Additive manufacturing is a promising method for producing customized 3D bioactive constructs for regenerative medicine. Here, 3D printed highly osteogenic scaffolds using nanoengineered ionic–covalent entanglement ink (NICE) for bone tissue engineering are reported. This NICE ink consists of ionic–covalent entanglement reinforced with Laponite, a 2D nanosilicate (nSi) clay, allowing for the printing of anatomic‐sized constructs with high accuracy. The 3D printed structure is able to maintain high structural stability in physiological conditions without any significant swelling or deswelling. The presence of nSi imparts osteoinductive characteristics to the NICE scaffolds, which is further augmented by depositing pluripotent stem cell‐derived extracellular matrix (ECM) on the scaffolds. This is achieved by stimulating human induced pluripotent stem cell‐derived mesenchymal stem cells (iP‐hMSCs) with 2‐chloro‐5‐nitrobenzanilide, a PPARγ inhibitor that enhances Wnt pathway, resulting in the deposition of an ECM characterized by high levels of collagens VI and XII found in anabolic bone. The osteoinductive characteristics of these bioconditioned NICE (bNICE) scaffolds is demonstrated through osteogenic differentiation of bone marrow derived human mesenchymal stem cells. A significant increase in the expression of osteogenic gene markers as well as mineralized ECM are observed on bioconditioned NICE (bNICE) scaffolds compared to bare scaffolds (NICE). The bioconditioned 3D printed scaffolds provide a unique strategy to design personalized bone grafts for in situ bone regeneration.

中文翻译：

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使用 iP-hMSC 衍生基质调节 3D 打印纳米工程离子共价缠结支架。

增材制造是一种用于生产再生医学定制 3D 生物活性结构的有前途的方法。在此，报道了使用纳米工程离子共价缠结墨水（NICE）用于骨组织工程的 3D 打印高成骨支架。这种 NICE 墨水由离子-共价缠结组成，并用 Laponite（一种 2D 纳米硅酸盐 (nSi) 粘土）增强，可以高精度打印解剖尺寸的结构。3D打印结构能够在生理条件下保持较高的结构稳定性，而不会出现任何明显的膨胀或消膨胀。nSi 的存在赋予 NICE 支架骨诱导特性，通过在支架上沉积多能干细胞衍生的细胞外基质 (ECM) 进一步增强骨诱导特性。这是通过用 2-氯-5-硝基苯甲酰苯胺（一种增强 Wnt 通路的 PPARγ 抑制剂）刺激人诱导多能干细胞来源的间充质干细胞 (iP-hMSC) 来实现的，从而导致以高水平胶原蛋白为特征的 ECM 沉积VI 和 XII 存在于骨合成代谢中。这些生物调理 NICE (bNICE) 支架的骨诱导特性通过骨髓来源的人间充质干细胞的成骨分化得到证实。与裸支架 (NICE) 相比，在生物调节 NICE (bNICE) 支架上观察到成骨基因标记物和矿化 ECM 的表达显着增加。生物调节的 3D 打印支架提供了一种独特的策略来设计用于原位骨再生的个性化骨移植物。