Frontier Institute of Science and Technology, and State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University , Xi'an 710049, China.
Department of Biomedical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
ACS Nano. 2017 Jun 27;11(6):5646-5659. doi: 10.1021/acsnano.7b01062. Epub 2017 Jun 7.
Mimicking the anisotropic cardiac structure and guiding 3D cellular orientation play a critical role in designing scaffolds for cardiac tissue regeneration. Significant advances have been achieved to control cellular alignment and elongation, but it remains an ongoing challenge for engineering 3D cardiac anisotropy using these approaches. Here, we present a 3D hybrid scaffold based on aligned conductive nanofiber yarns network (NFYs-NET, composition: polycaprolactone, silk fibroin, and carbon nanotubes) within a hydrogel shell for mimicking the native cardiac tissue structure, and further demonstrate their great potential for engineering 3D cardiac anisotropy for cardiac tissue engineering. The NFYs-NET structures are shown to control cellular orientation and enhance cardiomyocytes (CMs) maturation. 3D hybrid scaffolds were then fabricated by encapsulating NFYs-NET layers within hydrogel shell, and these 3D scaffolds performed the ability to promote aligned and elongated CMs maturation on each layer and individually control cellular orientation on different layers in a 3D environment. Furthermore, endothelialized myocardium was constructed by using this hybrid strategy via the coculture of CMs on NFYs-NET layer and endothelial cells within hydrogel shell. Therefore, these 3D hybrid scaffolds, containing NFYs-NET layer inducing cellular orientation, maturation, and anisotropy and hydrogel shell providing a suitable 3D environment for endothelialization, has great potential in engineering 3D cardiac anisotropy.
模拟各向异性的心脏结构和引导 3D 细胞方向在设计用于心脏组织再生的支架方面起着关键作用。已经取得了重大进展来控制细胞的排列和伸长，但使用这些方法来构建 3D 心脏各向异性仍然是一个持续的挑战。在这里，我们提出了一种基于排列的导电纳米纤维纱线网络 (NFYs-NET，组成：聚己内酯、丝素蛋白和碳纳米管) 的 3D 混合支架，用于模拟天然心脏组织结构，并进一步证明了它们在工程 3D 心脏各向异性方面用于心脏组织工程的巨大潜力。结果表明，NFYs-NET 结构可控制细胞方向并增强心肌细胞 (CMs) 的成熟。然后通过将 NFYs-NET 层封装在水凝胶壳内来制造 3D 混合支架，这些 3D 支架具有在每个层上促进排列和伸长的 CMs 成熟的能力，并在 3D 环境中单独控制不同层上的细胞方向。此外，通过在 NFYs-NET 层上培养 CMs 和在水凝胶壳内培养内皮细胞，使用这种混合策略构建了内皮化的心肌。因此，这些 3D 混合支架包含 NFYs-NET 层，可诱导细胞方向、成熟和各向异性，以及水凝胶壳提供适合内皮化的 3D 环境，在构建 3D 心脏各向异性方面具有巨大的潜力。
