, an investigation of the combined sophisticated methods is highlighted. The spotlight also will be shined on the elegance of separation successes in recent years, and the remainder of the article explores how these permit the development of novel techniques. © 2023 The Authors. Advanced Materials Interfaces published by Wiley-VCH GmbH.Book Part Citation - Scopus: 3Tissue Engineering Applications of Marine-Based Materials(Springer, 2022) Polat, Hürriyet; Zeybek, Nuket; Polat, MehmetTissue engineering is a promising approach in replacing or improving tissues lost or has become nonviable due to disease or trauma by the use of scaffold materials by combining engineering and biochemical/physicochemical methods. Its purpose is to create suitable matrices that support cell differentiation and proliferation toward the formation of new and functional tissue. Marine-based natural compounds are potential scaffold feedstock material in tissue engineering owing to their biocompatibility and biodegradability while providing excellent biochemical/physicochemical properties. Numerous application areas and various fabrication routes techniques described in the literature attest to the importance of these materials in tissue regeneration. This review has been carried to merge the information from a large number of studies on the marine-based scaffold materials in tissue engineering into a coherent summary. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.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.Article Citation - WoS: 6Citation - Scopus: 7Designing Robust Xylan/Chitosan Composite Shells Around Drug-Loaded Msns: Stability in Upper Git and Degradation in the Colon Microbiota(Elsevier, 2023) Zeybek, Nüket; Büyükkileci, Ali Oğuz; Güleç, Şükrü; Polat, Mehmet; Polat, Hürriyetong residence times, near-neutral pH values, and release triggered by the enzymatic action of the resident microbiota offer unique opportunities for improved drug delivery in the colon. The fact that a delivery agent must also pass through the complete GI tract without degradation presents a challenge due to widely changing pH conditions. In this study, a promising colon-targeted drug delivery system was composed of a xylan/chitosan composite shell formed on curcumin-loaded mesoporous silica nanoparticles (MSNs). A novel synthesis approach was employed to facilitate precipitation of negatively charged xylan on negatively charged MSNs by concurrent chitosan polymerization. Curcumin-loaded xylan/chitosan-coated MSNs (C-MSNs) were determined to contain nearly 42% xylan by the inclusion of chitosan in a one-to-one ratio with xylan. The xylan/chitosan composite shell demonstrated excellent stability in the acidic upper GI tract. The hydrolysis of glycosidic bonds by resident microbiota was the triggering mechanism for xylan degradation and curcumin release in the colon. The presence of xylan has the further benefit of increasing the number of beneficial bacteria and improving short-chain fatty acid production for improved colon health.Article Citation - WoS: 51Citation - Scopus: 583d Printed Gelatin/Decellularized Bone Composite Scaffolds for Bone Tissue Engineering: Fabrication, Characterization and Cytocompatibility Study(Elsevier, 2022) Kara, Aylin; Distler, Thomas; Polley, Christian; Schneidereit, Dominik; Seitz, Hermann; Friedrich, Oliver; Tıhmınlıoğlu, Funda; Boccaccini, Aldo RThree-dimensional (3D) printing technology enables the design of personalized scaffolds with tunable pore size and composition. Combining decellularization and 3D printing techniques provides the opportunity to fabricate scaffolds with high potential to mimic native tissue. The aim of this study is to produce novel decellularized bone extracellular matrix (dbECM)-reinforced composite-scaffold that can be used as a biomaterial for bone tissue engineering. Decellularized bone particles (dbPTs, ∼100 μm diameter) were obtained from rabbit femur and used as a reinforcement agent by mixing with gelatin (GEL) in different concentrations. 3D scaffolds were fabricated by using an extrusion-based bioprinter and crosslinking with microbial transglutaminase (mTG) enzyme, followed by freeze-drying to obtain porous structures. Fabricated 3D scaffolds were characterized morphologically, mechanically, and chemically. Furthermore, MC3T3-E1 mouse pre-osteoblast cells were seeded on the dbPTs reinforced GEL scaffolds (GEL/dbPTs) and cultured for 21 days to assess cytocompatibility and cell attachment. We demonstrate the 3D-printability of dbPTs-reinforced GEL hydrogels and the achievement of homogenous distribution of the dbPTs in the whole scaffold structure, as well as bioactivity and cytocompatibility of GEL/dbPTs scaffolds. It was shown that Young's modulus and degradation rate of scaffolds were enhanced with increasing dbPTs content. Multiphoton microscopy imaging displayed the interaction of cells with dbPTs, indicating attachment and proliferation of cells around the particles as well as into the GEL-particle hydrogels. Our results demonstrate that GEL/dbPTs hydrogel formulations have potential for bone tissue engineering.Article Citation - WoS: 25Citation - Scopus: 33Novel Phytochemical Cissus Quadrangularis Extract-Loaded Chitosan/Na-carboxymethyl Cellulose-Based Scaffolds for Bone Regeneration(SAGE Publications, 2018) Tamburacı, Sedef; Kimna, Ceren; Tıhmınlıoğlu, FundaMedicinal plants are attracting considerable interest as a potential therapeutic agent for bone tissue regeneration. Cissus quadrangularis L. is also a medicinal plant known with its osteogenic activity. In this study, a phytochemical scaffold was produced by incorporating Cissus quadrangularis with chitosan/Na-carboxymethyl cellulose blend by lyophilization technique. The effect of Cissus quadrangularis loading on the mechanical, morphological, chemical, and degradation properties as well as in vitro cytotoxicity, cell proliferation, and differentiation of the composites was investigated. Scanning electron microscopy images showed that porous Cissus quadrangularis-loaded scaffolds were obtained with an average pore size of 148-209 mu m which is appropriate for bone regeneration. Cissus quadrangularis incorporation enhanced the compression modulus of scaffolds from 76 to 654 kPa. In vitro cell culture results indicated that Cissus quadrangularis/chitosan/Na-carboxymethyl cellulose scaffolds provided a favorable substrate for the osteoblast adhesion, proliferation, and mineralization. Results supported the osteoinductive property of the Cissus quadrangularis extract-incorporated scaffolds even without osteogenic media supplement. Cissus quadrangularis extract increased the alkaline phosphatase activity of the SaOS-2 cells on scaffolds on 7th and 14th days of incubation. The investigation of characterization and cell culture studies suggest that Cissus quadrangularis-loaded osteoinductive Cissus quadrangularis/chitosan/Na-carboxymethyl cellulose scaffold can serve as a potential biomaterial for bone tissue engineering applications.Article Citation - WoS: 18Citation - Scopus: 17Cnt Incorporated Polyacrilonitrile/Polypyrrole Nanofibers as Keratinocytes Scaffold(Trans Tech Publications, 2019) İnce Yardımcı, Atike; Aypek, Hande; Öztürk, Özgür; Yılmaz, Selahattin; Özçivici, Engin; Meşe, Gülistan; Selamet, YusufPolypyrrole (PPy) is an attractive scaffold material for tissue engineering with its non-toxic and electrically conductive properties. There has not been enough information about PPy usage in skin tissue engineering. The aim of this study is to investigate biocompatibility of polyacrilonitrile (PAN)/PPy nanofibrous scaffold for human keratinocytes. PAN/PPy bicomponent nanofibers were prepared by electrospinning, in various PPy concentrations and with carbon nanotube (CNT) incorporation. The average diameter of electrospun nanofibers decreased with increasing PPy concentration. Further, agglomerated CNTs caused beads and disordered parts on the surface of nanofibers. Biocompatibility of these PAN/PPy and PAN/PPy/CNT scaffolds were analyzed in vitro. Both scaffolds provided adhesion and proliferation of keratinocytes. Nanofiber diameter did not significantly influence the morphology of cells. However, with increasing number of cells, cells stayed among nanofibers and this affected their shape and size. In this study, we demonstrated that PAN/PPy and PAN/PPy/CNT scaffolds enabled the growth of keratinocytes, showing their biocompatibility.Article Citation - WoS: 5Citation - Scopus: 6Efficient Synthesis of Crgd Functionalized Polymers as Building Blocks of Targeted Drug Delivery Systems(Elsevier Ltd., 2018) Thankappan, Hajeeth; Zelçak, Aykut; Taykoz, Damla; Bulmuş, VolgaSynthetic peptides with cyclic arginine-glycine-aspartate motif (cRGD) play an important role in cell recognition and cell adhesion. cRGD-decorated soluble polymers and polymeric nanoparticles have been increasingly used for cell-specific delivery of antitumor drugs. While the significance of cRGD modification for tumor cell-specific targeting of polymeric carriers is well-accepted, straightforward procedures ensuring the fidelity of cRGD modification of polymeric systems are still lacking. Herein, we have reported an in-situ polymerization approach for synthesis of cRGD-end-functionalized well-defined polymers as potential building blocks of targeted drug delivery systems. A new cRGD peptide functionalized RAFT agent was synthesized as confirmed by MALDI-TOF and 1H NMR spectroscopy. The ability of this RAFT agent to control polymerizations was then tested using two different monomers oligoethyleneglycol acrylate and t-butyl methacrylate. The RAFT-controlled character of polymerizations and the living characteristic of the synthesized polymers were investigated through a series of kinetic experiments. The cytotoxicity and targeting capability of cRGD-functionalized OEGA polymers were investigated using cell lines expressing αvβ3 integrins at varying extents.Article Citation - WoS: 65Citation - Scopus: 72Effect of Peg Grafting Density and Hydrodynamic Volume on Gold Nanoparticle-Cell Interactions: an Investigation on Cell Cycle, Apoptosis, and Dna Damage(American Chemical Society, 2016) Uz, Metin; Bulmuş, Volga; Alsoy Altınkaya, SacideIn this study, interactions of polyethylene glycol (PEG)-coated gold nanoparticles (AuNPs) with cells were investigated with particular focus on the relationship between the PEG layer properties (conformation, grafting density, and hydrodynamic volume) and cell cycle arrest, apoptosis, and DNA damage. Steric hindrance and PEG hydrodynamic volume controlled the protein adsorption, whereas the AuNP core size and PEG hydrodynamic volume were primary factors for cell uptake and viability. At all PEG grafting densities, the particles caused significant cell cycle arrest and DNA damage against CaCo2 and PC3 cells without apoptosis. However, at a particular PEG grafting density (∼0.65 chains/nm2), none of these severe damages were observed on 3T3 cells indicating discriminating behavior of the healthy (3T3) and cancer (PC3 and CaCo2) cells. It was concluded that the PEG grafting density and hydrodynamic volume, tuned with the PEG concentration and AuNP size, played an important role in particle-cell interactions.