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Publication Metadata only 3D printed biodegradable polyurethaneurea elastomer recapitulates skeletal muscle structure and function(American Chemical Society (ACS), 2021) Gokyer, Seyda; Berber, Emine; Vrana, Engin; Orhan, Kaan; Abou Monsef, Yanad; Guvener, Orcun; Zinnuroglu, Murat; Oto, Cagdas; Huri, Pinar Yilgor; Department of Chemistry; Department of Chemistry; Yılgör, Emel; Yılgör, İskender; Researcher; Faculty Member; Department of Chemistry; College of Sciences; College of Sciences; N/A; 24181Effective skeletal muscle tissue engineering relies on control over the scaffold architecture for providing muscle cells with the required directionality, together with a mechanical property match with the surrounding tissue. Although recent advances in 3D printing fulfill the first requirement, the available synthetic polymers either are too rigid or show unfavorable surface and degradation profiles for the latter. In addition, natural polymers that are generally used as hydrogels lack the required mechanical stability to withstand the forces exerted during muscle contraction. Therefore, one of the most important challenges in the 3D printing of soft and elastic tissues such as skeletal muscle is the limitation of the availability of elastic, durable, and biodegradable biomaterials. Herein, we have synthesized novel, biocompatible and biodegradable, elastomeric, segmented polyurethane and polyurethaneurea (TPU) copolymers which are amenable for 3D printing and show high elasticity, low modulus, controlled biodegradability, and improved wettability, compared to conventional polycaprolactone (PCL) and PCL-based TPUs. The degradation profile of the 3D printed TPU scaffold was in line with the potential tissue integration and scaffold replacement process. Even though TPU attracts macrophages in 2D configuration, its 3D printed form showed limited activated macrophage adhesion and induced muscle-like structure formation by C2C12 mouse myoblasts in vitro, while resulting in a significant increase in muscle regeneration in vivo in a tibialis anterior defect in a rat model. Effective muscle regeneration was confirmed with immunohistochemical assessment as well as evaluation of electrical activity produced by regenerated muscle by EMG analysis and its force generation via a custom-made force transducer. Micro-CT evaluation also revealed production of more muscle-like structures in the case of implantation of cell-laden 3D printed scaffolds. These results demonstrate that matching the tissue properties for a given application via use of tailor-made polymers can substantially contribute to the regenerative outcomes of 3D printed tissue engineering scaffolds.Publication Open Access 3D printed personalized magnetic micromachines from patient blood-derived biomaterials(American Association for the Advancement of Science (AAAS), 2021) Ceylan, Hakan; Doğan, Nihal Olcay; Yaşa, İmmihan Ceren; Department of Mechanical Engineering; Sitti, Metin; Musaoğlu, Miraç Nur; Kulalı, Zeynep Umut; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104; N/A; N/AWhile recent wireless micromachines have shown increasing potential for medical use, their potential safety risks concerning biocompatibility need to be mitigated. They are typically constructed from materials that are not intrinsically compatible with physiological environments. Here, we propose a personalized approach by using patient blood-derivable biomaterials as the main construction fabric of wireless medical micromachines to alleviate safety risks from biocompatibility. We demonstrate 3D printed multiresponsive microswimmers and microrollers made from magnetic nanocomposites of blood plasma, serum albumin protein, and platelet lysate. These micro-machines respond to time-variant magnetic fields for torque-driven steerable motion and exhibit multiple cycles of pH-responsive two-way shape memory behavior for controlled cargo delivery and release applications. Their proteinaceous fabrics enable enzymatic degradability with proteinases, thereby lowering risks of long-term toxicity. The personalized micromachine fabrication strategy we conceptualize here can affect various future medical robots and devices made of autologous biomaterials to improve biocompatibility and smart functionality.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 brief atlas of insulin(Bentham Science, 2022) N/A; Department of Molecular Biology and Genetics; Ayan, Esra; Demirci, Hasan; PhD Student; Faculty Member; Department of Molecular Biology and Genetics; Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); Graduate School of Sciences and Engineering; College of Sciences; N/A; 307350Insulin is an essential factor for mammalian organisms: a regulator of glucose metabolism and other key signaling pathways. Insulin is also a multifunctional hormone whose absence can cause many diseases. Recombinant insulin is widely used in the treatment of diabetes. Understanding insulin, biosimilars, and biobetters from a holistic perspective will help pharmacologically user-friendly molecules design and develop personalized medicine-oriented therapeutic strategies for diabetes. Additionally, it helps to understand the underlying mechanism of other insulin-dependent metabolic disorders. The purpose of this atlas is to review insulin from a biotechnologi-cal, basic science, and clinical perspective, explain nearly all insulin-related disorders and their underlying molecular mechanisms, explore exogenous/recombinant production strategies of patented and research-level insulin/analogs, and highlight their mechanism of action from a structural per-spective. Combined with computational analysis, comparisons of insulin and analogs also provide novel information about the structural dynamics of insulin.Publication Metadata only A case of left testicular artery with high origin passing through a left renal vein fenestration(Via Medica Medical Publishers, 2024) Yılmaz, Ebru; Tatar, Cem; Keskin, Aleyna; Yalçın, Büşra; Gürses, İlke Ali; Graduate School of Health Sciences; School of MedicineBackground: Fenestrations of are extremely rare in the venous system, especially renal veins. This paper aims to present a case of left renal vein fenestration where a high origin testicular artery passes through it. Materials and Methods The variation was observed incidentally in a 74-year-old Caucasian male cadaver during routine retroperitoneal dissections for second year medical students. Results: A fenestration in the mid portion of the left renal vein was observed. The length and height of the fenestration was 23 and 3.6 millimeters, respectively. The left testicular artery passed through the fenestration and followed a normal course distal to the fenestration. Posterior to the left renal vein, the testicular artery originated from the lateral aspect of abdominal aorta, just caudal to the left renal artery. On the right side, the testicular artery had a similar high origin, and two renal arteries were present. No venous variations were observed on the right side. Conclusions: The long course of the left renal vein is a factor of preference for donor kidney selection. Uncommon variations of the left renal veins, such as fenestrations, might result in a change in surgical technique and would put the left donor kidney at risk of prolonged anastomosis time and lower survival rates.Publication Metadata only A chemically inducible organelle rerouting assay to probe primary cilium assembly, maintenance, and disassembly in cultured cells(Humana Press Inc., 2024) Department of Molecular Biology and Genetics; İşsezer, Fatma Başak Turan; Ercan, Muhammed Erdem; Karalar, Elif Nur Fırat; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of SciencesThe primary cilium is a conserved, microtubule-based organelle that protrudes from the surface of most vertebrate cells as well as sensory cells of many organisms. It transduces extracellular chemical and mechanical cues to regulate diverse cellular processes during development and physiology. Loss-of-function studies via RNA interference and CRISPR/Cas9-mediated gene knockouts have been the main tool for elucidating the functions of proteins, protein complexes, and organelles implicated in cilium biology. However, these methods are limited in studying acute spatiotemporal functions of proteins as well as the connection between their cellular positioning and functions. A powerful approach based on inducible recruitment of plus or minus end-directed molecular motors to the protein of interest enables fast and precise control of protein activity in time and in space. In this chapter, we present a chemically inducible heterodimerization method for functional perturbation of centriolar satellites, an emerging membrane-less organelle involved in cilium biogenesis and function. The method we present is based on rerouting of centriolar satellites to the cell center or the periphery in mammalian epithelial cells. We also describe how this method can be applied to study the temporal functions of centriolar satellites during primary cilium assembly, maintenance, and disassembly.Publication Metadata only A clash of civilizations? Examining liberal-democratic values in Turkey and the European Union(Wiley, 2008) Department of Sociology; Dixon, Jeffrey C.; Faculty Member; Department of Sociology; College of Social Sciences and Humanities; N/ATurkey's proposed entry into the European Union (EU) has been undermined by Europeans' perceptions of Turkish-European cultural differences, particularly regarding the liberal-democratic values that the EU promotes (democracy, rule of law, and respect for and appreciation of minority/human rights). Yet, cross-national research on values has not focused on Turkey, the EU, and these liberal-democratic values, leaving assumptions of cultural differences and their explanations untested. Through analyses of World and European Values Survey data (1999-2002), this article asks whether people in Turkey have the same values regarding democracy, rule of law (versus religious and authoritarian rule), and minority/human rights as people in EU member and candidate states (as of 2000)? What factors explain these values? I find that people in Turkey support democracy to the same extent as people in EU member and candidate states, but people in Turkey are more supportive of religious and authoritarian rule and are less tolerant of minorities. Although the 'clash of civilizations' thesis expects liberal values to be ordered according to countries' religious traditions, with western Christian the most supportive and Islamic the least, only for tolerance of minorities values is this pattern found. Instead, economic development most consistently explains differences between Turkey and EU member and candidate states in support for these values. I conclude with calls for theoretical refinement, particularly of the clash of civilizations thesis, along with suggestions for future research to examine more Muslim and Orthodox countries; I discuss the debate over Turkey's EU entry.Publication Metadata only A comparative meta-analysis of peripheral 8-hydroxy-2'-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) levels across mood episodes in bipolar disorder(Elsevier Ltd, 2023) Çeli̇k, H. E. A.; Tuna, G.; Küçükgöncü, S.; N/A; Ceylan, Deniz; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 137755Objective: Oxidative DNA damage has been associated with the pathophysiology of bipolar disorder (BD) as one of the common pathways between increased medical comorbidity and premature aging in BD. Previous evidence shows increased levels of oxidatively induced DNA damage markers, 8-hydroxy-2′-deoxyguanosine (8-OHdG) or its tautomer 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), in patients with BD in comparison to healthy individuals. With the current research, we aim to analyze data on peripheral (blood or urine) 8-OHdG/8-oxo-dG levels across mood states of BD using a meta-analytical approach. Method: A literature search was conducted using the databases PubMed, Scopus, and Web of Science to identify eligible studies (January 1989 to July 2022). Relevant studies were systematically reviewed; a random-effects meta-analysis and a meta-regression analysis were conducted. Results: The current meta-analysis included 12 studies consisting of 808 BD patients (390 in euthymia, 156 in mania, 137 in depression, 16 in mixed episode, 109 not specified) and 563 healthy controls. BD patients that were currently depressed had significantly higher levels of 8-OHdG/8-oxo-dG than healthy controls, while euthymic or manic patients did not differ from healthy controls. A meta-regression analysis showed sex distribution (being female) and older age to be significantly related to increased 8-OHdG/8-oxo-dG levels. Conclusion: Our findings suggest that 8-OHdG/8-oxo-dG may be a state-related marker of depression in BD and may be affected by older age and female gender.Publication Metadata only A knotless labro-bicipital repair technique for SLAP lesions(Elsevier Science Bv, 2015) Koyuncu, Özgür; Uludağ, Serkan; N/A; Eren, İlker; Seyahi, Aksel; Demirhan, Mehmet; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 168021; 52082; 9882Fixation methods for SLAP lesions are still controversial, and the strength of the fixation, suture and knot irritation, and placement and number of anchors are still being discussed. This uncertainty is directly related to the function and anatomy of the superior labrum and attached biceps. Knotless fixation methods close to the biceps anchorage at the 12-o'clock position are favored in recent literature. We describe a practical SLAP repair technique, with a mattress configuration through the biceps anchorage, using a single knotless anchor. Fixing the biceps attachment instead of the labrum alone, in proximity to the biceps, without sutures or knots left in contact with the other intra-articular structures is the superiority of the described technique.Publication Open Access A missed Behçet’s case presenting with spontaneous epidural hematoma(Aves, 2015) Karataş, Levent; Mengi, Gönen; N/A; Taşkıran, Özden Özyemişçi; Faculty Member; School of Medicine; 133091Spinal vascular events related to Behçet's disease are relatively uncommon. Deep vein thrombosis is the most frequent vascular involvement. Anticoagulant therapy is a debated issue in Behçet's disease. In this case report, we present a patient with a delayed diagnosis of Behçet's disease after development of cervical epidural hematoma following anticoagulant therapy due to deep venous thrombosis. Anticoagulant therapy without immunosuppressive therapy leading to uncontrolled systemic inflammation may be the cause of spinal epidural hematoma. On the other hand, epidural vascular involvement as a vasculitic manifestation of Behçet's disease in conjunction with anticoagulant therapy may have predisposed to spontaneous bleeding via increased fragility or microaneurysms in epidural arteries. In this case report, the importance of a multidisciplinary approach to Behçet's disease is emphasized.