Department of Chemical Engineering, Northeastern University, Boston, Massachusetts 02115, United States.
ACS Appl Mater Interfaces. 2020 Jul 22;12(29):33219-33228. doi: 10.1021/acsami.0c07918. Epub 2020 Jul 13.
Cartilage damage caused by aging, repeated overloading, trauma, and diseases can result in chronic pain, inflammation, stiffness, and even disability. Unlike other types of tissues (bone, skin, muscle, etc.), cartilage tissue has an extremely weak regenerative capacity. Currently, the gold standard surgical treatment for repairing cartilage damage includes autografts and allografts. However, these procedures are limited by insufficient donor sources and the potential for immunological rejection. After years of development, engineered tissue now provides a valuable artificial replacement for tissue regeneration purposes. Three-dimensional (3D) bioprinting technologies can print customizable hierarchical structures with cells. The objective of the current work was to prepare a 3D-printed three-layer gradient scaffold with lysine-functionalized rosette nanotubes (RNTK) for improving the chondrogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs). Specifically, biologically inspired RNTKs were utilized in our work because they have unique surface chemistry and biomimetic nanostructure to improve cell adhesion and growth. Different ratios of gelatin methacrylate (GelMA) and poly(ethylene glycol) diacrylate (PEGDA) were printed into a three-layer GelMA-PEGDA gradient scaffold using a stereolithography-based printer, followed by coating with RNTKs. The pores and channels (∼500 μm) were observed in the scaffold. It was found that the population of ADSCs on the GelMA-PEGDA-RNTK scaffold increased by 34% compared to the GelMA-PEGDA scaffold (control). Moreover, after 3 weeks of chondrogenic differentiation, collagen II, glycosaminoglycan, and total collagen synthesis on the GelMA-PEGDA-RNTK scaffold significantly respectively increased by 59%, 71%, and 60%, as compared to the control scaffold. Gene expression of collagen II α1, SOX 9, and aggrecan in the ADSCs growing on the GelMA-PEGDA-RNTK scaffold increased by 79%, 52%, and 47% after 3 weeks, compared to the controls, respectively. These results indicated that RNTKs are a promising type of nanotubes for promoting chondrogenic differentiation, and the present 3D-printed three-layer gradient GelMA-PEGDA-RNTK scaffold shows considerable promise for future cartilage repair and regeneration.
软骨损伤由衰老、反复过载、创伤和疾病引起，可导致慢性疼痛、炎症、僵硬，甚至残疾。与其他类型的组织（骨骼、皮肤、肌肉等）不同，软骨组织的再生能力极其微弱。目前，修复软骨损伤的金标准手术治疗包括自体移植物和同种异体移植物。然而，这些程序受到供体来源不足和潜在免疫排斥的限制。经过多年的发展，工程组织现在为组织再生目的提供了有价值的人工替代物。三维（3D）生物打印技术可以打印具有细胞的可定制分层结构。本研究的目的是制备具有赖氨酸功能化蔷薇纳米管（RNTK）的 3D 打印三层梯度支架，以提高脂肪间充质干细胞（ADSCs）的软骨分化。具体来说，我们在工作中利用了受生物启发的 RNTKs，因为它们具有独特的表面化学和仿生纳米结构，可以改善细胞的粘附和生长。不同比例的明胶甲基丙烯酰胺（GelMA）和聚乙二醇二丙烯酸酯（PEGDA）通过基于立体光刻的打印机打印成三层 GelMA-PEGDA 梯度支架，然后用 RNTKs 涂层。支架中观察到孔径和通道（∼500 μm）。结果发现，与 GelMA-PEGDA 支架（对照）相比，GelMA-PEGDA-RNTK 支架上 ADSC 的数量增加了 34%。此外，在软骨分化 3 周后，GelMA-PEGDA-RNTK 支架上的胶原蛋白 II、糖胺聚糖和总胶原合成分别比对照支架显著增加了 59%、71%和 60%。在 3 周后，在 GelMA-PEGDA-RNTK 支架上生长的 ADSC 的胶原蛋白 II α1、SOX 9 和聚集蛋白基因表达分别增加了 79%、52%和 47%，与对照相比。这些结果表明，RNTKs 是促进软骨分化的一种很有前途的纳米管类型，目前的 3D 打印三层梯度 GelMA-PEGDA-RNTK 支架在未来的软骨修复和再生方面具有很大的应用潜力。
