3D Printed Bioreactors for Cell Culture

用于细胞培养的 3D 打印生物反应器

• 批准号: 9279981
• 负责人: John P Fisher
• 金额: $ 33.86万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-15 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9279981
• 关键词: 3D Print; Address; Allogenic; Alpha Cell; Architecture; Area; Autologous; Biological Assay; Bioreactors; Bone Injury; Bone Tissue; Bone Transplantation; Caliber; Cell Communication; Cell Count; Cell Culture Techniques; Cell Differentiation process; Cell Proliferation; Cell Survival; Cells; Coculture Techniques; Communities; Complex; Computer-Aided Design; Culture Techniques; Custom; Development; Encapsulated; Endothelial Cells; Engineering; Ensure; Enterochromaffin Cells; Environment; Gases; Gelatin; Gene Expression; Geometry; Growth; Harvest; Housing; Human; Hydrogels; Immune response; Implant; In Vitro; Incidence; Injury; Liquid substance; Location; Mesenchymal Stem Cells; Modeling; Nutrient; Organ Transplantation; Osteoblasts; Oxygen; Pathway interactions; Perfusion; Phase; Phenotype; Polymers; Polystyrenes; Population; Printing; Production; Retrieval; Site; Source; Stem cells; Structure; Surface; System; Tissue Engineering; Tissues; Translating; Trypsin; Tubular formation; Work; base; biodegradable polymer; biomaterial compatibility; bone; bone engineering; caprolactone; cost; design; dispase; dynamic system; flexibility; in vivo; medical complication; mimetics; novel; repaired; scaffold; shear stress; substantia spongiosa; three dimensional cell culture; tool

Project Summary Traditional treatments for bone injuries have significant limitations. While over one million allogenic and autologous bone grafting procedures are performed each year, significant incidences of medical complications - often involving modest viability, poor integration, or an immune response - still occur. Therefore, the flexibility provided by an in vitro cultured, engineered tissue provides an excellent avenue to repair and replace damaged bone tissue. This approach involves seeding and growing a cell source on a scaffold and implanting the cell-laden construct into the injury site. However, the culture of large volume engineered tissues - and particularly cell viability, expansion, proliferation, and differentiation in these large tissues - is limited by current culture techniques. To address this concern, TR&D1 aims to develop a 3D printed (3DP) bioreactor as a dynamic culture system to control cellular microenvironment and therefore promote cell viability, expansion, proliferation, and differentiation within large engineered constructs. To this end, we have recently developed a tubular perfusion system (TPS) bioreactor that enables the expansion of human mesenchymal stem cells, the differentiation of these cells into osteoblasts, and the subsequent formation of boney tissue. Based on our earlier TPS bioreactor, we will use 3D printing to fabricate specialized bioreactor chambers with variable architecture, controlled flow environments, and spatially located cell populations; thus, we can ensure adequate availability of nutrients and oxygen for the expansion of stem cells within these large constructs. Furthermore, 3D printing control of the spatial location of cell populations will allow us to determine interactions between multiple cell populations, such as mesenchymal stem cells and endothelial cells. Finally, we will utilize the strategies developed in the in vitro 3D bioreactor chambers to fabricate removable, biodegradable scaffolds of engineered bone tissues that are suitable for in vivo application. The results of these studies will deliver a 3DP bioreactor system that can support the growth of large engineered tissues, while also providing a set of tools to develop other, similarly designed, tissue specific bioreactor systems.

项目摘要 传统的骨损伤治疗有重大局限性。而超过一百万个同源性和 每年进行自体骨移植程序 - 通常涉及适度的生存力，累积不良或免疫反应 - 仍会发生。因此，灵活性 由体外培养的工程组织提供 受损的骨组织。这种方法涉及在脚手架上播种和生长细胞源 富含细胞的构造中的损伤部位。但是，大量工程组织的培养 特别是细胞活力，膨胀，增殖和分化 - 受电流的限制 文化技术。为了解决这一问题，TR＆D1的目标是开发3D印刷（3DP）生物反应器 动态培养系统控制细胞微环境，从而促进细胞活力，膨胀， 扩散和大型工程结构内的分化。为此，我们最近开发了 管状灌注系统（TPS）生物反应器，使人间充质干细胞的扩张， 这些细胞分化为成骨细胞，并随后形成骨组织。基于我们 早期的TPS生物反应器，我们将使用3D打印来制造具有可变的专业生物反应室 架构，受控的流动环境和空间位置的细胞种群；因此，我们可以确保 在这些大型构造中，有足够的养分和氧气可用于干细胞的扩展。 此外，细胞种群空间位置的3D打印控制将使我们能够确定相互作用 在多个细胞群体（例如间充质干细胞和内皮细胞）之间。最后，我们将使用 在体外3D生物反应室中制定的策略以制造可移动的可生物降解脚手架 适合体内应用的工程骨组织。这些研究的结果将提供 3DP生物反应器系统，可以支持大型工程组织的生长，同时还提供一组 开发其他类似设计的，特定于组织的生物反应器系统的工具。