The behavior of tissue resident cells can be influenced by the spatial arrangement of cellular interactions. Therefore, it is of significance to precisely control the spatial organization of various cells within multicellular constructs. It remains challenging to construct a versatile multicellular scaffold with ordered spatial organization of multiple cell types. Herein, a modular multicellular tissue engineering scaffold with ordered spatial distribution of different cell types is constructed by assembling varying cell-laden modules. Interestingly, the modular scaffolds can be disassembled into individual modules to evaluate the specific contribution of each cell type in the system. Through assembling cell-laden modules, the macrophage-mesenchymal stem cell (MSC), endothelial cell-MSC, and chondrocyte-MSC co-culture models are successfully established. The in vitro results indicate that the intercellular cross-talk can promote the proliferation and differentiation of each cell type in the system. Moreover, MSCs in the modular scaffolds may regulate the behavior of chondrocytes through the nuclear factor of activated T-Cells (NFAT) signaling pathway. Furthermore, the modular scaffolds loaded with co-cultured chondrocyte-MSC exhibit enhanced regeneration ability of osteochondral tissue, compared with other groups. Overall, this work offers a promising strategy to construct a multicellular tissue engineering scaffold for the systematic investigation of intercellular cross-talk and complex tissue engineering.

中文翻译：

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用于多细胞组织工程的组装/拆卸模块化支架

组织驻留细胞的行为可能受到细胞相互作用的空间排列的影响。因此，精确控制多细胞结构内各种细胞的空间组织具有重要意义。构建具有多种细胞类型有序空间组织的多功能多细胞支架仍然具有挑战性。在此，通过组装不同的细胞负载模块构建了具有不同细胞类型有序空间分布的模块化多细胞组织工程支架。有趣的是，模块化支架可以拆卸成单独的模块，以评估系统中每种细胞类型的具体贡献。通过组装细胞模块，成功建立了巨噬细胞-间充质干细胞（MSC）、内皮细胞-MSC和软骨细胞-MSC共培养模型。体外结果表明，细胞间串扰可以促进系统中每种细胞类型的增殖和分化。此外，模块化支架中的间充质干细胞可以通过活化T细胞核因子（NFAT）信号通路调节软骨细胞的行为。此外，与其他组相比，装载共培养软骨细胞-MSC的模块化支架表现出增强的骨软骨组织再生能力。总体而言，这项工作为构建多细胞组织工程支架以系统研究细胞间串扰和复杂组织工程提供了一种有前途的策略。