Magnetic bioprinting of stem-cell based tissues

Abstract

An attractive approach in cell therapies and medically oriented nanotechnologies is to interface magnetic nanoparticles with cells. This will supply the cells with sufficient magnetization for theranostic applications and for external magnetic field manipulation. In tissue engineering, one challenge is to produce tissue analogues that are large, precisely organized, and responsive to stimuli, preferably without the need for an artificial supporting scaffold. One powerful tool for such biofabrication is certainly the bioprinting technology. In magnetic tissue engineering, it appears possible to use magnetic forces to manipulate cells, both individually and within aggregates, and thereby to produce three-dimensional artificial tissues with inherent capacities for further physical stimulation, a possibility that bioprinting does not offer yet. We here introduce the feasibility of using magnetic forces created by external (micro)magnets to form 3D tissue-like scaffold-free structures. Because stem cells are essential in tissue engineering, such magnetic technologies were developed with magnetized stem cells, and applied for instance to vascular or cartilage tissue engineering. One precondition to this approach, which lies in the magnetization of (stem) cells endowed through internalization of iron oxide magnetic nanoparticles, is to ensure the safety of magnetic nanoparticles with respect to cellular functions, which is initially discussed. Finally, we introduce a magnetic tissue stretcher which, in a single step, allows to create a tissue composed of any type of component cell, then to mature it, stimulate it by compression or stretching at any desired frequency, e.g. cyclically, opening new possibilities in the cardiac muscle tissue engineering field.