Research Project:
Yeni nesil kalp-damar cihazları için süper kan hücreleri, çok fazlı hücre akışının kontrolü ve ileri ggörüntüleme

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TB.00580

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Pekkan, Kerem
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PublicationOpen Access
Evaluation of the total hydrodynamic energy loss using 4D flow MRI in a case with Fontan failure
(Elsevier, 2024) Gümüş, Terman; Ödemiş, Ender; Özkök, Serçin; Pekkan, Kerem; Aka, İbrahim Başar; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; KUH (Koç University Hospital); School of Medicine; Yes; College of Engineering; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING; KUH (KOÇ UNIVERSITY HOSPITAL); SCHOOL OF MEDICINE
Fontan Failure (FF) is a common problem for single-ventricle patients as they reach adulthood. Although several mechanisms may cause FF, an optimized blood flow stream through the surgical conduits is essential to avoid excessive energy loss (EL). Recent clinical studies showed EL is related to the quality of life, exercise capacity, and hepatic function since the single-ventricle feeds pulmonary and systemic circulation serially. 4D flow MRI effectively estimates EL in Fontan circulation and allows clinicians to compare the effectiveness of the treatment strategy concerning pre-intervention. Here, we present 26-year-old women with FF who had normal cardiac catheterization findings and were treated according to high EL definitions that are measured through 4D flow MRI. © 2024
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Interstitial flow, pressure and residual stress in the aging carotid artery model in FEBio
(Springer, 2023) Pekkan, Kerem; Lashkarinia, Seyedeh Samaneh; Altundemir, Sercan; Uguz, A. Kerem; Department of Mechanical Engineering; Yes; College of Engineering
Vascular smooth muscle cells (VSMCs) are subject to interstitial flow-induced shear stress, which is a critical parameter in cardiovascular disease progression. Transmural pressure loading and residual stresses alter the hydraulic conductivity of the arterial layers and modulate the interstitial fluid flux through the arterial wall. In this paper, a biphasic multilayer model of a common carotid artery (CCA) with anisotropic fiber-reinforced soft tissue and strain-dependent permeability is developed in FEBio software. After the verification of the numerical predictions, age-related arterial thickening and stiffening effects on arterial deformation and interstitial flow are computed under physiological geometry and physical parameters. We found that circumferential residual stress shifts outward in each layer and its gradient increases up to 6 times with aging. Internally pressurized CCA displays nonlinear deformation. In the aged artery, the circumferential stress becomes greater on the media layer (82-158 kPa) and lower on the intima and adventitia (19-23 kPa and 25-28 kPa, respectively). The radial compression of the intima reduces the total hydraulic conductivity by 48% in the young and 16% in the aged arterial walls. Consequently, the average radial interstitial flux increases with pressure by 14% in the young and 91% in the aged arteries. Accordingly, the flow shear stress experienced by the VSMCs becomes more significant for aged arteries, which may accelerate cardiovascular disease progression compared to young arteries.
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PublicationOpen Access
Modulation of mechanosensitive genes during embryonic aortic arch development
(WILEY, 2024) Çoban, Merve Nur; Köse, Tansu Gölcez; Pekkan, Kerem; Sevgin, Börteçine; Siddiqui, Hummaira Banu; Golcez, Tansu; Celik, Merve; Suder, Ilke; Ozoren, Nesrin; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; Yes; College of Engineering; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
BackgroundEarly embryonic aortic arches (AA) are a dynamic vascular structures that are in the process of shaping into the great arteries of cardiovascular system. Previously, a time-lapsed mechanosensitive gene expression map was established for AA subject to altered mechanical loads in the avian embryo. To validate this map, we investigated effects on vascular microstructure and material properties following the perturbation of key genes using an in-house microvascular gene knockdown system.ResultsAll siRNA vectors show a decrease in the expression intensity of desired genes with no significant differences between vectors. In TGF beta 3 knockdowns, we found a reduction in expression intensities of TGF beta 3 (<= 76%) and its downstream targets such as ELN (<= 99.6%), Fbn1 (<= 60%), COL1 (<= 52%) and COL3 (<= 86%) and an increase of diameter in the left AA (23%). MMP2 knockdown also reduced expression levels in MMP2 (<= 30%) and a 6-fold increase in its downstream target COL3 with a decrease in stiffness of the AA wall and an increase in the diameter of the AA (55%). These in vivo measurements were confirmed using immunohistochemistry, western blotting and a computational growth model of the vascular extracellular matrix (ECM).ConclusionsLocalized spatial genetic modification of the aortic arch region governs the vascular phenotype and ECM composition of the embryo and can be integrated with mechanically-induced congenital heart disease models.

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