Magnetically-driven 2D cells organization on superparamagnetic micromagnets fabricated by laser direct writing

I A Paun,C C Mustaciosu,B S Calin,M Mihailescu,A M Sandu

doi:10.1038/s41598-020-73414-4

Abstract

We demonstrate a proof of concept for magnetically-driven 2D cells organization on superparamagnetic micromagnets fabricated by laser direct writing via two photon polymerization (LDW via TPP) of a photopolymerizable superparamagnetic composite. The composite consisted of a commercially available, biocompatible photopolymer (Ormocore) mixed with 4 mg/mL superparamagnetic nanoparticles (MNPs). The micromagnets were designed in the shape of squares with 70 µm lateral dimension. To minimize the role of topographical cues on the cellular attachment, we fabricated 2D microarrays similar with a chessboard: the superparamagnetic micromagnets alternated with non-magnetic areas of identical shape and lateral size as the micromagnets, made from Ormocore by LDW via TPP. The height difference between the superparamagnetic and non-magnetic areas was of ~ 6 µm. In the absence of a static magnetic field, MNPs-free fibroblasts attached uniformly on the entire 2D microarray, with no preference for the superparamagnetic or non-magnetic areas. Under a static magnetic field of 1.3 T, the fibroblasts attached exclusively on the superparamagnetic micromagnets, resulting a precise 2D cell organization on the chessboard-like microarray. The described method has significant potential for fabricating biocompatible micromagnets with well-defined geometries for building skin grafts adapted for optimum tissue integration, starting from single cell manipulation up to the engineering of whole tissues.

Highlights

We demonstrate a proof of concept for magnetically-driven 2D cells organization on superparamagnetic micromagnets fabricated by laser direct writing via two photon polymerization (LDW via TPP) of a photopolymerizable superparamagnetic composite
One of the important aspects concerning the use of micromagnets to guide the cells behavior is their size and positioning[25]: the thickness has to be as low as possible to reduce the physical damages of the cells, the lateral dimensions determines the lateral magnetic effective range of the micromagnets, while the spatial periodicity is important for the spatial distribution of the seeded cells
By taking advantage of the versatility of the structures that can be fabricated by LDW via TPP, we produced 2D microarrays of squared superparamagnetic microstructures less than 10 μm in height compared with the surroundings and having the lateral dimension of 70 μm, which is very close of a standard dimension of a fibroblast cell

Summary

Introduction

We demonstrate a proof of concept for magnetically-driven 2D cells organization on superparamagnetic micromagnets fabricated by laser direct writing via two photon polymerization (LDW via TPP) of a photopolymerizable superparamagnetic composite. Under a static magnetic field of 1.3 T, the fibroblasts attached exclusively on the superparamagnetic micromagnets, resulting a precise 2D cell organization on the chessboardlike microarray. Nd-based micromagnets were fabricated by patterning Si pillars using lithography and deep reactive ion etching, followed by high rate triode sputtering of Ta/NdFeB/Ta trilayers that were uniformly coated with a parylene layer for b iocompatibility[10]. Another issue is that, for achieving magnetic trapping of cells, the dimensions of the magnets should range from millimeter down to micrometric range[28]. An additional drawback is that, for being moved using external magnets, the cells first have to be magnetized by the internalization of MNPs, which raises problems related to nanoparticles toxicity and r emoval[29]

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Conclusion