The effects of monoacrylated poly(ethylene glycol) on the properties of poly(ethylene glycol) diacrylate hydrogels used for tissue engineering.
ABSTRACT This study investigated the effects of poly(ethylene glycol) monoacrylate (PEGMA) on the properties of poly(ethylene glycol) diacrylate (PEGDA)-co-PEGMA hydrogel networks. The PEGMA materials utilized were similar to ligand-linked materials typically copolymerized with PEGDA for use as tissue engineering scaffolds. PEGDA (5-20% wt/wt, 6 kDa) and PEGMA (0-20% wt/wt, 0-43 mM, 5 kDa) were copolymerized by photo-initiated free radical polymerization and the mass swelling ratio and shear modulus of the resulting hydrogels were determined. Increasing the prepolymerization concentration of PEGMA decreased the swelling ratio by up to 42 +/- 1.6% and increased the shear modulus by up to 167 +/- 29.3%, suggesting that PEGMA enhanced gel cross-linking. Analysis of the effective number of cross-linked chains per PEGDA, calculated independently from swelling and mechanical data, indicated each PEGDA participated in more cross-links as PEGMA was added. The results suggest that PEGMA-co-PEGDA gels can be formed with higher concentrations of PEGMA-tethered ligands than previously reported allowing the formation of scaffolds with a rich diversity of biological functionalities without sacrificing the integrity of the gel network.
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ABSTRACT: Angiogenesis is regulated by both soluble growth factors and cellular interactions with the extracellular matrix (ECM). While cell adhesion via integrins has been shown to be required for angiogenesis, the effects of quantitative changes in cell adhesion and spreading against the ECM remain less clear. Here, we show that angiogenic sprouting in natural and engineered three-dimensional matrices exhibited a biphasic response, with peak sprouting when adhesion to the matrix was limited to intermediate levels. Examining changes in global gene expression to determine a genetic basis for this response, we demonstrate a vascular endothelial growth factor (VEGF)-induced upregulation of genes associated with vascular invasion and remodeling when cell adhesion was limited, whereas cells on highly adhesive surfaces upregulated genes associated with proliferation. To explore a mechanistic basis for this effect, we turned to focal adhesion kinase (FAK), a central player in adhesion signaling previously implicated in angiogenesis, and its homologue, proline-rich tyrosine kinase 2 (Pyk2). While FAK signaling had some impact, our results suggested that Pyk2 can regulate both gene expression and endothelial sprouting through its enhanced activation by VEGF in limited adhesion contexts. We also demonstrate decreased sprouting of tissue explants from Pyk2-null mice as compared to wild type mice as further confirmation of the role of Pyk2 in angiogenic sprouting. These results suggest a surprising finding that limited cell adhesion can enhance endothelial responsiveness to VEGF and demonstrate a novel role for Pyk2 in the adhesive regulation of angiogenesis.Experimental Cell Research 08/2011; 317(13):1860-71. · 3.58 Impact Factor