Engineered microenvironments for synergistic VEGF – Integrin signalling during vascularization

• DOI: 10.1016/j.biomaterials.2017.02.024
• Publication Date: 2017-02-21T21:48:34Z
• Authors: Vladimíra Moulisová; Cristina Gonzalez...; Marco Cantini; Aleixandre Rodrig...; Jessica Weaver; Mercedes Costell; Roser Sabater i S...; Matthew J. Dalby; Andrés J. García; Manuel Salmerón-S...
• Keywords: Male; Vascular Endothelial Growth Factor A; Integrins; Biophysics; Neovascularization, Physiologic; Bioengineering; poly(ethyl acrylate); Article; Biomaterials; 03 medical and health sciences; Human Umbilical Vein Endothelial Cells; Image Processing, Computer-Assisted; Animals; Humans; Phosphorylation; Extracellular Signal-Regulated MAP Kinases; Fibronectin; 0303 health sciences; Tissue Engineering; Protein assembly; Phospholipase C gamma; Vascularization; VEGF; Fibronectins; 3. Good health; Mice, Inbred C57BL; Cellular Microenvironment; Mechanics of Materials; FISICA APLICADA; Focal Adhesion Protein-Tyrosine Kinases; Mutation; Ceramics and Composites; INGENIERIA ELECTRICA; Growth factors; Protein Binding; Signal Transduction

We have engineered polymer-based microenvironments that promote vasculogenesis both in vitro and vivo through synergistic integrin-growth factor receptor signalling. Poly(ethyl acrylate) (PEA) triggers spontaneous organization of fibronectin (FN) into nanonetworks which provide availability critical binding domains. Importantly, the growth (FNIII12-14) integrin (FNIII9-10) regions are simultaneously available on FN fibrils assembled PEA. This material platform promotes integrin/VEGF signalling is highly effective for vascularization events with low concentrations VEGF. VEGF specifically binds to PEA compared control polymers (poly(methyl acrylate), PMA) where remains a globular conformation integrin/GF domains not available. The vasculogenic response human endothelial cells seeded these interfaces (VEGF bound PEA) was significantly improved soluble administration at higher doses. Early onset (PLCγ1 phosphorylation) (ERK1/2 were increased only when PEA, while did influence early Experiments mutant molecules impaired site (FN-RGE) confirmed role via combined In experiments using 3D scaffolds coated implanted murine fat pad demonstrated pro-vascularization by enhanced formation new tissue inside scaffold pores. PEA-driven efficient presentation regenerative medicine applications.