Architecture and Composition Dictate Viscoelastic Properties of Organ-Derived Extracellular Matrix Hydrogels

The proteins and polysaccharides of the extracellular matrix (ECM) provide architectural support as well as biochemical and biophysical instruction to cells. Decellularized, ECM hydrogels replicate in vivo functions. The ECM’s elasticity and water retention renders it viscoelastic. In this study, we compared the viscoelastic properties of ECM hydrogels derived from the skin, lung and (cardiac) left ventricle and mathematically modelled these data with a generalized Maxwell model. ECM hydrogels from the skin, lung and cardiac left ventricle (LV) were subjected to a stress relaxation test under uniaxial low-load compression at a 20%/s strain rate and the viscoelasticity determined. Stress relaxation data were modelled according to Maxwell. Physical data were compared with protein and sulfated GAGs composition and ultrastructure SEM. We show that the skin-ECM relaxed faster and had a lower elastic modulus than the lung-ECM and the LV-ECM. The skin-ECM had two Maxwell elements, the lung-ECM and the LV-ECM had three. The skin-ECM had a higher number of sulfated GAGs, and a highly porous surface, while both the LV-ECM and the lung-ECM had homogenous surfaces with localized porous regions. Our results show that the elasticity of ECM hydrogels, but also their viscoelastic relaxation and gelling behavior, was organ dependent. Part of these physical features correlated with their biochemical composition and ultrastructure.

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Abstract 12: EMMPRIN-Targeted Magnetic Nanoparticles for in vivo Visualization and Regression of Acute Myocardial Infarction in a Model of Acute Coronary Artery Occlusion

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.12 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Irene Cuadrado ◽

Maria Jose Garcia Miguel ◽

Irene Herruzo ◽

Mari Carmen Turpin ◽

Ana Martin ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Extracellular Matrix ◽

Coronary Artery ◽

Left Ventricle ◽

Infarct Size ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Gadolinium Enhancement

Extracellular matrix metalloproteinase inducer EMMPRIN, is highly expressed in patients with acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including MMP-9 and MMP-13. To prevent Extracellular matrix degradation and cardiac cell death we targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles with an EMMPRIN binding peptide AP9 conjugated (NAP9), or an AP9 scramble peptide as a negative control (NAPSC). NAP9 binds to endogenous EMMPRIN as detected by confocal microscopy of cardiac myocytes and macrophages incubated with NAP and NAPSC in vitro, and in vivo in mouse hearts subjected to left anterior descending coronary artery occlusion (IV injection 50mγ/Kg NAP9 or NAP9SC). Administration of NAP9 at the same time or 1 hour after AMI reduced infarct size over a 20% respect to untreated and NAPSC injected mice, recovered left ventricle ejection fraction (LVEF) similar to healthy controls, and reduced EMMPRIN downstream MMP9 expression. In magnetic resonance scans of mouse hearts 2 days after AMI and injected with NAP9, we detected a significant gadolinium enhancement in the left ventricle respect to non-injected mice and to mice injected with NAPSC. Late gadolinium enhancement assays exhibited NAP9-mediated left ventricle signal enhancement as early as 30 minutes after nanoprobe injection, in which a close correlation between the MRI signal enhancement and left ventricle infarct size was detected. Taken together, these results point EMMPRIN targeted nanoprobes as a new tool for the treatment of AMI.

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Endogenous Estrogen-Mediated Heme Oxygenase Regulation in Experimental Menopause

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/429713 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 19

Author(s):

Anikó Pósa ◽

Renáta Szabó ◽

Anett Csonka ◽

Médea Veszelka ◽

Anikó Magyariné Berkó ◽

...

Keyword(s):

Left Ventricle ◽

Heme Oxygenase ◽

Protoporphyrin Ix ◽

Control Group ◽

St Segment ◽

Female Wistar Rats ◽

Endogenous Estrogen ◽

Estrogen Depletion ◽

Cardiac Left Ventricle

Estrogen deficiency is one of the main causes of age-associated diseases in the cardiovascular system. Female Wistar rats were divided into four experimental groups: pharmacologically ovariectomized, surgically ovariectomized, and 24-month-old intact aging animals were compared with a control group. The activity and expression of heme oxygenases (HO) in the cardiac left ventricle, the concentrations of cardiac interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α), the myeloperoxidase (MPO) activity in the cardiac left ventricle, and the effects of heme oxygenase blockade (by 24-hour and 1-hour pretreatment with tin-protoporphyrin IX, SnPP) on the epinephrine and phentolamine-induced electrocardiogram ST segment changesin vivowere investigated. The cardiac HO activity and the expression of HO-1 and HO-2 were significantly decreased in the aged rats and after ovariectomy. Estrogen depletion was accompanied by significant increases in the expression of IL-6 and TNF-α. The aged and ovariectomized animals exhibited a significantly elevated MPO activity and a significant ST segment depression. After pretreatment with SnPP augmented ST segment changes were determined. These findings demonstrate that the sensitivity to cardiac ischemia in estrogen depletion models is associated with suppression of the activity and expression of the HO system and increases in the secretion of proinflammatory cytokines and biomarkers.

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Viscoelastic properties of tissue conditioners ? stress relaxation test using Maxwell model analogy

Journal of Oral Rehabilitation ◽

10.1111/j.1365-2842.1990.tb00021.x ◽

1990 ◽

Vol 17 (4) ◽

pp. 365-375 ◽

Cited By ~ 13

Author(s):

H. MURATA ◽

N. SHIGETO ◽

T. HAMADA

Keyword(s):

Stress Relaxation ◽

Viscoelastic Properties ◽

Maxwell Model ◽

Relaxation Test ◽

Stress Relaxation Test

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Advanced Material Catheter (AMCath), a minimally invasive endocardial catheter for the delivery of fast-gelling covalently cross-linked hyaluronic acid hydrogels

Journal of Biomaterials Applications ◽

10.1177/0885328218805878 ◽

2018 ◽

Vol 33 (5) ◽

pp. 681-692 ◽

Cited By ~ 13

Author(s):

Eimear B Dolan ◽

Lenka Kovarova ◽

Hugh O'Neill ◽

Martin Pravda ◽

Romana Sulakova ◽

...

Keyword(s):

Hyaluronic Acid ◽

Left Ventricle ◽

Minimally Invasive ◽

Viscoelastic Properties ◽

Advanced Materials ◽

Regenerative Therapy ◽

Injectable Hydrogels ◽

Adipose Derived Stem Cell

Injectable hydrogels that aim to mechanically stabilise the weakened left ventricle wall to restore cardiac function or to deliver stem cells in cardiac regenerative therapy have shown promising data. However, the clinical translation of hydrogel-based therapies has been limited due to difficulties injecting them through catheters. We have engineered a novel catheter, Advanced Materials Catheter (AMCath), that overcomes translational hurdles associated with delivering fast-gelling covalently cross-linked hyaluronic acid hydrogels to the myocardium. We developed an experimental technique to measure the force required to inject such hydrogels and determined the mechanical/viscoelastic properties of the resulting hydrogels. The preliminary in vivo feasibility of delivering fast-gelling hydrogels through AMCath was demonstrated by accessing the porcine left ventricle and showing that the hydrogel was retained in the myocardium post-injection (three 200 μL injections delivered, 192, 204 and 183 μL measured). However, the mechanical properties of the hydrogels were reduced by passage through AMCath (≤20.62% reduction). We have also shown AMCath can be used to deliver cardiopoietic adipose-derived stem cell-loaded hydrogels without compromising the viability (80% viability) of the cells in vitro. Therefore, we show that hydrogel/catheter compatibility issues can be overcome as we have demonstrated the minimally invasive delivery of a fast-gelling covalently cross-linked hydrogel to the beating myocardium.

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An In-Vivo Measurement and Analysis of Viscoelastic Properties of the Spinal Cord of Cats

Journal of Biomechanical Engineering ◽

10.1115/1.3108415 ◽

1988 ◽

Vol 110 (2) ◽

pp. 115-122 ◽

Cited By ~ 45

Author(s):

Guan-Liang Chang ◽

Tin-Kan Hung ◽

William W. Feng

Keyword(s):

Spinal Cord ◽

Stress Relaxation ◽

Viscoelastic Properties ◽

Nonlinear Characteristics ◽

In Vivo Measurement ◽

Recovery Curves ◽

Measurement And Analysis ◽

Linear Viscoelastic ◽

Prolonged Stress

An in-vivo experimental technique was employed to determine the linear and nonlinear characteristics of viscoelastic properties of the spinal cord of anesthetized cats. The stress relaxation and recovery curves were reproducible in a group of cat experiments. The data of linear viscoelastic properties were used to develop a power law model with Boltzmann’s convolution integral. The model was capable of predicting a prolonged stress relaxation and recovery curve. For larger deformation, the results were quantified using a nonlinear analysis of viscoelastic response of the spinal cord under the uniaxial experiment.

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Desmopressin (DDAVP) Enhances Platelet Adhesion to the Extracellular Matrix of Cultured Human Endothelial Cells through Increased Expression of Tissue Factor

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656088 ◽

1997 ◽

Vol 77 (05) ◽

pp. 0975-0980 ◽

Cited By ~ 23

Author(s):

Angel Gálvez ◽

Goretti Gómez-Ortiz ◽

Maribel Díaz-Ricart ◽

Ginés Escolar ◽

Rogelio González-Sarmiento ◽

...

Keyword(s):

Extracellular Matrix ◽

Endothelial Cells ◽

Tissue Factor ◽

Platelet Adhesion ◽

Umbilical Vein ◽

Procoagulant Activity ◽

Experimental Conditions ◽

Chromogenic Assay

SummaryThe effect of desmopressin (DDAVP) on thrombogenicity, expression of tissue factor and procoagulant activity (PCA) of extracellular matrix (ECM) generated by human umbilical vein endothelial cells cultures (HUVEC), was studied under different experimental conditions. HUVEC were incubated with DDAVP (1, 5 and 30 ng/ml) and then detached from their ECM. The reactivity towards platelets of this ECM was tested in a perfusion system. Coverslips covered with DD A VP-treated ECMs were inserted in a parallel-plate chamber and exposed to normal blood anticoagulated with low molecular weight heparin (Fragmin®, 20 U/ml). Perfusions were run for 5 min at a shear rate of 800 s1. Deposition of platelets on ECMs was significantly increased with respect to control ECMs when DDAVP was used at 5 and 30 ng/ml (p <0.05 and p <0.01 respectively). The increase in platelet deposition was prevented by incubation of ECMs with an antibody against human tissue factor prior to perfusion. Immunofluorescence studies positively detected tissue factor antigen on DDAVP derived ECMs. A chromogenic assay performed under standardized conditions revealed a statistically significant increase in the procoagulant activity of the ECMs produced by ECs incubated with 30 ng/ml DDAVP (p <0.01 vs. control samples). Northern blot analysis revealed increased levels of tissue factor mRNA in extracts from ECs exposed to DDAVP. Our data indicate that DDAVP in vitro enhances platelet adhesion to the ECMs through increased expression of tissue factor. A similar increase in the expression of tissue factor might contribute to the in vivo hemostatic effect of DDAVP.

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