Discrete microstructural cues for the attenuation of fibrosis following myocardial infarction
Autor: | Kim T. Du, Lawrence Delrosario, Tejal A. Desai, Randall J. Lee, Perla Ayala, James R. Pinney, Patrick Chew, Richard E. Sievers, Qizhi Fang |
---|---|
Rok vydání: | 2014 |
Předmět: |
Pathology
medicine.medical_specialty Materials science Culture model Biophysics Myocardial Infarction Bioengineering Biocompatible Materials Article Cardiac dysfunction Polyethylene Glycols Biomaterials Rats Sprague-Dawley Mice Tissue engineering Fibrosis medicine Animals Myocardial infarction biology Tissue Engineering Myocardium 3T3 Cells Fibroblasts medicine.disease Mechanics of Materials Ceramics and Composites biology.protein Methacrylates Microtechnology Myocardial fibrosis Female Collagen Elastin Infarct zone |
Zdroj: | Biomaterials. 35(31) |
ISSN: | 1878-5905 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |