Biofabrication of a prevascularized functional trachea substitute

预血管化功能性气管替代物的生物制造

• 批准号: 256933203
• 负责人: Professor Dr.-Ing. Horst Fischer
• 金额: --
• 依托单位: Lehr- und Forschungsgebiet Zahnärztliche Werkstoffkunde und Biomaterialforschung
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/256933203?language=en
• 关键词: Biofabrication; prevascularized; functional; trachea; substitute

3D printing technologies enable a rapid additive manufacturing that ensures high spatial resolution and complexity of generated parts. Applied on the field of tissue engineering, 3D printing technologies show high potential for the generation of artificial organs which comprise cells and hydrogels and mimic the complexity of natural tissue in structure and composition. A trachea for example consists of several different cell types and different functional tissue types such as muscle, connective tissue, and cartilage.The research project proposed here as a continuation of the project TracheaPrint is based on the hypothesis that the tubular structure of a trachea can be resembled in a 3D drop-on-demand printing procedure. The printing includes two different types of hydrogels: a cell-laden hydrogel blend of agarose and type I collagen and further a cell-free hydrogel that resembles function and shape of native tracheal cartilage. The agarose-collagen blend already proved its printability and high angiogenic potential in the first phase of the project using a co-culture of human endothelial cells and fibroblasts. Particularly, we focus in the second phase of the project on the advancement of a cartilage substitute based on polyethylene glycol (PEG) which forms a hydrogel with tunable mechanical properties. We intend to further shorten the gelation time of a PEG-based hydrogel using a click-chemistry approach avoiding the cytotoxic effect of photo-crosslinkers. The research project includes studies on the cell induced remodeling and tissue maturation in vitro and its influence on angiogenesis and the expression of proangiogenic markers. Furthermore, the integration of pre-vascularized hydrogel samples in a CAM-model will be investigated. Moreover, a novel membrane printing technology best suitable for the specific application will be elaborated and combined with the existing micro-valve based printer. Finally, a cell-laden trachea substitute is printed and cultured in two-step incubation in a pulsatile bioreactor. Additionally, the construct will be epithelialized at the inner surface using a spraying technique. Furthermore, we investigate the general feasibility of employing 3D-bioreactors for tissue engineering of layer-by-layer bioprinted tubular structures. The scientific findings from this project could subsequently be used to develop individualized trachea substitutes.

3D打印技术可实现快速的增材制造，以确保生成的零件的高空间分辨率和复杂性。 3D打印技术应用于组织工程领域，在人工器官的产生中显示出很高的潜力，该器官包含细胞和水凝胶，并模仿结构和组成中天然组织的复杂性。例如，气管由几种不同的细胞类型和不同的功能组织类型组成，例如肌肉，结缔组织和软骨。此处提出的作为项目气管延续的研究项目基于以下假设：在3D滴定的滴定印刷过程中，气管的管状结构可以类似于气管的管状结构。打印包括两种不同类型的水凝胶：琼脂糖和I型胶原蛋白的含细胞水凝胶混合物，以及与天然气管软骨的功能和形状相似的无细胞水凝胶。琼脂糖 - 胶原蛋白混合物已经证明了其在项目的第一阶段使用人内皮细胞和成纤维细胞共文化的可打印性和高血管生成潜力。特别是，我们将重点放在项目的第二阶段上，基于基于聚乙二醇（PEG）的软骨替代品的发展，该乙二醇（PEG）形成具有可调机械性能的水凝胶。我们打算使用点击化学方法进一步缩短基于PEG的水凝胶的凝胶时间，以避免光化交联链接的细胞毒性效应。该研究项目包括有关细胞在体外诱导的重塑和组织成熟的研究及其对血管生成和促血管生成标记的影响。此外，将研究血管前水凝胶样品在CAM模型中的整合。此外，一种最适合特定应用程序的新型膜打印技术将被详细说明并与现有的基于微阀的打印机结合使用。最后，在脉动生物反应器中将载有细胞的气管替代物印刷并在两步孵育中培养。此外，该构建体将使用喷涂技术在内表面上进行上皮化。此外，我们研究了使用3D比较反应器进行逐层生物打印管结构的组织工程的一般可行性。该项目的科学发现随后可用于开发个性化的气管替代品。