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Material-based regulation of the myofibroblast phenotype

Paper ID Volume ID Publish Year Pages File Format Full-Text
9890 652 2007 10 PDF Available
Material-based regulation of the myofibroblast phenotype

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 (αSMA) 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 αSMA expression and inhibited MAPK activity compared to control gel substrates lacking heparin. Additionally, heparin-functionalized gels continued to induce αSMA 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.

Cardiac valve tissue engineering; Cell signalling; Fibroblast growth factor receptor; MAPK; Heparin; Hydrogel
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Material-based regulation of the myofibroblast phenotype
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 28, Issue 23, August 2007, Pages 3378–3387
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Physical Sciences and Engineering Chemical Engineering Bioengineering