Material-based Regulation of the Myofibroblast Phenotype.
From: Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309-0424, USA.
Biomaterials
- Publish Date: Aug 2007
- ISSN: 0142-9612
- Volume: 28
- Issue: 23
- Pages: 3378-87
- Medium: Print
- Language: English
- Citation (JAMA): Cushing Melinda C, Liao Jo-Tsu, Jaeggli Michael P, et al. Material-based Regulation of the Myofibroblast Phenotype.. Biomaterials Aug 2007;28:3378-87
Abstract
Fibroblast growth factor receptor (FGFR) activation by basic fibroblast growth factor (FGF-2) serves to naturally repress the myofibroblast activation of valvular interstitial cells (VICs). Co-receptors for FGF-2, the heparan sulfate proteoglycans (HSPGs), are key participants in the formation of active FGF-2 signaling complexes. Bioactive environments regulating the myofibroblast phenotype were created by utilizing heparin glycosaminoglycan as a competitive inhibitor of HSPGs. First, soluble heparin was delivered to compete with cell-surface HSPG for the binding of FGF-2. Exogenous soluble heparin prevented serum-dependent activation of the classic mitogen-activated protein kinase (MAPK) and induced myofibroblast alpha smooth muscle actin (alphaSMA) expression and collagen production. Next, heparin-functionalized hydrogel cell substrates were polymerized from vinyl-modified precursors and rendered adhesive through incorporation of RGDS peptide. Culture of VICs on heparin-modified gels induced alphaSMA expression and inhibited MAPK activity compared to control gel substrates lacking heparin. Additionally, heparin-functionalized gels continued to induce alphaSMA expression in serum-free culture conditions, suggesting that bioactivity was independent of exogenous soluble mediators. Biomaterial scaffolds targeting cell surface growth factor receptors are a promising new direction for regulating cell functions in tissue-engineering applications.
Mesh Headings (Keywords): Actins, Animals, Aortic Valve, Biocompatible Materials, Cells, Cultured, Collagen, Culture Media, Serum-Free, Dose-Response Relationship, Drug, Enzyme Activation, Fibroblast Growth Factor 2, Fibroblasts, Gene Expression Regulation, Heparan Sulfate Proteoglycans, Heparin, Hydrogel, Mitogen-Activated Protein Kinases, Models, Biological, Muscle, Smooth, Phenotype, Receptors, Fibroblast Growth Factor, Signal Transduction, Substrate Specificity, Swine, Tissue Engineering
Check for Full Text / PubMed Unique Identifier (PMID): 17475322
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