3D bioprinted in vitro bone models

3D 生物打印体外骨模型

• 批准号: 535949855
• 负责人: Dr. Anne Bernhardt
• 金额: --
• 依托单位: Zentrum für Translationale Knochen-, Gelenk- und Weichgewebeforschung
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/535949855?language=en
• 关键词: 3D; bioprinted; vitro; bone; models

In the proposed project, 3D bioprinted in vitro bone models will be generated. Using extrusion-based bioprinting we want to create complex 3D structures mimicking the natural osteon structure. Our ambition is to involve primary human cells instead of immortalised cell lines to finally establish a 3D co-culture model of osteoblasts, osteoclasts, osteocytes and endothelial cells. Crucial points in this projects are 1) the development of an ink supporting both osteocyte differentiation, attachment and spreading of osteoblasts as well as osteoclast differentiation, 2) the spatial arrangement of the different cell species and 3) the inclusion of endothelial cells to study effects of bone cells on vascularization and vice versa. Osteocytes, as regulators of bone remodeling have rarely been involved before in bioprinted structures, due to the limited availability of these cells and their postmitotic character. We want to apply bioprinted human primary osteoblasts and trigger their transition to osteocytes in the printed constructs, since preliminary work on this topic already showed promising results. Osteocyte containing constructs will be seeded with osteoblasts and osteoclasts or osteoclast progenitors to mimic natural bone structure with osteoblasts and osteoclasts at the surface and osteocytes deeply embedded into the bone matrix. We furthermore plan to include components of bone ECM like collagen I and hydroxyapatite into the inks to get a more bone-like model. Finally, core-shell bioprinting will be used to include endothelial cells. Two different approaches will be followed, with endothelial cells in a hydrogel core surrounded by the other cell types or seeded into osteocyte-containing hollow strands. The 3D printed model is intended to test the response of bone tissue to bioactive agents like growth factors, drugs, bioactive ions as well as biomaterials extracts. This would help to reduce animal experiments at least at the early stages of biomaterials and drug development. Furthermore, the model will help to further understand the complex interaction between osteocytes, osteoblasts, osteoclasts and endothelial cells.

在拟议的项目中，将生成3D生物打印体外骨骼模型。使用基于挤出的生物打印，我们希望创建模仿天然骨单位结构的复杂3D结构。我们的目标是利用原代人细胞而不是永生化细胞系，最终建立成骨细胞、破骨细胞、骨细胞和内皮细胞的三维共培养模型。该项目的关键点是1）开发支持骨细胞分化、成骨细胞附着和扩散以及破骨细胞分化的墨水，2）不同细胞种类的空间排列和3）包含内皮细胞以研究骨细胞对血管化的影响，反之亦然。骨细胞作为骨重建的调节因子，由于这些细胞的有限可用性及其有丝分裂后的特性，以前很少参与生物打印结构。我们希望应用生物打印的人类原代成骨细胞，并在打印的结构中触发它们向骨细胞的转变，因为关于这一主题的初步工作已经显示出有希望的结果。含骨细胞的构建体将接种成骨细胞和破骨细胞或破骨细胞祖细胞，以模拟天然骨结构，其中成骨细胞和破骨细胞位于表面，骨细胞深深嵌入骨基质中。我们还计划在墨水中加入骨ECM的成分，如胶原蛋白I和羟基磷灰石，以获得更像骨的模型。最后，核-壳生物打印将用于包括内皮细胞。将遵循两种不同的方法，在水凝胶核心中的内皮细胞被其他细胞类型包围或接种到含有骨细胞的中空股线中。3D打印模型旨在测试骨组织对生物活性剂的反应，如生长因子，药物，生物活性离子以及生物材料提取物。这将有助于减少至少在生物材料和药物开发早期阶段的动物实验。此外，该模型将有助于进一步了解骨细胞，成骨细胞，破骨细胞和内皮细胞之间的复杂相互作用。