Given the low self-healing capacity of fibrocartilage and hyaline cartilage, tissue engineering holds great promise for the development of new regenerative therapies. However, dedifferentiation of cartilage cells during expansion leads to fibrous tissue instead of cartilage. The purpose of our study was to generate 3D microtissues, spheroids, mimicking the characteristics of native fibrocartilage or articular cartilage to use as modular units for implantation in meniscal and articular cartilage lesions, respectively, within the knee joint. A set of parameters was assessed to create spheroids with a geometry compatible with 3D bioprinting for the creation of a biomimetic cartilage construct. Fibrochondrocytes (FC) and articular chondrocytes (AC) spheroids were created using a high-throughput microwell system. Spheroid morphology, viability, proliferation and extracellular matrix were extensively screened. After 2D expansion, FC and AC dedifferentiated, resulting in a loss of cartilage specific extracellular matrix proteins. Spheroid formation did not result in FC redifferentiation, but did lead to redifferentiation of AC, resulting in microtissues displaying collagen II, aggrecan and glycosaminoglycans. This study demonstrates 3D cartilage mimics that could have a potential application in the next generation of Autologous Chondrocyte Implantation procedures. Moreover, spheroids can be used as building blocks to create cartilage constructs by bioprinting in the future.

中文翻译：

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无支架的微组织形成，增强软骨修复

由于纤维软骨和透明软骨的自愈能力低，因此组织工程学对开发新的再生疗法具有广阔的前景。然而，在膨胀过程中软骨细胞的去分化导致纤维组织而不是软骨。我们研究的目的是生成3D微组织，球体，模仿天然纤维软骨或关节软骨的特征，以用作分别植入膝关节半月板和关节软骨病变的模块单元。评估一组参数以产生具有与3D生物打印兼容的几何形状的球体，以创建仿生软骨构造。使用高通量微孔系统创建了纤维软骨细胞（FC）和关节软骨细胞（AC）球体。球体形态，生存能力，广泛筛选增殖和细胞外基质。2D扩展后，FC和AC去分化，导致软骨特异性细胞外基质蛋白丢失。球体的形成不会导致FC再分化，但会导致AC再分化，从而导致显示胶原II，聚集蛋白聚糖和糖胺聚糖的微组织。这项研究证明了3D软骨模拟物在下一代自体软骨细胞植入手术中可能具有潜在的应用。此外，球体可以用作构建基块，以通过将来的生物打印来创建软骨构造。球体的形成不会导致FC再分化，但会导致AC再分化，从而导致显示胶原II，聚集蛋白聚糖和糖胺聚糖的微组织。这项研究证明了3D软骨模拟物在下一代自体软骨细胞植入手术中可能具有潜在的应用。此外，球体可以用作构建基块，以通过将来的生物打印来创建软骨构造。球体的形成不会导致FC再分化，但会导致AC再分化，从而导致显示胶原II，聚集蛋白聚糖和糖胺聚糖的微组织。这项研究证明了3D软骨模拟物在下一代自体软骨细胞植入手术中可能具有潜在的应用。此外，球体可以用作构建基块，以通过将来的生物打印来创建软骨构造。