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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 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 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.Publication Metadata only Application of the finite element method in spinal implant design and manufacture(Woodhead Publ Ltd, 2012) N/A; Department of Mechanical Engineering; Zafarparandeh, Iman; Lazoğlu, İsmail; PhD Student; Faculty Member; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 179391This chapter reviews the application of the finite element (FE) method in designing and manufacturing spinal implants. The structure of the chapter is built upon the procedure of creating the FE model for the human spine, which consists of establishing the FE model for each component of the spine, including mesh generation and material property, verification, validation and, finally, implant design process. Each part of the spine FE model is discussed from the simulation point of view and available models are introduced. For the implant design, some examples are chosen from the literature, which are also being used widely in the medical industry.Publication Metadata only Electro-conductive silica nanoparticles-incorporated hydrogel based on alginate as a biomimetic scaffold for bone tissue engineering application(Taylor and Francis Ltd., 2023) Derakhshankhah, Hossein; Eskandani, Morteza; Vandghanooni, Somayeh; Jaymand, Mehdi; Department of Mechanical Engineering; N/A; Taşoğlu, Savaş; Nakhjavani, Sattar Akbar; Faculty Member; Researcher; Department of Mechanical Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; N/A; 291971; N/AAn innovative electrically conductive hydrogel was fabricated through the incorporation of silica nanoparticles (SiO2 NPs) and poly(aniline-co-dopamine) (PANI-co-PDA) into oxidized alginate (OAlg) as a biomimetic scaffold for bone tissue engineering application. The developed self-healing chemical hydrogel was characterized by FTIR, SEM, TEM, XRD, and TGA. The electrical conductivity and swelling ratio of the hydrogel were obtained as 1.7 × 10−3 S cm−1 and 130%, respectively. Cytocompatibility and cell proliferation potential of the developed scaffold were approved by MTT assay using MG-63 cells. FE-SEM imaging approved the potential of the fabricated scaffold for hydroxyapatite (HA) formation and bioactivity induction through immersing in SBF solution.Publication Metadata only Evaluation of passive oxide layer formation–biocompatibility relationship in NiTi shape memory alloys: geometry and body location dependency(Elsevier, 2014) Maier, H. J.; N/A; Department of Mechanical Engineering; N/A; Toker, Sıdıka Mine; Canadinç, Demircan; Birer, Özgür; PhD Student; Faculty Member; Researcher; Department of Mechanical Engineering; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; College of Engineering; N/A; 255504; 23433; N/AA systematic set of ex-situ experiments were carried out on Nickel-Titanium (NiTi) shape memory alloy (SMA) in order to identify the dependence of its biocompatibility on sample geometry and body location. NiTi samples with three different geometries were immersed into three different fluids simulating different body parts. The changes observed in alloy surface and chemical content of fluids upon immersion experiments designed for four different time periods were analyzed in terms of ion release, oxide layer formation, and chemical composition of the surface layer. The results indicate that both sample geometry and immersion fluid significantly affect the alloy biocompatibility, as evidenced by the passive oxide layer formation on the alloy surface and ion release from the samples. Upon a 30 day immersion period, all three types of NiTi samples exhibited lower ion release than the critical value for clinic applications. However; a significant amount of ion release was detected in the case of gastric fluid, warranting a thorough investigation prior to utility of NiTi in gastrointestinal treatments involving long-time contact with tissue. Furthermore, certain geometries appear to be safer than the others for each fluid, providing a new set of guidelines to follow while designing implants making use of NiTi SMAs to be employed in treatments targeting specific body parts.Publication Metadata only In silico analysis of modular bone plates(Elsevier, 2021) N/A; N/A; Department of Mechanical Engineering; N/A; Department of Mechanical Engineering; Subaşı, Ömer; Oral, Atacan; Noyan, Sinan; Tunçözgür, Orçun; Lazoğlu, İsmail; PhD Student; PhD Student; Undergraduate Student; Master Student; Faculty Member; Department of Mechanical Engineering; Manufacturing and Automation Research Center (MARC); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; N/A; N/A; 179391Background: Inventory management or immediate availability of fracture plates can be problematic since for each surgical intervention a specific plate of varying size and functionality must be ordered. Modularization of the standard monolithic plate is proposed to address this issue. Methods: The effects of four different unit module design parameters (type, degree of modularization, connector screw diameter, sandwich ratio) on the plate bending stiffness and failure are investigated in a finite element four-point-bending analysis. A chosen, best-performing modular plate is then tested in silico for a simple diaphyseal tibial fracture scenario under anatomical compressional, torsional, and bending loads . Results: A modularization strategy is proposed to match the monolithic plate bending properties as closely as possible. With the best combination of design parameters, a fully modularized equivalent length plate with a 42.3% decrease in stiffness and 46.2% decrease in strength could be assembled. The chosen modular plate also displayed sufficient mechanical performance under the fracture fixation scenarios for a potentially successful osteosynthesis. Conclusions: Via computational methods, the viability of the modularization strategy as an alternate to the traditional monolithic plate is demonstrated. As a further realized advantage, the modular plates can alleviate stress shielding thanks to the reduced stiffness.Publication Metadata only In silico analysis of superelastic nitinol staples for trans-sternal closure(Elsevier, 2020) N/A; N/A; Department of Mechanical Engineering; Subaşı, Ömer; Torabnia, Shams; Lazoğlu, İsmail; PhD Student; PhD Student; Faculty Member; Department of Mechanical Engineering; Manufacturing and Automation Research Center (MARC); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 179391Background: Superelastic Nitinol staples, utilized routinely in foot surgeries, are proposed to be used for sternal closure application in this study. It is hypothesized that the shape memory induced superelasticity will allow multiple staples placed along the sternum to promote fast and safe recovery by maintaining constant clamping pressure at the sternotomy midline. Methods: Two different Nitinol staples of different alloying compositions, one representing the metal formed wire geometry and, the other, powder metallurgy manufactured rectangular geometry, are chosen from the literature. Austenite finish temperatures of both materials are confirmed to be appropriately below the body temperature for superelastic shape memory activation. The adopted finite element superelasticity model is first validated and, via design optimization of parametrized dimensions, the staple geometries for producing maximal clamping forces are identified. The performances of the optimized staples for full trans-sternal closure (seven staples for each) are then tested under lateral sternal loading in separate computational models. Results: The optimized metal formed staple exerts 70.2 N and the optimized powder metallurgy manufactured staple exerts 245 N clamping force, while keeping the maximum localized stresses under the yield threshold for 90 degrees leg bending. Testing the staple-sternum constructs under lateral sternal loading revealed that the former staple can be utilized for small-chested patients with lower expected physiological loading, while the latter staple can be used for high-risk patients, for which high magnitude valsalva maneuver is expected. Conclusion: Computational results prove that superelastic Nitinol staples are promising candidates as alternatives to routinely performed techniques for sternal closure.Publication Metadata only Liposomes under shear: structure, dynamics, and drug delivery applications(Wiley-VCH, 2023) Department of Chemical and Biological Engineering; N/A; Şenses, Erkan; Karaz, Selcan; Faculty Member; Master Student; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; 280298; N/AThe targeted delivery to specific locations while not causing damage to healthy tissues efficiently remains a challenge in drug delivery systems. Through addressing this issue, stimuli-responsive materials have been under investigation. As one of the fundamental forces associated with blood flow, shear stress is taken as an advantage to design shear-sensitive drug carriers. Although blood flow is modeled as laminar flow under normal conditions, in case of constrictions caused by endothelial shear stress, cardiovascular diseases, or angiogenesis due to tumor formation, local shear stress can dramatically increase. To date, shear-sensitive materials have been investigated under two main categories: shear-disaggregated and shear-deformed nanoparticles based on their structural mechanism after exposure to high-shear stress. Among them, liposomes are promising materials with their soft and deformable structure, high biocompatibility, controlled-release properties, and sensitivity to shear stress. Herein, in this review, the effects of shear stress on liposomes in terms of their structural changes, flow regimes, rheological properties, and drug delivery applications are discussed. It is believed that this work provides a basis for designing more effective drug delivery systems considering the complexity of the human body.Publication Metadata only Molecularly imprinted nanoparticles with recognition properties towards diphtheria toxin for elisa applications(Taylor & Francis) Alkanli, Suleyman Serdar; Yasar, Merve; Guven, Celal; Kahraman, M. Vezir; Apohan, Nilhan Kayaman; Aktas, Zerrin; Oncul, Mustafa Oral; Unlu, Ayhan; Akcakaya, Handan; Yöntem, Fulya Dal; Teaching Faculty; School of Medicine; 232576Plastic antibodies can be used for in vitro neutralization of biomacromolecules with different fragments due to their potential in separation, purification, chemical sensor, catalysis and drug production studies. These polymer nanoparticles with binding affinity and selectivity comparable to natural antibodies were prepared using functional monomer synthesis and copolymerization of acrylic monomers via miniemulsion polymerization. As a result, the in vitro cytotoxic effect from diphtheria toxin was reduced by MIPs. In vitro imaging experiments of polymer nanoparticles (plastic antibodies) were performed to examine the interaction of diphtheria toxin with actin filaments, and MIPs inhibited diphtheria toxin damage on actin filaments. The enzyme-linked immunosorbent assay (ELISA) was performed with plastic antibodies labeled with biotin, and it was determined that plastic antibodies could also be used for diagnostic purposes. We report that molecularly imprinted polymers (MIPs), which are biocompatible polymer nanoparticles, can capture and reduce the effect of diphtheria toxic and its fragment A.