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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 Open Access Biophotonic sensor applications based on photonic atoms - art. no. 60990Q(Society of Photo-optical Instrumentation Engineers (SPIE), 2006) Demir, Abdullah; Department of Physics; Serpengüzel, Ali; Faculty Member; Department of Physics; College of Sciences; 27855Microsphere resonators, i.e., photonic atoms, have found wide area of application in optical spectroscopy, quantum optics, cavity QED, switching, and sensing. Photonic atoms have unique optical properties such as high quality factor (Q-factor) morphology dependent resonances (MDR's), and relatively small volumes. High-Q MDR's are very sensitive to the refractive index change and microsphere uniformity. These tiny optical cavities, whose diameters vary from a few to several hundred micrometers, have resonances with reported Q-factors as large as 3x10(9). Due to their sensitivity, MDR's are also considered for biosensor applications. Binding of a protein or other biomolecules can be monitored by observing the wavelength shift of MDR's. A biosensor, based on this optical phenomenon, can even detect a single molecule, depending on the quality of the system. In this work, elastic scattering spectra from photonic atoms of different materials are experimentally obtained and MDR'S are observed. Preliminary results of unspecific binding of biomolecules are presented. Elastic light scattering spectra of MDR's for biosensor applications are calculated numerically for biomolecules such as Bovine Serum Albumin (BSA) and for Deoxyribo Nucleic Acid (DNA).Publication Open Access Haemodynamic recovery properties of the torsioned testicular Artery Lumen(Nature Publishing Group (NPG), 2017) Göktaş, Selda; Pişkin, Şenol; Çapraz, Can T.; Çakmak, Yusuf O.; N/A; Department of Mechanical Engineering; Yalçın, Özlem; Ermek, Erhan; Pekkan, Kerem; Other; Faculty Member; Department of Mechanical Engineering; School of Medicine; College of Engineering; 218440; 109991; 161845Testicular artery torsion (twisting) is one such severe vascular condition that leads spermatic cord injury. In this study, we investigate the recovery response of a torsioned ram testicular artery in an isolated organ-culture flow loop with clinically relevant twisting modes (90°, 180°, 270° and 360° angles). Quantitative optical coherence tomography technique was employed to track changes in the lumen diameter, wall thickness and the three-dimensional shape of the vessel in the physiological pressure range (10–50 mmHg). As a control, pressure-flow characteristics of the untwisted arteries were studied when subjected to augmented blood flow conditions with physiological flow rates up to 36 ml/min. Both twist and C-shaped buckling modes were observed. Acute increase in pressure levels opened the narrowed lumen of the twisted arteries noninvasively at all twist angles (at ∼22 mmHg and ∼35 mmHg for 360°-twisted vessels during static and dynamic flow experiments, respectively). The association between the twist-opening flow rate and the vessel diameter was greatly influenced by the initial twist angle. The biomechanical characteristics of the normal (untwisted) and torsioned testicular arteries supported the utilization of blood flow augmentation as an effective therapeutic approach to modulate the vessel lumen and recover organ reperfusion.
Publication Metadata only Heart valve inspired and multi-stream aortic cannula: novel designs for cardiopulmonary bypass improvement in neonates(Wiley, 2019) Department of Mechanical Engineering; Department of Mechanical Engineering; Rasooli, Reza; Pekkan, Kerem; Researcher; Faculty Member; Department of Mechanical Engineering; College of Engineering; College of Engineering; N/A; 161845In a typical open-heart surgery, the blood flow through the aortic cannula is a critical element of the cardiopulmonary bypass (CPB) procedure. Especially for the neonatal and pediatric CPB flow conditions, the need for small hydraulic diameter and large blood flow results confined turbulent jet flow regimes that exacerbate blood damage and platelet activation. Simultaneously, the confined jet wake leads to complex stagnation and recirculating flows that cause considerable thrombosis, blood, and endothelial cell damage through the aorta. Thus, an ideal neonatal CPB cannula should be able to generate optimal jet expansion so that sufficient cerebral perfusion is achieved through the head-neck vessels to avoid postoperative neurological complications and developmental defects in children. To address these challenges, a formal bio-inspired design framework is conducted to reach the desired cannula function through novel analogous biological components, first-time in literature. Among the biological jet flow regimes studied, the ventricle filling-jet generated through the atrio-ventricle (AV) valves are found to be the most promising. Inspired from human AV valve shapes, 8 different novel cannula designs, considering the size constrains of neonatal and pediatric patients are built via high-accurate micro stereo-lithography. Using 2-dimensional time-resolved particle image velocimetry the turbulent jet wake characteristics are measured and compared. The proposed designs have exhibited a significant improvement as compared to standard circular cannula by around 30% reduction in maximum outflow velocity and more than 80% reduction in potential core length and spatial energy dissipation which results in a lower risk of cardiovascular and blood damage.Publication Metadata only Noninvasive in vivo determination of residual strains and stresses(ASME, 2015) N/A; Department of Molecular Biology and Genetics; Department of Mechanical Engineering; Donmazov, Samir; Pişkin, Şenol; Pekkan, Kerem; PhD Student; Researcher; Faculty Member; Department of Molecular Biology and Genetics; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 148702; 161845Vascular growth and remodeling during embryonic development are associated with blood flow and pressure induced stress distribution, in which residual strains and stresses play a central role. Residual strains are typically measured by performing in vitro tests on the excised vascular tissue. In this paper, we investigated the possibility of estimating residual strains and stresses using physiological pressure-radius data obtained through in vivo noninvasive measurement techniques, such as optical coherence tomography or ultrasound modalities. This analytical approach first tested with in vitro results using experimental data sets for three different arteries such as rabbit carotid artery, rabbit thoracic artery, and human carotid artery based on Fung's pseudostrain energy function and Delfino's exponential strain energy function (SEF). We also examined residual strains and stresses in the human swine iliac artery using the in vivo experimental ultrasound data sets corresponding to the systolic-to-diastolic region only. This allowed computation of the in vivo residual stress information for loading and unloading states separately. Residual strain parameters as well as the material parameters were successfully computed with high accuracy, where the relative errors are introduced in the range of 0-7.5%. Corresponding residual stress distributions demonstrated global errors all in acceptable ranges. A slight discrepancy was observed in the computed reduced axial force. Results of computations performed based on in vivo experimental data obtained from loading and unloading states of the artery exhibited alterations in material properties and residual strain parameters as well. Emerging noninvasive measurement techniques combined with the present analytical approach can be used to estimate residual strains and stresses in vascular tissues as a precursor for growth estimates. This approach is also validated with a finite element model of a general two-layered artery, where the material remodeling states and residual strain generation are investigated.Publication Metadata only Photocrosslinking of styrene-butadiene-styrene (SBS) networks formed by thiol-ene reactions and their influence on cell survival(IOP Publishing Ltd, 2015) Department of Chemical and Biological Engineering; N/A; Department of Chemical and Biological Engineering; Gidon, Doğan; Aydın, Derya; Kızılel, Seda; Researcher; Researcher; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; N/A; College of Engineering; Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); N/A; N/A; 28376Styrene-butadiene-styrene (SBS) triblock copolymer has been conventionally used as synthetic rubber. However, the potential of SBS for biomedical applications has only been considered in limited earlier reports. Here, we demonstrate an effective approach to designing a photocrosslinked SBS network. Rheological analysis has been conducted for the investigation of the storage modulus of the resultant network. Crosslinked SBS networks were synthesized and characterized through optical and electron microscope imaging. The crosslink density of the network, calculated from swelling experiments, was 643 mol m(-3), where higher swelling in a hydrophobic medium was observed compared to the swelling measured in water. Cell survival analysis with HeLa cells and NIH/3T3 fibroblasts revealed that these networks are non-toxic, and that they could be considered for a variety of biomedical applications.Publication Metadata only Spatiotemporal remodeling of embryonic aortic arch: stress distribution, microstructure, and vascular growth in silico(Springer Heidelberg, 2020) N/A; Department of Mechanical Engineering; Department of Mechanical Engineering; Department of Mechanical Engineering; Department of Mechanical Engineering; Department of Mechanical Engineering; Lashkarinia, Seyedeh Samaneh; Çoban, Gürsan; Ermek, Erhan; Çelik, Merve; Pekkan, Kerem; Researcher; Researcher; Other; Undergraduate Student; Faculty Member; Department of Mechanical Engineering; College of Engineering; College of Engineering; College of Engineering; College of Sciences; College of Engineering; N/A; 148688; N/A; N/A; 161845The microstructure formaturevessels has been investigated in detail, while there is limited information about theembryonicstages, in spite of their importance in the prognosis of congenital heart defects. It is hypothesized that the embryonic vasculature represents a disorganized but dynamic soft tissue, which rapidly evolves toward a specialized multi-cellular vascular structure under mechanical loading. Here the microstructural evolution process of the embryonic pharyngeal aortic arch structure was simulated using an in ovo validated long-term growth and remodeling computational model, implemented as an in-house FEBio plug-in. Optical coherence tomography-guided servo-null pressure measurements are assigned as boundary conditions through the critical embryonic stages. The accumulation of key microstructural constituents was recorded through zoom confocal microscopy for all six embryonic arch arteries simultaneously. The total amount and the radial variation slope of the collagen along the arch wall thickness in different arch types and for different embryonic times, with different dimension scales, were normalized and compared statistically. The arch growth model shows that the stress levels around the lumen boundary increase from approximate to 270Pa (Stage 18) to a level higher than approximate to 600Pa (Stage 24), depending on matrix constituent production rates, while the homeostatic strain level is kept constant. The statistical tests show that although the total collagen levels differentiate among bilateral positions of the same arch, the shape coefficient of the matrix microstructural gradient changes with embryonic time, proving radial localization, in accordance with numerical model results. In vivo cell number (DAPI) and vascular endothelial growth factor distributions followed similar trends.Publication Open Access Transition from the fetal to neonatal circulation: Modeling the effects of umbilical cord clamping(Elsevier, 2015) Yiğit, Mehmet B.; Kowalski, William J.; Hutchon, David J.R.; Department of Mechanical Engineering; Pekkan, Kerem; Faculty Member; Department of Mechanical Engineering; College of Engineering; 161845Hemodynamics of the fetal to neonatal transition are orchestrated through complex physiological changes and results in cardiovascular adaptation to the adult biventricular circulation. Clinical practice during this critical period can influence vital organ physiology for normal newborns, premature babies and congenital heart defect patients. Particularly, the timing of the cord clamping procedure, immediate (ICC) vs. delayed cord clamping (DCC), is hypothesized to be an important factor for the transitory fetal hemodynamics. The clinical need for a quantitative understanding of this physiology motivated the development of a lumped parameter model (LPM) of the fetal cardio-respiratory system covering the late-gestation to neonatal period. The LPM was validated with in vivo clinical data and then used to predict the effects of cord clamping procedures on hemodynamics and vital gases. Clinical time-dependent resistance functions to simulate the vascular changes were introduced. For DCC, placental transfusion (31.3ml) increased neonatal blood volume by 11.7%. This increased blood volume is reflected in an increase in preload pressures by ~20% compared to ICC, which in turn increased the cardiac output (CO) by 20% (CO.sub.ICC =993ml/min; CO.sub.DCC =1197ml/min). Our model accurately predicted dynamic flow patterns in vivo. DCC was shown to maintain oxygenation if the onset of pulmonary respiration was delayed or impaired. On the other hand, a significant 25% decrease in oxygen saturations was observed when applying ICC under the same physiological conditions. We conclude that DCC has a significant impact on newborn hemodynamics, mainly because of the improved blood volume and the sustained placental respiration.Publication Metadata only Visible-light-induced synthesis of pH-responsive composite hydrogels for controlled delivery of the anticonvulsant drug pregabalin(Elsevier Sci Ltd, 2015) N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Çevik, Özlem; Gidon, Doğan; Kızılel, Seda; N/A; Undergraduate; Faculty Member; Department of Chemical and Biological Engineering; N/A; College of Engineering; College of Engineering; N/A; N/A; 28376We report here a novel method for the synthesis of a pH-responsive composite using visible light. Formation of the pH-responsive layer is based on poly(methacrylic acid-g-ethylene glycol) as the macromer, eosin Y as the photoinitiator and triethanolamine as the co-initiator. The hydrogel was functionalized with hydrophobic domains through incorporation of crosslinked styrene-butadiene-styrene (SBS) copolymer into the pH-responsive prepolymer. Swelling ratios were decreased with the addition of SBS, and resulted in high hydrogel crosslink density. The composite allowed for controlled release of an anticonvulsant model drug, pregabalin, under neutral pH condition and the release was analyzed to describe the mode of transport through the network. In vitro human fibroblast survival assay and in vivo rabbit implantation experiments demonstrated that this hybrid network is not toxic and has desirable biocompatibility properties. This is the first report about the synthesis of a pH-responsive network incorporating crosslinked SBS synthesized under visible light. The approach for multifunctional membranes could allow the incorporation of molecules with specific functionalities so that sequential molecule delivery in response to specific stimuli could be achieved. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.