Recent advances in bioengineering and materials science have enabled the 3D printing of biocompatible materials and living cells for purposes of producing human tissues. However, there is currently still a shortage of materials that are suitable both in terms of their mechanical properties and their bioactivity. In addition, technical obstacles, such as the vascularization of generated tissues, continue to preclude the widespread clinical relevance of 3D printed tissues. Herein, we present a 3D-printing-enabled platform for the fabrication of living-composite vascular models from stimuli-responsive hydrogels with <i>in situ</i> copolymerized functional additives. We have developed a series of 3D printed coaxial nozzles through which hydrogel materials can in turn be 3D printed. Our approach utilizes the modification of Pluronic® F-127 with methacrylate end-groups to enable photoinitiated crosslinking. Unmodified and modified F-127 based hydrogels are coextruded through the 3D printed coaxial nozzles in a core-shell configuration. Post-print crosslinking of the shell and dissolution of the core yields tubular constructs with well-defined lumen diameters ranging from around 200 µm to 2 cm, as dictated by the nozzle diameters. Tubular constructs fabricated in this way can be further functionalized via covalent coupling of integrin-recognized oligopeptides to co-crosslinked additives which are incorporated into the shell hydrogel prior to extrusion and copolymerized into the network thereafter. Following oligopeptide coupling, tubular constructs were endothelialized with human microvascular endothelial cells. The cooperative application of custom coaxial nozzles and stimuli-responsive hydrogel materials, tailored to promote cell-adhesion represents a highly versatile platform capable of producing macro- and microscale living-composite vascular models.

Modular 3D-printing-enabled platform for the fabrication of living-composite models of human vasculature

255th National Meeting (2018)

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