Department of Materials Science and Engineering, Monash Institute of Medical Engineering, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
Tissue Engineering + Biofabrication, Department of Health Sciences and Technology, ETH Zürich, Switzerland.
Biomater Sci. 2020 Mar 17;8(6):1711-1725. doi: 10.1039/c9bm01524h.
The encapsulation of cells into microgels is attractive for applications in tissue regeneration. While cells are protected against shear stress during injection, the assembly of microgels after injection into a tissue defect also forms a macroporous scaffold that allows effective nutrient transport throughout the construct. However, in most of current strategies that form microgel-based macroporous scaffold or higher-order structures, cells are seeded during or post the assembly process and not microencapsulated in situ. The objective of this study is to investigate the chondrogenic phenotype of microencapsulated fetal chondrocytes in a biocompatible, assembled microgel system vs. bulk gels and to test the stability of the constructs in vivo. Here, we demonstrate that cell microencapsulation leads to increased expression of cartilage-specific genes in a TGF-β1-dependent manner. This correlates, as shown by histological staining, with the ability of microencapsulated cells to deposit cartilaginous matrix after migrating to the surface of the microgels, while keeping a macroscopic granular morphology. Implantation of precultured scaffolds in a subcutaneous mouse model results in vessel infiltration in bulk gels but not in assembled microgels, suggesting a higher stability of the matrix produced by the cells in the assembled microgel constructs. The cells are able to remodel the microgels as demonstrated by the gradual disappearance of the granular structure in vivo. The biocompatible microencapsulation and microgel assembly system presented in this article therefore hold great promise as an injectable system for cartilage repair.
细胞包封到微凝胶中对于组织再生的应用很有吸引力。虽然细胞在注射过程中免受剪切力的影响，但在注射到组织缺陷后，微凝胶的组装也形成了一个大孔支架，允许有效营养物质在整个构建体中运输。然而，在目前大多数形成基于微凝胶的大孔支架或更高阶结构的策略中，细胞是在组装过程中或之后被播种的，而不是原位微封装的。本研究的目的是研究微封装的胎儿软骨细胞在生物相容的组装微凝胶系统中的软骨生成表型与块状凝胶相比，以及测试体内构建体的稳定性。在这里，我们证明细胞微封装以 TGF-β1 依赖的方式导致软骨特异性基因的表达增加。这与组织学染色结果相关，表明微封装细胞能够在迁移到微凝胶表面后沉积软骨基质，同时保持宏观颗粒形态。在皮下小鼠模型中预培养支架的植入导致块状凝胶中的血管渗透，但在组装的微凝胶中没有，这表明细胞在组装的微凝胶构建体中产生的基质具有更高的稳定性。细胞能够重塑微凝胶，如体内逐渐消失的颗粒结构所示。因此，本文提出的这种生物相容的微封装和微凝胶组装系统作为一种可注射的软骨修复系统具有很大的潜力。
