Fabrication of Vascular Networks based on Shape-Changing Polymers within 3D printed hydrogels

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Three-dimensional (3D) bioprinting has emerged as a versatile biomanufacturing technology offering precise control over composition, spatial distribution, and architecture of the produced constructs. Despite the tremendous potential of the bioprinting techniques, one of the most critical challenges of the current approaches is the printing of hollow tubular and vascular structures. Recently, 4D biofabrication was introduced as extension of 3D printing wherein triggered structural changes can occur over time (which is the fourth dimension) providing a number of advantages in fabrication of tubular constructs such as high resolution and no need for sacrificial templates. Current 4D bioprinting technologies are however so far not feasible to fabricate vascular networks for biomedical applications. We will overcome the current hurdles and fabricate vascular networks based on shape-changing biocompatible polymers embedded in biofabricated 3D hydrogel scaffolds. The shape-changing constructs will allow production of the essential elements of networks such as kinking tubes and Y- as well as T-junctions. Kinking- and junction-elements will be achieved by folding of two shape-changing layers, which possess an adjustable shape, folding direction, and sequence of folding. These layers will be implemented in engineered spider silk hydrogels serving as a matrix/scaffold for cells. The key objectives of the project are: (i) establishment of biocompatible materials for printing of complex shape-changing structures; (ii) investigation of shape-transformation and establishing of methods to control it; (iii) implementation thereof in 3D biofabricated spider silk hydrogels and investigation of effects of printing and shape-transformation on the viability of cells, and (iv) testing the in vitro functionality of the vascular network. The project combines materials synthesis, analysis of shape transformation, 3D hydrogel printing as well as investigation of cellular response to materials changes. The ultimate goal is to establish new tools for fabrication of vascularized artificial tissues.