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Bioprinting Complex Cartilaginous Structures with Clinically Compliant Biomaterials

机译：使用临床兼容的生物材料对复杂的软骨结构进行生物打印

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摘要

Bioprinting is an emerging technology for the fabrication of patient-specific, anatomically complex tissues and organs. A novel bioink for printing cartilage grafts is developed based on two unmodified FDA-compliant polysaccharides, gellan and alginate, combined with the clinical product BioCartilage (cartilage extracellular matrix particles). Cell-friendly physical gelation of the bioink occurs in the presence of cations, which are delivered by co-extrusion of a cation-loaded transient support polymer to stabilize overhanging structures. Rheological properties of the bioink reveal optimal shear thinning and shear recovery properties for high-fidelity bioprinting. Tensile testing of the bioprinted grafts reveals a strong, ductile material. As proof of concept, 3D auricular, nasal, meniscal, and vertebral disk grafts are printed based on computer tomography data or generic 3D models. Grafts after 8 weeks in vitro are scanned using magnetic resonance imaging and histological evaluation is performed. The bioink containing BioCartilage supports proliferation of chondrocytes and, in the presence of transforming growth factor beta-3, supports strong deposition of cartilage matrix proteins. A clinically compliant bioprinting method is presented which yields patient-specific cartilage grafts with good mechanical and biological properties. The versatile method can be used with any type of tissue particles to create tissue-specific and bioactive scaffolds.
机译：生物打印是一种用于制造患者特定的，解剖学上复杂的组织和器官的新兴技术。基于两种未修饰的符合FDA要求的多糖，结冷胶和藻酸盐，并结合临床产品BioCartilage（软骨细胞外基质颗粒），开发了一种新型的用于印刷软骨移植物的生物墨水。在存在阳离子的情况下，生物墨水会发生细胞友好的物理胶凝作用，这些阳离子可通过共挤出负载有阳离子的瞬态支持聚合物来稳定悬垂结构。生物墨水的流变特性显示出高保真生物打印的最佳剪切稀化和剪切恢复特性。生物印花移植物的拉伸测试显示出坚固，可延展的材料。作为概念证明，基于计算机断层扫描数据或通用3D模型打印3D耳廓，鼻，半月板和椎盘移植物。使用磁共振成像扫描体外8周后的移植物，并进行组织学评估。包含BioCartilage的生物墨水支持软骨细胞的增殖，并在存在转化生长因子β-3的情况下支持软骨基质蛋白的强沉积。提出了一种符合临床要求的生物打印方法，该方法可产生具有良好机械和生物学特性的特定于患者的软骨移植物。通用方法可与任何类型的组织颗粒一起使用，以创建组织特异性和生物活性支架。

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