Modulated Fibronectin Anchorage at Polymer Substrates Controls Angiogenesis

Abstract

A set of maleic anhydride copolymer thin films exhibiting well-defined differences in hydrophobicity and reactivity was compared with respect to the capability of supporting angiogenesis of human endothelial cells grown in contact. The physicochemical surface characteristics of the polymer substrates were found to modulate the anchorage of immobilized fibronectin. This was demonstrated to determine whether endothelial cells grow as a monolayer or form capillary networks. Enhanced reorganization of predeposited fibronectin into cell–matrix adhesions and slightly elevated levels of membrane-type matrix metalloproteinase 14 (MMP-14) occurred with weakly bound fibronectin layers where angiogenesis was most obvious. The key role of fibronectin–substrate binding for angiogenesis—under otherwise constant conditions—was further confirmed by the absence of variations in the expression of angiogenesis-related integrins (α_vβ₃) and in the secretion of the metalloproteinase MMP-2. Altogether, the results of this study point at the relevance of physicochemical surface characteristics of polymer materials for the stimulation of angiogenesis.