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.Article Citation - WoS: 25Citation - Scopus: 30Fabrication of 3d Printed Poly(lactic Acid) Strut and Wet-Electrospun Cellulose Nano Fiber Reinforced Chitosan-Collagen Hydrogel Composite Scaffolds for Meniscus Tissue Engineering(SAGE Publications, 2022) Güneş, Oylum Çolpankan; Kara, Aylin; Baysan, Gizem; Hüsemoğlu, Reşit Buğra; Akokay, Pınar; Ziylan Albayrak, Aylin; Ergür, Bekir Uğur; Havitçioğlu, HasanThe main goal of the study was to produce chitosan-collagen hydrogel composite scaffolds consisting of 3D printed poly(lactic acid) (PLA) strut and nanofibrous cellulose for meniscus cartilage tissue engineering. For this purpose, first PLA strut containing microchannels was incorporated into cellulose nanofibers and then they were embedded into chitosan-collagen matrix to obtain micro- and nano-sized topographical features for better cellular activities as well as mechanical properties. All the hydrogel composite scaffolds produced by using three different concentrations of genipin (0.1, 0.3, and 0.5%) had an interconnected microporous structure with a swelling ratio of about 400% and water content values between 77 and 83% which is similar to native cartilage extracellular matrix. The compressive strength of all the hydrogel composite scaffolds was found to be similar (∼32 kPa) and suitable for cartilage tissue engineering applications. Besides, the hydrogel composite scaffold comprising 0.3% (w/v) genipin had the highest tan δ value (0.044) at a frequency of 1 Hz which is around the walking frequency of a person. According to the in vitro analysis, this hydrogel composite scaffold did not show any cytotoxic effect on the rabbit mesenchymal stem cells and enabled cells to attach, proliferate and also migrate through the inner area of the scaffold. In conclusion, the produced hydrogel composite scaffold holds great promise for meniscus tissue engineering.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 Lif Kabağı Takviye Edilmiş Kitosan-ipek Hidrojel Kompozit Doku İskelelerinin Kıkırdak Doku Hasarı Tedavisinde Kullanımının Araştırılması(2021) Çolpankan Güneş, Oylum; Özer, İbrahim Erkut; Kara, Aylin; Ziylan Albayrak, Aylin; Havıtçıoğlu, HasanKıkırdak doku hasarlarının onarılmasındaki mevcut tedaviler, kıkırdağın kendi kendini iyileştirme kapasitesinin düşük olması nedeni ile sınırlıdır. Son yıllarda doku mühendisliği, kıkırdak rejenerasyonu için umut verici bir yaklaşım olarak önerilmektedir. Bu çalışmada, kıkırdak doku hasarları için lif kabağı ile güçlendirilmiş ipek fibroin/kitosan hidrojeller hazırlanmıştır. Biyouyumlu, biyolojik olarak parçalanabilir ipek fibroin ve kitosan polimerleri, doğal ve toksik olmayan bir çapraz bağlama maddesi olan genipin ile çapraz bağlanmıştır. Taramalı elektron mikroskobu (SEM) ve Fourier Dönüşümü Kızılötesi Spektroskopisi (FTIR) sırasıyla morfoloji ve kimyasal yapı karakterizasyonu için kullanılmıştır. Viskoelastik özelliklerin belirlenmesi için dinamik mekanik analiz cihazı (DMA) kullanılırken, iskelelerin mekanik özelliklerini incelemek için basma testi kullanılmıştır. Doku iskelelerinin sitotoksisitesi, hücre canlılığı ve çoğalması tavşan mezenkimal kök hücreleri kullanılarak LDH, WST ve kollajen testi ile araştırılmıştır. Üretilen hidrojel kompozit doku iskelelerinin tamamının birbirine bağlı mikro gözenekli bir yapıya sahip olduğu ve lif kabaklarının yapıya iyi entegre olduğu görülmektedir. Ağırlıkça %0,3 genipin ile çapraz bağlanan hidrojel kompozit doku iskelesi (L-CSG3), eklem kıkırdağıyla karşılaştırılabilir su içeriği (94,4±% 0,2), tan ? (1 Hz'de 0,18) ve basma modülü (5,5 MPa) değerleri göstermiştir. Ayrıca, in-vitro test sonuçlarına göre, bu hidrojel kompozit doku iskelesi, tavşan mezenkimal kök hücrelerinde gelişmiş canlılık göstermiştir. Sonuç olarak, bu hidrojel kompozit doku iskelesi, kıkırdak dokusu rejenerasyonu için umut vaat ettiği söylenebilir.Article Citation - WoS: 14Citation - Scopus: 14Development of Biological Meniscus Scaffold: Decellularization Method and Recellularization With Meniscal Cell Population Derived From Mesenchymal Stem Cells(SAGE Publications, 2021) Kara, Aylin; Koçtürk, Semra; Bilici, Gökçen; Havıtçıoğlu, HasanTissue engineering approaches which include a combination of cells and scaffold materials provide an alternative treatment for meniscus regeneration. Decellularization and recellularization techniques are potential treatment options for transplantation. Maintenance of the ultrastructure composition of the extracellular matrix and repopulation with cells are important factors in constructing a biological scaffold and eliminating immunological reactions. The aim of the study is to develop a method to obtain biological functional meniscus scaffolds for meniscus regeneration. For this purpose, meniscus tissue was decellularized by our modified method, a combination of physical, chemical, and enzymatic methods and then recellularized with a meniscal cell population composed of fibroblasts, chondrocytes and fibrochondrocytes that obtained from mesenchymal stem cells. Decellularized and recellularized meniscus scaffolds were analysed biochemically, biomechanically and histologically. Our results revealed that cellular components of the meniscus were successfully removed by preserving collagen and GAG structures without any significant loss in biomechanical properties. Recellularization results showed that the meniscal cells were localized in the empty lacuna on the decellularized meniscus, and also well distributed and proliferated consistently during the cell culture period (p < 0.05). Furthermore, a high amount of DNA, collagen, and GAG contents (p < 0.05) were obtained with the meniscal cell population in recellularized meniscus tissue. The study demonstrates that our decellularization and recellularization methods were effective to develop a biological functional meniscus scaffold and can mimic the meniscus tissue with structural and biochemical features. We predict that the obtained biological meniscus scaffolds may provide avoidance of adverse immune reactions and an appropriate microenvironment for allogeneic or xenogeneic recipients in the transplantation process. Therefore, as a promising candidate, the obtained biological meniscus scaffolds might be verified with a transplantation experiment.Article Citation - WoS: 14Citation - Scopus: 17Biocompatibility of Silicon Nitride Produced Via Partial Sintering & Tape Casting(Elsevier Ltd., 2021) Çeçen, Berivan; Topateş, Gülsüm; Kara, Aylin; Akbulut, Serdar Onat; Havıtçıoğlu, Hasan; Kozacı, Leyla DidemThe biocompatibility of silicon nitride ceramics was proven by several studies however this study is apart from the literature in the manner of production routes that are tape casting and partial sintering. We report the tape casting route was chosen and a porous structure was obtained by partial sintering technique. Tape casting brought a smooth surface to the samples. Density and pore size distribution analysis showed that the scaffolds have low density because of the porous structure. XRD and SEM analyses were carried out to reveal the phase and microstructural characteristics of porous ceramic samples. Static contact angle measurement was done for the characterization of the wettability of the scaffolds. It revealed that the surface of the scaffolds was highly hydrophilic which is a desirable characteristic for the protein and cell adhesion. The mechanical characteristics of the scaffolds were analyzed by compression tests. Human osteosarcoma cells were used for in vitro studies. Cell-proliferation and cytotoxicity were analyzed by WST-1 and LDH, respectively. The osteoblastic behavior of the cells on the surface of the scaffolds was identified by alkaline phosphatase activity. BCA analysis was used for total protein content. The BCA and ALP results showed an increasing trend which is directly correlated with cell proliferation. Cells on the surface of the silicon nitride scaffolds were visualized by SEM and fluorescence microscopy where the images supported the in vitro analysis. Therefore, porous silicon nitride scaffolds fabricated via tape casting and partial sintering were biocompatible and they are possible candidates as bone substitute elements. © 2020 Elsevier Ltd and Techna Group S.r.l.Article Citation - WoS: 12Citation - Scopus: 17Fish Scale/Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Nanofibrous Composite Scaffolds for Bone Regeneration(SAGE Publications, 2020) Kara, Aylin; Güneş, Oylum C.; Albayrak, Aylin Z.; Bilici, Gökçen; Erbil, Güven; Havitcioğlu, HasanThe aim of this study was to produce three-dimensional, nanofibrous fish scale/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) composite scaffolds as bone filling materials. This is the first report wherein fish scales were used within a nanofibrous matrix for bone regeneration. Composite scaffolds with a cotton wool-like structure (fiber diameter: 560 +/- 64 nm; porosity: 82%) were obtained by incorporating chopped fish scales into wet-electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nanofibers and freeze-drying. The addition of the fish scales improved the mechanical properties, biomineralization tendency, cell viability, alkaline phosphatase activity, and type I collagen production. Consequently, produced composite scaffolds would be regarded to have the therapeutic capacity in bone tissue damages.