Magnetic force-based cell manipulation for in vitro tissue engineering

Cell manipulation techniques such as those based on three-dimensional (3D) bioprinting and microfluidic systems have recently been developed to reconstruct complex 3D tissue structures in vitro. Compared to these technologies, magnetic force-based cell manipulation is a simpler, scaffold- and label-free method that minimally affects cell viability and can rapidly manipulate cells into 3D tissue constructs. As such, there is increasing interest in leveraging this technology for cell assembly in tissue engineering. Cell manipulation using magnetic forces primarily involves two key approaches. The first method, positive magnetophoresis, uses magnetic nanoparticles (MNPs) which are either attached to the cell surface or integrated within the cell. These MNPs enable the deliberate positioning of cells into designated configurations when an external magnetic field is applied. The second method, known as negative magnetophoresis, manipulates diamagnetic entities, such as cells, in a paramagnetic environment using an external magnetic field. Unlike the first method, this technique does not require the use of MNPs for cell manipulation. Instead, it leverages the magnetic field and the motion of paramagnetic agents like paramagnetic salts (Gadobutrol, MnCl₂, etc.) to propel cells toward the field minimum, resulting in the assembly of cells into the desired geometrical arrangement. In this Review, we will first describe the major approaches used to assemble cells in vitro-3D bioprinting and microfluidics-based platforms-and then discuss the use of magnetic forces for cell manipulation. Finally, we will highlight recent research in which these magnetic force-based approaches have been applied and outline challenges to mature this technology for in vitro tissue engineering.