Abstract
Tissue-engineered anisotropic cell constructs are promising candidates for treating volumetric muscle loss (VML). However, achieving successful cell alignment within macroscale 3D cell constructs for skeletal muscle tissue regeneration remains challenging, owing to difficulties in controlling cell arrangement within a low-viscosity hydrogel. Herein, we propose the concept of a magnetorheological bioink to manipulate the cellular arrangement within a low-viscosity hydrogel. This bioink consisted of gelatin methacrylate (GelMA), iron oxide nanoparticles, and human adipose stem cells (hASCs). The cell arrangement is regulated by the responsiveness of iron oxide nanoparticles to external magnetic fields. A bioprinting process using ring magnets was developed for in situ bioprinting, resulting in well-aligned 3D cell structures and enhanced mechanotransduction effects on hASCs. In vitro analyses revealed upregulation of cellular activities, including myogenic-related gene expression, in hASCs. When implanted into a VML mouse model, the bioconstructs improved muscle functionality and regeneration, validating the effectiveness of the proposed approach.