1. Discrete microstructural cues for the attenuation of fibrosis following myocardial infarction.
- Author
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Pinney JR, Du KT, Ayala P, Fang Q, Sievers RE, Chew P, Delrosario L, Lee RJ, and Desai TA
- Subjects
- 3T3 Cells, Animals, Biocompatible Materials administration & dosage, Collagen analysis, Female, Fibroblasts cytology, Fibrosis, Methacrylates administration & dosage, Mice, Microtechnology, Polyethylene Glycols administration & dosage, Rats, Sprague-Dawley, Tissue Engineering, Biocompatible Materials therapeutic use, Methacrylates therapeutic use, Myocardial Infarction pathology, Myocardial Infarction therapy, Myocardium pathology, Polyethylene Glycols therapeutic use
- Abstract
Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. We have developed a therapeutic materials strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructures to mechanically alter the microenvironment. Polymeric microstructures were fabricated using photolithographic techniques and studied in a three-dimensional culture model of the fibrotic environment and by direct injection into the infarct zone of adult rats. Here, we show dose-dependent down-regulation of expression of genes associated with the mechanical fibrotic response in the presence of microstructures. Injection of this microstructured material into the infarct zone decreased levels of collagen and TGF-β, increased elastin deposition and vascularization in the infarcted region, and improved functional outcomes after six weeks. Our results demonstrate the efficacy of these discrete anti-fibrotic microstructures and suggest a potential therapeutic materials approach for combatting pathologic fibrosis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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