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

三维（3D）生物打印已经成为一种多功能的生物制造技术，可以精确控制所生产结构的组成、空间分布和结构。尽管生物打印技术具有巨大的潜力，但当前方法的最关键挑战之一是打印中空管状和血管结构。最近，4D生物制造作为3D打印的延伸被引入，其中触发的结构变化可以随时间发生（这是第四维），在管状构造的制造中提供了许多优点，例如高分辨率和不需要牺牲模板。然而，目前的4D生物打印技术到目前为止还不适合制造用于生物医学应用的血管网络。我们将克服目前的障碍，并基于嵌入生物制造3D水凝胶支架中的形状变化生物相容性聚合物制造血管网络。形状改变的结构将允许产生网络的基本元素，如扭结管和Y-以及T-接头。通过折叠两个形状变化层来实现扭结和接合元件，这两个形状变化层具有可调节的形状、折叠方向和折叠顺序。这些层将在工程蜘蛛丝水凝胶中实现，作为细胞的基质/支架。该项目的主要目标是：（一）确定用于印刷复杂形状变化结构的生物相容性材料;（二）调查形状变化并确定控制方法;（iii）其在3D生物制造的蜘蛛丝水凝胶中的实施和研究打印和形状转化对细胞活力的影响，和（iv）测试血管网络的体外功能性。该项目结合了材料合成，形状转换分析，3D水凝胶打印以及对材料变化的细胞反应的研究。其最终目标是建立新的血管化人工组织的制造工具。

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.