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    Publication
    Doxorubicin-loaded liposome-like particles embedded in chitosan/hyaluronic acid-based hydrogels as a controlled drug release model for local treatment of glioblastoma
    (Elsevier B.V., 2024) Adiguzel, Seyfure; Karamese, Miray; Kugu, Senanur; Kacar, Elif Ayse; Esen, Muhammed Fevzi; Erdogan, Hakan; Bacanli, Merve Güdül; Altuntas, Sevde; Department of Mechanical Engineering; Taşoğlu, Savaş; Department of Mechanical Engineering; College of Engineering
    Glioblastoma (GBM) resection and medication treatment are limited, and local drug therapies are required. This study aims to create a hybrid system comprising liposome-like particles (LLP-DOX) encapsulated in chitosan/hyaluronic acid/polyethyleneimine (CHI/HA/PEI) hydrogels, enabling controlled local delivery of doxorubicin (DOX) into the resection cavity for treating GBM. CHI/HA/PEI hydrogels were characterized morphologically, physically, chemically, mechanically, and thermally. Findings revealed a high network and compact micro-network structure, along with enhanced physical and thermal stability compared to CHI/HA hydrogels. Simultaneously, drug release from CHI/HA/PEI/LLP-DOX hydrogels was assessed, revealing continuous and controlled release up to the 148th hour, with no significant burst release. Cell studies showed that CHI/HA/PEI hydrogels are biocompatible with low genotoxicity. Additionally, LLP-DOX-loaded CHI/HA/PEI hydrogels significantly decreased cell viability and gene expression levels compared to LLP-DOX alone. It was also observed that the viability of GBM spheroids decreased over time when interacting with CHI/HA/PEI/LLP-DOX hydrogels, accompanied by a reduction in total surface area and an increase in apoptotic tendencies. In this study, we hypothesized that creating a hybrid drug delivery system by encapsulating DOX-loaded LLPs within a CHI/HA/PEI hydrogel matrix could achieve sustained drug release, improve anticancer efficacy via localized treatment, and effectively mitigate GBM progression for 3D microtissues.
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    Evaluation of the effects of aging on the aorta stiffness in relation with mineral and trace element levels: an optimized method via custom-built stretcher device
    (Springernature, 2021) Turan, Belma; N/A; Department of Mechanical Engineering; N/A; Department of Mechanical Engineering; N/A; Aydemir, Duygu; Salman, Naveed; Karimzadehkhouei, Mehrdad; Alaca, Burhanettin Erdem; Ulusu, Nuriye Nuray; Faculty Member; Other; Researcher; Faculty Member; Faculty Member; Department of Mechanical Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); School of Medicine; College of Engineering; N/A; College of Engineering; School of Medicine; N/A; N/A; N/A; 115108; 6807
    Aortic stiffness represents the major cause of aging and tightly associated with hypertension, atherosclerosis, cardiovascular diseases, and increased mortality. Mechanical characteristics of the aorta play a vital role in the blood flow, circulation, systolic pressure, and aortic stiffness; however, the correlation of trace element and mineral levels with aortic stiffness has not been studied before. Balance in the trace elements and minerals is vital for the biological functions; however, natural aging may alter this balance. Thus, after measuring aortic stiffness of aged and young rat aortas by a custom-built stretcher device, trace element and mineral levels were evaluated via ICP-MS. Also, biomarkers of aging including blood pressure, arterial pressure glucose, insulin levels, and histochemical parameters were investigated as well. Aortic stiffness, blood glucose, plasma insulin, systolic, diastolic, and mean arterial pressure significantly increased by aging in the aorta of aged rats compared with the young ones. Also, Fe, Al, Co, Ni, Zn, Sr, Na, Mg, and K levels increased in the aged aorta samples compared with the young aorta samples of rats. Increased levels of the indicated elements may be correlated with the development and progression of aortic stiffness and vascular complications. Thus, possible mechanisms correlating aortic stiffness with the imbalance in the trace element and mineral levels should be further investigated.
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    The impact of the vitamin D and resveratrol administration on the stiffness and elasticity of T2DM rat aorta associated with the trace element and mineral levels
    (Elsevier Inc., 2024) Anapali-Aykac, Merve; Ulutin, Turgut; Komurcu-Bayrak, Evrim; Kaya-Dagistanli, Fatma; Department of Mechanical Engineering; Ulusu, Nuriye Nuray; Aydemir, Duygu; Salman, Naveed; Karimzadehkhouei, Mehrdad; Alaca, Burhanettin Erdem; Department of Mechanical Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); n2STAR-Koç University Nanofabrication and Nanocharacterization Center for Scientifc and Technological Advanced Research; School of Medicine; Graduate School of Health Sciences; College of Engineering
    Background: Type 2 diabetes mellitus (T2DM) is directly associated with increased aortic stiffness, reduced aortic elasticity, and aortic dissection, which are independent risk factors for cardiovascular death. Since Vit D and resveratrol have been reported due to their cardioprotective effects, in this study, we aim to evaluate the impact of Vit D and resveratrol treatment alone or in combination on the aortic health associated with trace element and mineral levels in a high-fructose diet/streptozotocin-induced T2DM model. Methods: We investigated biomechanical changes of the aorta samples via a custom-built stretcher, where trace element and mineral levels in aorta samples were determined via inductively coupled plasma mass spectrometry (ICP-MS) following acidic microwave digestion. Results: Vitamin D treatment ameliorated the adverse effects of T2DM on aortic stiffness, aortic elasticity, and relaxation modulus in diabetic rats. Trace element and mineral levels correlated with cardiovascular homeostasis, including Fe, Cu, Zn, Se, and Na, have been regulated upon Vit D treatment in diabetic and healthy rats. On the other hand, resveratrol treatment alone or in combination with Vit D did not show any positive effects on biomechanical properties and trace element metabolism of diabetic or healthy rats, according to our data. Conclusion: Vit D can be used in T2DM patients to protect their cardiovascular health and should be considered a promising targeted therapy approach via nanoparticles to target cardiovascular diseases in the future.