Manipulation of cell patterns in three dimensions in a manner that mimics natural tissue organization and function is critical for cell biological studies and likely essential for successfully regenerating tissues--especially cells with high physiological demands, such as those of the heart, liver, lungs, and articular cartilage.(1, 2) In the present study, we report on the feasibility of arranging iron oxide-labeled cells in three-dimensional hydrogels using magnetic fields. By manipulating the strength, shape, and orientation of the magnetic field and using crosslinking gradients in hydrogels, multi-directional cell arrangements can be produced in vitro and even directly in situ. We show that these ferromagnetic particles are nontoxic between 0.1 and 10 mg/mL; certain species of particles can permit or even enhance tissue formation, and these particles can be tracked using magnetic resonance imaging. Taken together, this approach can be adapted for studying basic biological processes in vitro, for general tissue engineering approaches, and for producing organized repair tissues directly in situ.
[Show abstract][Hide abstract] ABSTRACT: The current limitations of regenerative medicine strategies may be overcome through the use of magnetic nanoparticles (MNPs), a class of nanomaterial typically composed of magnetic elements that can be manipulated under the influence of an external magnetic field. Cell engineering approaches following the internalization of these MNPs by cells and/or the incorporation of these nanosystems within 3D constructs (scaffolds or hydrogels) may constitute a new attractive approach to achieve a magnetically responsive system enabling remote control over tissue-engineered constructs in an in vivo scenario. Moreover, the incorporation of bioactive factors within these MNPs also enables a targeted and smart delivery of biomolecules to specific regions and/or triggering specific cell responses upon external magnetic stimulation. Certainly, one of the most attractive properties of MNPs is their ability to be used as theranostic tools for regenerative medicine applications, enabling live monitoring and tracking of the system while simultaneously acting as a therapeutic stimulation.
[Show abstract][Hide abstract] ABSTRACT: Among other biomedical applications, magnetic nanoparticles and liposomes have a vast field of applications in tissue engineering and regenerative medicine. Magnetic nanoparticles and liposomes, when introduced into cells to be cultured, maneuver the cell's positioning by the appropriate use of magnets to create more complex tissue structures than those that are achieved by conventional culture methods.
[Show abstract][Hide abstract] ABSTRACT: Nanomaterials including gold nanoparticles, polymeric nanoparticles, and magnetic iron oxide nanoparticles are utilized in tissue engineering for imaging, drug delivery, and maturation. Prolonged presence of these nanomaterials within biological systems remains a concern due to potential adverse affects on cell viability and phenotype. Accelerating nanomaterial degradation within biological systems is expected to reduce the potential adverse effects in the tissue. Similar to biodegradable polymeric scaffolds, the ideal nanomaterial remains stable for sufficient time to accomplish its desired task, and then rapidly degrades once that task is completed. Here, surface modifications are reported to accelerate iron oxide MNP degradation mediated by polymer encapsulation, in which iodegradable coatings composed of FDA approved polymers with different degradation rates are used: poly(lactide) (PLA) or copolymer poly(lactide-co-glycolide) (PLGA). Results demonstrate that degradation of MNPs can be controlled by varying the content and composition of the polymeric nanoparticles used for MNP encapsulation (PolyMNPs). Incorporated into cellular spheroids, PolyMNPs maintain a high viability compared to non-coated MNPs, and are also useful in magnetically patterning cellular spheroids into fused tissues for tissue engineering applications. Accelerated degradation compared to non-coated MNPs makes PolyMNPs a viable alternative for removing nanomaterials from tissues after accomplishing their desired role.
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