The classical 3D-printed scaffolds have attracted enormous interests in bone regeneration due to the customized structural and mechanical adaptability to bone defects. However, the pristine scaffolds still suffer from the absence of dynamic and bioactive microenvironment that is analogous to natural extracellular matrix (ECM) to regulate cell behaviour and promote tissue regeneration. To address this challenge, we develop a black phosphorus nanosheets-enabled dynamic DNA hydrogel to integrate with 3D-printed scaffold to build a bioactive gel-scaffold construct to achieve enhanced angiogenesis and bone regeneration. The black phosphorus nanosheets reinforce the mechanical strength of dynamic self-healable hydrogel and endow the gel-scaffold construct with preserved protein binding to achieve sustainable delivery of growth factor. We further explore the effects of this activated construct on both human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) as well as in a critical-sized rat cranial defect model. The results confirm that the gel-scaffold construct is able to promote the growth of mature blood vessels as well as induce osteogenesis to promote new bone formation, indicating that the strategy of nano-enabled dynamic hydrogel integrated with 3D-printed scaffold holds great promise for bone tissue engineering.

由于对骨缺损的定制结构和机械适应性，经典的 3D 打印支架在骨再生方面引起了极大的兴趣。然而，原始支架仍然缺乏类似于天然细胞外基质 (ECM) 来调节细胞行为和促进组织再生的动态和生物活性微环境。为了应对这一挑战，我们开发了一种支持黑磷纳米片的动态 DNA 水凝胶，与 3D 打印支架相结合，构建生物活性凝胶支架结构，以实现增强的血管生成和骨再生。黑磷纳米片增强了动态自修复水凝胶的机械强度，并赋予凝胶支架结构保留的蛋白质结合能力，以实现生长因子的可持续输送。我们进一步探讨了这种活化结构对人脐静脉内皮细胞 (HUVEC) 和间充质干细胞 (MSC) 以及临界大小的大鼠颅缺损模型的影响。结果证实凝胶支架结构能够促进成熟血管的生长以及诱导成骨以促进新骨形成，表明纳米动态水凝胶与3D打印支架相结合的策略具有很大的应用前景。骨组织工程。