Multi-scale hierarchical scaffolds with aligned micro-fibers for promoting cell alignment

Cell alignment plays an essential role in cytoskeleton reorganization, extracellular matrix remodeling, and biomechanical properties regulation of tissues such as vascular tissues, cardiac muscles, and tendons. Based on the natural-oriented features of cells in native tissues, various biomimetic scaffolds have been reported with the introduction of well-arranged ultrafine fibers to induce cell alignment. However, it is still a challenge to fabricate scaffolds with suitable mechanical properties, biomimetic microenvironment, and ability to promote cell alignment. In this paper, we propose an integrated 3D printing system to fabricate multi-scale hierarchical scaffolds combined with meso-, micro-, and nano-fibrous filaments, in which the meso-, micro-, and nano-fibers fabricated via fused deposition modeling, melt electrospining writing, and solution electrospining can provide structural support, promote cell alignment, and create a biomimetic microenvironment to facilitate cell function, respectively. The plasma surface modification was performed improve the surface wettability of the scaffolds by measuring the contact angle. The obtained in vitro biological results validate the ability of multi-scale hierarchical scaffolds to enhance cell adhesion and proliferation, and promote cell alignment with the guidance of the aligned microfibers produced via melt electrospining writing in hierarchical scaffolds.