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

基于 3D 打印水凝胶内变形聚合物的血管网络的制造

• 批准号: 427208737
• 负责人: Professor Dr. Leonid Ionov
• 金额: --
• 依托单位: Lehrstuhl für Biomaterialien
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/427208737?language=en
• 关键词: Fabrication; Vascular; Networks; based; Shape

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.

三维(3D)生物打印已经成为一种通用的生物制造技术，可以精确控制所生产构件的组成、空间分布和结构。尽管生物打印技术具有巨大的潜力，但当前方法最关键的挑战之一是打印中空的管状和血管结构。最近，4D生物制造被引入作为3D打印的扩展，其中触发的结构变化可以随着时间的推移(这是第四维)而发生，在管状结构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能用于制造生物医学应用的血管网络。我们将克服目前的障碍，基于嵌入在生物富含的3D水凝胶支架中的形状变化的生物相容聚合物来构建血管网络。形状变化的结构将允许生产网络的基本元素，如扭结管和Y形以及T形接头。将形状、折叠方向和折叠顺序可调的两个变形层折叠起来，即可实现扭结和连接元素。这些层将被实施在工程蜘蛛丝水凝胶中，作为细胞的基质/支架。该项目的主要目标是：(I)建立用于打印复杂形状变化结构的生物相容性材料；(Ii)形状变化的研究和控制方法的建立；(Iii)将其应用于三维生物软化蜘蛛丝水凝胶中，并研究打印和形状变化对细胞活力的影响；以及(Iv)测试血管网络的体外功能。该项目结合了材料合成、形状变化分析、3D水凝胶打印以及细胞对材料变化的响应研究。最终的目标是建立制造血管化人工组织的新工具。