No abstract

Scaffold with controlled porosity constitute a cornerstone in tissue engineering, as a physical support for cell adhesion and growth. In this work, scaffolds of polycaprolactone were synthesized by a modified particle leaching method in order to control porosity and pore interconnectivity; the aim is to observe their influence on the mechanical properties and, in the future, on cell adhesion and proliferation rates. Low molecular weight PEMA beads with an average size of 200 microm were sintered with various compression rates in order to obtain the templates (negatives of the scaffolds). Then the melt polycaprolactone was injected into the porous template under nitrogen pressure in a custom made device. After cooling and solidifying of the melt polymer, the porogen was removed by selective dissolution in ethanol. The porosity and morphology of the scaffold were studied as well as the mechanical properties. Porosities from 60% to 85% were reached; it was found that pore interconnectivity logically increases with increasing porosity, and that mechanical strength decreases with increasing porosity. Because of their interesting properties and interconnected structure, these scaffolds are expected to find useful applications as a cartilage or bone repair material.

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

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