Remote Magnetic Nanoparticle Manipulation Enables the Dynamic Patterning of Cardiac Tissues

Abstract

regenerative medicine and remains a major challenge. A multitude of technologies have been described to control the spatial organization of cells in 3D engineered heart constructs including mechanical strain/load [1] and chronic electrical stimulation. [2] Other approaches to guide cellular organization have been reported using microfluidic platforms, [3] light-triggered activation of biomolecules, [4] and 3D bioprinting. [5] However, these techniques often involve elaborate, macroscale stimulation systems and are not always suitable for the fabrication of detailed microarchitectures in vitro as each pattern requires new molds, posts, or frames. [6] The next generation of dynamic systems may be designed to respond to user-defined size and shape triggers for controlling cellular organization on the macroscale without the need for external mechanical supports or material cues. Magnetic procedures to manipulate and remotely control cellular behavior represent a promising approach for fabrication of tissuelike constructs. In particular, magnetic nanoparticles (MNPs) have gained increased attention for use in biomedical applications such as magnetic targeting of stem cells [7] and genes, [8] development of scaffold-free multilayer structures, [9] and spatial patterning of aggregates. [10] Magnetic techniques are advantageous due to their high precision and accuracy. To date, magnetic fabrication of biological structures has been illustrated by the assembly of biomembranes made of organized yeast, [11] the formation of "artificial retinas" by magnetic field modulation of chiromagnetic nanoparticles, [12] or the engineering of vocal folds, [13] among others.Here, we report a new platform for engineering tissue morphologies with controlled geometries. Specifically, we used magnetic fields to direct the assembly and patterning of magnetized human cardiomyocytes (CMs) labeled with MNPs in collagenbased hydrogels. Our system enables dynamic manipulation of cells within 3D biomaterials that can be applied to engineer patterned tissues to investigate cellular and tissue behavior. Furthermore, the simplicity and the faithful reproduction of our approach will enable the creation of customized 3D constructs with a new range of complementary implementations such as in biomedical devices, soft robotics, and flexible electronics.First, we designed functionalized MNPs to target and label human induced pluripotent-stem-cell-derived cardiomyocytes (hiPSC-CMs, Figure 1a). For that purpose, we conjugated an antisignal-regulatory protein alpha (SIRPA) cell surface mono clonal antibody [14] labeled with a fluorophore to three types of MNPsThe ability to manipulate cellular organization within soft materials has important potential in biomedicine and regenerative medicine; however, it often requires complex fabrication procedures. Here, a simple, cost-effective, and one-step approach that enables the control of cell orientation within 3D collagen hydrogels is developed to dynamically create various tailored microstructures of cardiac...

Independent Tuning of Nano‐Ligand Frequency and Sequences Regulates the Adhesion and Differentiation of Stem Cells

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Assembly of Multi‐Spheroid Cellular Architectures by Programmable Droplet Merging

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Nanomaterials for Cardiac Tissue Engineering

“…In one such study, magnetic ferumoxytol nanoparticles were used to label cardiosphere-derived stem cells and to target them into coronary arteries of rat post-myocardial infarction ischemia/reperfusion models, thereby addressing the ordinarily low level of stem cell retention and engraftment [100]. In another study, magnetic iron oxide nanoparticles have also been utilized in guiding tissue scaffold structure following implantation into a rat model [101]. In this study, Zwi-Dantsis et al demonstrated that magnetic iron oxide nanoparticles conjugated to antibodies directed at signal-regulatory protein alpha (SIRPA) could be utilized to manipulate human cardiomyocytes in situ with magnets.…”