Hwangbo Hanjun, Chae SooJung, Ryu Dongryeol, Kim GeunHyung
Department of Precision Medicine, Sungkyunkwan University School of Medicine (SKKU-SOM), Suwon, 16419, Republic of Korea.
Institute of Quantum Biophysics, Department of Biophysics, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea.
Bioact Mater. 2024 Dec 3;45:417-433. doi: 10.1016/j.bioactmat.2024.11.035. eCollection 2025 Mar.
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 bioprinting, resulting in well-aligned 3D cell structures and enhanced mechanotransduction effects on hASCs. 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.
组织工程化各向异性细胞构建体是治疗大面积肌肉损失(VML)的有前途的候选者。然而,由于在低粘度水凝胶中控制细胞排列存在困难,在用于骨骼肌组织再生的宏观3D细胞构建体内实现成功的细胞排列仍然具有挑战性。在此,我们提出了一种磁流变生物墨水的概念,以操纵低粘度水凝胶内的细胞排列。这种生物墨水由甲基丙烯酸明胶(GelMA)、氧化铁纳米颗粒和人脂肪干细胞(hASC)组成。细胞排列通过氧化铁纳米颗粒对外部磁场的响应来调节。开发了一种使用环形磁铁的生物打印工艺用于生物打印,从而形成排列良好的3D细胞结构,并增强了对hASC的机械转导作用。分析显示hASC中细胞活性上调,包括与成肌相关的基因表达。当植入VML小鼠模型中时,生物构建体改善了肌肉功能和再生,验证了所提出方法的有效性。