The effects of peptide-based modification of alginate on left ventricular remodeling and function after myocardial infarction.
ABSTRACT Adverse cardiac remodeling and dysfunction after myocardial infarction (MI) is associated with (BioLineRx, BL-1040 myocardial implant) excessive damage to the extracellular matrix. Biomaterials, such as the in situ-forming alginate hydrogel, provide temporary support and attenuate these processes. Here, we tested the effects of decorating alginate biomaterial with cell adhesion peptides, containing the sequences RGD and YIGSR, or a non-specific peptide (RGE), in terms of therapeutic outcome soon after MI. The biomaterial (i.e., both unmodified and peptide-modified alginate) solutions retained the ability to flow after cross-linking with calcium ions, and could be injected into 7-day infarcts, where they underwent phase transition into hydrogels. Serial echocardiography studies performed before and 60 days after treatment showed that alginate modification with the peptides reduced the therapeutical effects of the hydrogel, as revealed by the extent of scar thickness, left ventricle dilatation and function. Histology and immunohistochemistry revealed no significant differences in blood vessel density, scar thickness, myofibroblast or macrophage infiltration or cell proliferation between the experimental groups BioLineRx BL-1040 myocardial implant. Our studies thus reveal that the chemical and physical traits of the biomaterial can affect its therapeutical efficacy in attenuating left ventricle remodeling and function, post-MI.
- SourceAvailable from: Preethi BalasubramanianJournal of Biomimetics Biomaterials and Tissue Engineering 12/2011; 1(2):149.
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ABSTRACT: Figure optionsDownload full-size imageDownload high-quality image (99 K)Download as PowerPoint slideAdvanced Drug Delivery Reviews. 01/2014;
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ABSTRACT: Nanoparticles (NPs) have great potential to increase the diagnostic capacity of many imaging modalities. MRI is currently regarded as the method of choice for the imaging of deep tissues, and metal ions, such as calcium ions (Ca2+), are essential ingredients for life. Despite the tremendous importance of Ca2+ for the well-being of living systems, the noninvasive determination of the changes in Ca2+ levels in general, and extracellular Ca2+ levels in particular, in deep tissues remains a challenge. Here, we describe the preparation and contrast mechanism of a flexible easy to prepare and selective superparamagnetic iron oxide (SPIO) NPs for the noninvasive determination of changes in extracellular Ca2+ levels using conventional MRI. We show that SPIO NPs coated with monodisperse and purified alginate, having a specific molecular weight, provide a tool to selectively determine Ca2+ concentrations in the range of 250 µm to 2.5 mm, even in the presence of competitive ions. The alginate-coated magnetic NPs (MNPs) aggregate in the presence of Ca2+, which, in turn, affects the T2 relaxation of the water protons in their vicinity. The new alginate-coated SPIO NP formulations, which have no effect on cell viability for 24 h, allow the detection of Ca2+ levels secreted from ischemic cell cultures and the qualitative examination of the change in extracellular Ca2+ levels in vivo. These results demonstrate that alginate-coated MNPs can be used, at least qualitatively, as a platform for the noninvasive MRI determination of extracellular Ca2+ levels in myriad in vitro and in vivo biomedical applications. Copyright © 2014 John Wiley & Sons, Ltd.NMR in Biomedicine 04/2014; · 3.45 Impact Factor