Browsing by Subject "extracellular matrix"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Biomechanics of common carotid arteries from mice heterozygous for mgR, the most common mouse model of Marfan syndrome(2009-05-15) Taucer, Anne IreneMarfan syndrome, affecting approximately one out of every 5,000 people, is characterized by abnormal bone growth, ectopia lentis, and often-fatal aortic dilation and dissection. The root cause is a faulty extracellular matrix protein, fibrillin-1, which associates with elastin in many tissues. Common carotids from wild-type controls and mice heterozygous for the mgR mutation, the most commonly used mouse model of Marfan syndrome, were studied in a biaxial testing device. Mechanical data in the form of pressure-diameter and force-stretch tests in both the active and passive states were collected, as well data on the functional responses to phenylephrine, carbamylcholine chloride, and sodium nitroprusside. Although little significant difference was found between the heterozygous and wild-type groups in general, the in vivo stretch for both groups was significantly different from previously studied mouse vessels. Although the two groups do not exhibit significant differences, this study comprises a control group for future work with mice homozygous for mgR, which do exhibit Marfan-like symptoms. As treatment of Marfan syndrome improves, more Marfan patients will survive and age, increasing the likelihood that they will develop many of the vascular complications affecting the normal population, including hypertension and atherosclerosis. Therefore, it is imperative to gather biomechanical data from the Marfan vasculature so that clinicians may predict the effects of vascular complications in Marfan patients and develop appropriate methods of treatment.Item Integrated biomechanical model of cells embedded in extracellular matrix(2009-05-15) Muddana, Hari ShankarNature encourages diversity in life forms (morphologies). The study of morphogenesis deals with understanding those processes that arise during the embryonic development of an organism. These processes control the organized spatial distribution of cells, which in turn gives rise to the characteristic form for the organism. Morphogenesis is a multi-scale modeling problem that can be studied at the molecular, cellular, and tissue levels. Here, we study the problem of morphogenesis at the cellular level by introducing an integrated biomechanical model of cells embedded in the extracellular matrix. The fundamental aspects of mechanobiology essential for studying morphogenesis at the cellular level are the cytoskeleton, extracellular matrix (ECM), and cell adhesion. Cells are modeled using tensegrity architecture. Our simulations demonstrate cellular events, such as differentiation, migration, and division using an extended tensegrity architecture that supports dynamic polymerization of the micro-filaments of the cell. Thus, our simulations add further support to the cellular tensegrity model. Viscoelastic behavior of extracellular matrix is modeled by extending one-dimensional mechanical models (by Maxwell and by Voigt) to three dimensions using finite element methods. The cell adhesion is modeled as a general Velcro-type model. We integrated the mechanics and dynamics of cell, ECM, and cell adhesion with a geometric model to create an integrated biomechanical model. In addition, the thesis discusses various computational issues, including generating the finite element mesh, mesh refinement, re-meshing, and solution mapping. As is known from a molecular level perspective, the genetic regulatory network of the organism controls this spatial distribution of cells along with some environmental factors modulating the process. The integrated biomechanical model presented here, besides generating interesting morphologies, can serve as a mesoscopic-scale platform upon which future work can correlate with the underlying genetic network.Item Study of Cell Material Interactions for Vascular Tissue Engineering Application(2012-07-16) Qu, XinIn the US alone, more than 500,000 coronary artery bypass procedures are performed annually. Tissue engineering shows the potential to construct functional grafts to overcome the limited availability of autologous saphenous veins, relatively poor elasticity and low compliance of synthetic materials (mainly Dacron and polytetrafluoroethylene). In order to meet the low modulus associate with myocyte differentiation, the high suture retention and an ultimate tensile strength (UTS) sufficient to withstand implantation and peak physiological stresses, we designed and characterized a multi-component scaffold comprised of polyurethane electrospun mesh layers bonded together by a fibrin hydrogel matrix. We have demonstrated this composite construct retains the high tensile strength and suture retention strength but displays a "J-shaped" mechanical response similar to that of native coronary artery. To improve our design, poly(ethylene glycol) diacrylate based hydrogel system was utilized as a blank slate to study the phenotypic regulation by cell material interactions. Fibrinogen, fibronectin, laminin and collagen type IV were incorporated into the hydrogel to mimic the stimuli from extracellular matrix (ECM) proteins. Surprisingly, no significant effect was detected on induction of smooth muscle cell (SMC) differentiation marker expression, activation of mitogen-activated protein (MAP) kinases pathway, or alteration of surface integrin expression profile. However, fibronectin showed repression of undesired phenotypes in SMC differentiation. In contrast to ECM proteins, glycosaminoglycans (GAGs) showed more influence on regulating SMC phenotype. By using a scaffold environment intended to be mimetic of early atherosclerosis, the impact of GAG identity on SMC foam cell formation was explored. We focused on chondroitin sulfate C (CSC), dermatan sulfate (DS), and an intermediate molecular weight hyaluronan (HA_IMW, ~400 kDa), the levels and/or distribution of which are significantly altered in atherosclerosis. CSC and DS hydrogels were associated with greater SMC phagocytosis of apolipoprotein B than HA_IMW gels. However, only SMCs in DS constructs maintained increased expression of adipocyte marker A-FABP relative to HA_IMW gels over 35 days of culture. Combined, our results suggested interesting roles for fibronectin and HA_IMW in repression of undesired phenotypes in SMC differentiation, which could give insights into rational design of novel biomaterials for vascular tissue engineering applications.