VEGF-Functionalized Polyelectrolyte Multilayers as Proangiogenic Prosthetic Coatings†

Stimulation of transprosthetic vascularization represents an interesting strategy in implantology to allow rapid tissue integration and finally to avoid prosthetic rejection. To achieve this goal, we modified the surface of porous titanium implants with polyelectrolyte multilayer (PEM) films functionalized with vascular endothelial growth factor (VEGF). Among the two PEM systems investigated, poly(L-lysine)/poly(L-glutamic acid) (PLL/PGA) and poly(allylamine hydrochloride)/poly(sodium 4-styrenesulfonate) (PAH/PSS), the (PAH/PSS) 4 architecture was selected to functionalize porous titanium, both for its high efficiency to adsorb VEGF and for its biocompatibility toward endothelial cells. In an original way, we unambiguously demonstrated that VEGF adsorbed on (PAH/PSS) 4 maintains its bioactivity in vitro and stimulates endothelial cells proliferation. This effect was correlated with specific activation of intracellular signaling pathways induced by successive phosphorylation of the endothelial VEGF receptor VEGFR2 and mitogen-activated protein kinases (MAPK) ERK1/2. By clearly demonstrating the proangiogenic activity of the VEGF-PEM coating in vitro, the present study constitutes a first step toward in vivo application.