Hierarchical scaffold design is a crucial parameter to develop appropriate tissue characteristics in the different layers of a vessel. The natural layers of the human vessel, e.g. the tunica intima and the tunica media, can be engineered in bi-layered tubular scaffolds. These scaffolds must permit the adhesion and formation of a confluent endothelial cell monolayer on the intimal side to avoid occlusion via thrombosis. In the medial layer, vascular smooth muscle cell (vSMC) stacking and circumferential alignment must be recapitulated to ensure the contractile function of the vessel. To date, fabrication of an dense luminal fibrous scaffold layer for endothelialization combined with an open fibrous layer for full population by vSMCs with close cell-cell contact throughout the medial layer, remains a challenge in bi-layered scaffolds.<br/>To address these limitations, we present a fabrication approach that combines hierarchically layered scaffold design with the possibility to control structural orientation within the medial layer as guidance for biomimetic vSMC adhesion and growth. This bio-inspired scaffold design was achieved with a novel combination of conventional solution electrospinning and the new melt electrowriting (MEW) technology [1] onto cylindrical targets. The scaffolds consisted of an inner dense randomly oriented layer of single micron diameter fibers, and an oriented outer layer of one order of magnitude thicker fibers and bigger pores. We demonstrate that this vascular graft supported the organization of a continuous luminal endothelial monolayer and multiple oriented layers of vSM-like cells in the outer layer of the graft. Induction of the phenotypic morphology of the endothelium and vSM-like cells was enabled by this specific scaffold hierarchy. This study underlines the importance of the convergence of fabrication techniques to create scaffold designs that can support and control heterotypic cell organization and differentiation, improving vascular tissue engineering strategies.<br/><br/>

Orchestrating cellular organization and phenotype in small diameter bi-layered vascular grafts by heterotypic scaffold design

2019 Fall National Meeting

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