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Publication Metadata only 3D bioprinted glioma models(Iop Publishing Ltd, 2022) N/A; N/A; N/A; N/A; N/A; N/A; N/A; Department of Mechanical Engineering; Yığcı, Defne; Sarabi, Misagh Rezapour; Üstün, Merve; Atçeken, Nazente; Sokullu, Emel; Önder, Tuğba Bağcı; Taşoğlu, Savaş; Undergraduate Student; PhD Student; PhD Student; Researcher; Faculty Member; Faculty Member; Faculty Member; Department of Mechanical Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; N/A; School of Medicine; School of Medicine; College of Engineering; N/A; N/A; N/A; N/A; 163024; 184359; 291971Glioma is one of the most malignant types of cancer and most gliomas remain incurable. One of the hallmarks of glioma is its invasiveness. Furthermore, glioma cells tend to readily detach from the primary tumor and travel through the brain tissue, making complete tumor resection impossible in many cases. To expand the knowledge regarding the invasive behavior of glioma, evaluate drug resistance, and recapitulate the tumor microenvironment, various modeling strategies were proposed in the last decade, including three-dimensional (3D) biomimetic scaffold-free cultures, organ-on-chip microfluidics chips, and 3D bioprinting platforms, which allow for the investigation on patient-specific treatments. The emerging method of 3D bioprinting technology has introduced a time- and cost-efficient approach to create in vitro models that possess the structural and functional characteristics of human organs and tissues by spatially positioning cells and bioink. Here, we review emerging 3D bioprinted models developed for recapitulating the brain environment and glioma tumors, with the purpose of probing glioma cell invasion and gliomagenesis and discuss the potential use of 4D printing and machine learning applications in glioma modelling.Publication Open Access 3D-printed microneedles in biomedical applications(Elsevier, 2021) Rahbarghazi, Reza; Yetişen, Ali Kemal; N/A; Department of Mechanical Engineering; Dabbagh, Sajjad Rahmani; Sarabi, Misagh Rezapour; Sokullu, Emel; Taşoğlu, Savaş; Faculty Member; Faculty Member; Department of Mechanical Engineering; KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Social Sciences and Humanities; Graduate School of Sciences and Engineering; School of Medicine; College of Engineering; N/A; N/A; 163024; 291971Conventional needle technologies can be advanced with emerging nano- and micro-fabrication methods to fabricate microneedles. Nano-/micro-fabricated microneedles seek to mitigate penetration pain and tissue damage, as well as providing accurately controlled robust channels for administrating bioagents and collecting body fluids. Here, design and 3D printing strategies of microneedles are discussed with emerging applications in biomedical devices and healthcare technologies. 3D printing offers customization, cost-efficiency, a rapid turnaround time between design iterations, and enhanced accessibility. Increasing the printing resolution, the accuracy of the features, and the accessibility of low-cost raw printing materials have empowered 3D printing to be utilized for the fabrication of microneedle platforms. The development of 3D-printed microneedles has enabled the evolution of pain-free controlled release drug delivery systems, devices for extracting fluids from the cutaneous tissue, biosignal acquisition, and point-of-care diagnostic devices in personalized medicine.Publication Metadata only A computational biomechanical investigation of posterior dynamic instrumentation: combination of dynamic rod and hinged (dynamic) screw(Asme, 2014) Kiapour, Ali; Goel, Vijay K.; N/A; N/A; Erbulut, Deniz Ufuk; Öktenoğlu, Bekir Tunç; Özer, Ali Fahir; Researcher; Faculty Member; School of Medicine, College of Engineering; School of Medicine; 37661; 220898; 1022Currently, rigid fixation systems are the gold standard for degenerative disk disease treatment. Dynamic fixation systems have been proposed as alternatives for the treatment of a variety of spinal disorders. These systems address the main drawbacks of traditional rigid fixation systems, such as adjacent segment degeneration and instrumentation failure. Pedicle-screw-based dynamic stabilization (PDS) is one type of these alternative systems. The aim of this study was to simulate the biomechanical effect of a novel posterior dynamic stabilization system, which is comprised of dynamic (hinged) screws interconnected with a coiled, spring-based dynamic rod (DSDR), and compare it to semirigid (DSRR and RSRR) and rigid stabilization (RSRR) systems. A validated finite element (FE) model of L1-S1 was used to quantify the biomechanical parameters of the spine, such as range of motion, intradiskal pressure, stresses and facet loads after single-level instrumentation with different posterior stabilization systems. The results obtained from in vitro experimental intact and instrumented spines were used to validate the FE model, and the validated model was then used to compare the biomechanical effects of different fixation and stabilization constructs with intact under a hybrid loading protocol. The segmental motion at L4-L5 increased by 9.5% and 16.3% in flexion and left rotation, respectively, in DSDR with respect to the intact spine, whereas it was reduced by 6.4% and 10.9% in extension and left-bending loads, respectively. After instrumentation-induced intradiskal pressure at adjacent segments, L3-L4 and L5-S1 became less than the intact in dynamic rod constructs (DSDR and RSDR) except in the RSDR model in extension where the motion was higher than intact by 9.7% at L3-L4 and 11.3% at L5-S1. The facet loads were insignificant, not exceeding 12N in any of the instrumented cases in flexion. In extension, the facet load in DSDR case was similar to that in intact spine. The dynamic rod constructions (DSDR and RSDR) led to a lesser peak stress at screws compared with rigid rod constructions (DSRR and RSRR) in all loading cases. A dynamic construct consisting of a dynamic rod and a dynamic screw did protect the adjacent level from excessive motion.Publication Metadata only A new concept of motion preservation surgery of the cervical spine: PEEK rods for the posterior cervical region(Ios Press, 2020) Erbulut, Deniz Ufuk; N/A; Aydın, Ahmet Levent; Sasani, Mehdi; Öktenoğlu, Bekir Tunç; Özer, Ali Fahir; Doctor; Faculty Member; Faculty Member; Faculty Member; N/A; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; N/A; 219451; 220898; 1022Background: Laminectomy may cause kyphotic postoperative deformity in the cervical region leading to segmental instability over time. Laminoplasty may be an alternative procedure to laminectomy, as it protects the spine against post-laminectomy kyphosis; however, similar to laminectomy, laminoplasty may cause sagittal plane deformities by destructing or weakening the dorsal tension band. Objective: Using finite element analysis (FE), we attempted to determine whether a posterior motion preservation system (PEEK posterior rod system concept) could overcome the postoperative complications of laminectomy and laminoplasty and eliminate the side effects of rigid posterior stabilization in the cervical region. Methods: We compared PEEK rods in four different diameters with a titanium rod for posterior cervical fixation. The present study may lead to motion preservation systems of the cervical vertebra. RESULTS: When PEEK rod is compared with titanium rod, considerable increase in range of motion is observed. Conclusions: PEEK rod-lateral mass screw instrumentation systems may be useful in motion preservation surgery of the posterior cervical region.Publication Metadata only A review of bioresorbable implantable medical devices: materials, fabrication, and implementation(Wiley, 2020) N/A; N/A; Department of Mechanical Engineering; Department of Mechanical Engineering; Singh, Rahul; Bathaei, Mohammad Javad; İstif, Emin; Beker, Levent; PhD Student; PhD Student; Researcher; Faculty Member; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; N/A; 354990; 308798Implantable medical devices (IMDs) are designed to sense specific parameters or stimulate organs and have been actively used for treatment and diagnosis of various diseases. IMDs are used for long-term disease screening or treatments and cannot be considered for short-term applications since patients need to go through a surgery for retrieval of the IMD. Advances in bioresorbable materials has led to the development of transient IMDs that can be resorbed by bodily fluids and disappear after a certain period. These devices are designed to be implanted in the adjacent of the targeted tissue for predetermined times with the aim of measurement of pressure, strain, or temperature, while the bioelectronic devices stimulate certain tissues. They enable opportunities for monitoring and treatment of acute diseases. To realize such transient and miniaturized devices, researchers utilize a variety of materials, novel fabrication methods, and device design strategies. This review discusses potential bioresorbable materials for each component in an IMD followed by programmable degradation and safety standards. Then, common fabrication methods for bioresorbable materials are introduced, along with challenges. The final section provides representative examples of bioresorbable IMDs for various applications with an emphasis on materials, device functionality, and fabrication methods.Publication Metadata only A robotic indenter for minimally invasive measurement and characterization of soft tissue response(Elsevier, 2007) Avtan, Levent; Düzgün, Oktay; N/A; N/A; Department of Mechanical Engineering; Samur, Evren; Sedef, Mert; Başdoğan, Çağatay; Master Student; Master Student; Faculty Member; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering College of Engineering; 192890; N/A; 125489The lack of experimental data in current literature on material properties of soft tissues in living condition has been a significant obstacle in the development of realistic soft tissue models for virtual reality based surgical simulators used in medical training. A robotic indenter was developed for minimally invasive measurement of soft tissue properties in abdominal region during a laparoscopic surgery. Using the robotic indenter, force versus displacement and force versus time responses of pig liver under static and dynamic loading conditions were successfully measured to characterize its material properties in three consecutive steps. First, the effective elastic modulus of pig liver was estimated as 10-15 kPa from the force versus displacement data of static indentations based on the small deformation assumption. Then, the stress relaxation function, relating the variation of stress with respect to time, was determined from the force versus time response data via curve fitting. Finally, an inverse finite element solution was developed using ANSYS finite element package to estimate the optimum values of viscoelastic and nonlinear hyperelastic material properties of pig liver through iterations. The initial estimates of the material properties for the iterations were extracted from the experimental data for faster convergence of the solutions.Publication Metadata only A sparse representation strategy to eliminate pseudo-HFO events from intracranial EEG for seizure onset zone localization(Institute of Physics (IOP) Publishing, 2022) Besheli, Behrang Fazli; Sha, Zhiyi; Gavvala, Jay R.; Quach, Michael M.; Curry, Daniel J.; Sheth, Sameer A.; Francis, David J.; Henry, Thomas R.; Ince, Nuri F.; N/A; Karamürsel, Sacit; Gürses, Rabia Candan; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 19597; 110149Objective. High-frequency oscillations (HFOs) are considered a biomarker of the epileptogenic zone in intracranial EEG recordings. However, automated HFO detectors confound true oscillations with spurious events caused by the presence of artifacts. Approach. We hypothesized that, unlike pseudo-HFOs with sharp transients or arbitrary shapes, real HFOs have a signal characteristic that can be represented using a small number of oscillatory bases. Based on this hypothesis using a sparse representation framework, this study introduces a new classification approach to distinguish true HFOs from the pseudo-events that mislead seizure onset zone (SOZ) localization. Moreover, we further classified the HFOs into ripples and fast ripples by introducing an adaptive reconstruction scheme using sparse representation. By visualizing the raw waveforms and time-frequency representation of events recorded from 16 patients, three experts labeled 6400 candidate events that passed an initial amplitude-threshold-based HFO detector. We formed a redundant analytical multiscale dictionary built from smooth oscillatory Gabor atoms and represented each event with orthogonal matching pursuit by using a small number of dictionary elements. We used the approximation error and residual signal at each iteration to extract features that can distinguish the HFOs from any type of artifact regardless of their corresponding source. We validated our model on sixteen subjects with thirty minutes of continuous interictal intracranial EEG recording from each. Main results. We showed that the accuracy of SOZ detection after applying our method was significantly improved. In particular, we achieved a 96.65% classification accuracy in labeled events and a 17.57% improvement in SOZ detection on continuous data. Our sparse representation framework can also distinguish between ripples and fast ripples. Significance. We show that by using a sparse representation approach we can remove the pseudo-HFOs from the pool of events and improve the reliability of detected HFOs in large data sets and minimize manual artifact elimination.Publication Metadata only A virtual reality toolkit for path planning and manipulation at nano-scale(IEEE Computer Soc, 2006) N/A; N/A; Department of Mechanical Engineering; Varol, Aydın; Günev, İhsan; Başdoğan, Çağatay; Master Student; Master Student; Faculty Member; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 125489A virtual reality (VR) toolkit that integrates the human operator into a virtual environment by means of visual and haptic feedback has been developed to design and test manipulation strategies at nano-scale. Currently, the toolkit is capable of modeling the mechanistic interactions between an AFM tip and spherical particles on a substrate surface and generating optimum manipulation paths using a potential field approach. In addition, haptic fixtures were designed to guide the user to follow the calculated paths.Publication Metadata only Adaptive tracking algorithm for trajectory analysis of cells and layer-by-layer assessment of motility dynamics(Pergamon-Elsevier Science Ltd, 2022) Bayraktar, Halil; N/A; Department of Molecular Biology and Genetics; Qureshi, Mohammad Haroon; PhD Student; Faculty Member; Department of Molecular Biology and Genetics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; Graduate School of Sciences and Engineering; College of Sciences; N/A; 105301Tracking biological objects such as cells or subcellular components imaged with time-lapse microscopy enables us to understand the molecular principles about the dynamics of cell behaviors. However, automatic object detection, segmentation and extracting trajectories remain as a rate-limiting step due to intrinsic challenges of video processing. This paper presents an adaptive tracking algorithm (Adtari) that automatically finds the op-timum search radius and cell linkages to determine trajectories in consecutive frames. A critical assumption in most tracking studies is that displacement remains unchanged throughout the movie and cells in a few frames are usually analyzed to determine its magnitude. Tracking errors and inaccurate association of cells may occur if the user does not correctly evaluate the value or prior knowledge is not present on cell movement. The key novelty of our method is that minimum intercellular distance and maximum displacement of cells between frames are dynamically computed and used to determine the threshold distance. Since the space between cells is highly variable in a given frame, our software recursively alters the magnitude to determine all plausible matches in the trajectory analysis. Our method therefore eliminates a major preprocessing step where a constant distance was used to determine the neighbor cells in tracking methods. Cells having multiple overlaps and splitting events were further evaluated by using the shape attributes including perimeter, area, ellipticity and distance. The features were applied to determine the closest matches by minimizing the difference in their magnitudes. Finally, reporting section of our software were used to generate instant maps by overlaying cell features and trajectories. Adtari was validated by using videos with variable signal-to-noise, contrast ratio and cell density. We compared the adaptive tracking with constant distance and other methods to evaluate performance and its efficiency. Our algorithm yields reduced mismatch ratio, increased ratio of whole cell track, higher frame tracking efficiency and allows layer-by-layer assessment of motility to characterize single-cells. Adaptive tracking provides a reliable, accurate, time efficient and user-friendly open source software that is well suited for analysis of 2D fluorescence microscopy video datasets.Publication Metadata only An exploration of plastic deformation dependence of cell viability and adhesion in metallic implant materials(Elsevier, 2016) Gerstein, G.; Maier, H. J.; N/A; N/A; N/A; N/A; Department of Mechanical Engineering; Uzer, Benay; Toker, Sıdıka Mine; Cingöz, Ahmet; Önder, Tuğba Bağcı; Canadinç, Demircan; Researcher; PhD Student; Researcher; Faculty Member; Faculty Member; Department of Mechanical Engineering; N/A; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; School of Medicine; College of Engineering; N/A; 255504; N/A; 184359; 23433The relationship between cell viability and adhesion behavior, and micro-deformation mechanisms was investigated on austenitic 316L stainless steel samples, which were subjected to different amounts of plastic strains (5%, 15%, 25%, 35% and 60%) to promote a variety in the slip and twin activities in the microstructure. Confocal laser scanning microscopy (CLSM) and field emission scanning electron microscopy (FESEM) revealed that cells most favored the samples with the largest plastic deformation, such that they spread more and formed significant filopodial extensions. Specifically, brain tumor cells seeded on the 35% deformed samples exhibited the best adhesion performance, where a significant slip activity was prevalent, accompanied by considerable slip-twin interactions. Furthermore, maximum viability was exhibited by the cells seeded on the 60% deformed samples, which were particularly designed in a specific geometry that could endure greater strain values. Overall, the current findings open a new venue for the production of metallic implants with enhanced biocompatibility, such that the adhesion and viability of the cells surrounding an implant can be optimized by tailoring the surface relief of the material, which is dictated by the micro-deformation mechanism activities facilitated by plastic deformation imposed by machining.