Magnetic Nanocomposite Hydrogels for Tissue Engineering: Design Concepts and Remote Actuation Strategies to Control Cell Fate

Abstract

Most tissues of the human body are characterized by highly anisotropic physical properties and biological organization. Hydrogels have been proposed as scaffolding materials to construct artificial tissues due to their water-rich composition, biocompatibility, and tunable properties. However, unmodified hydrogels are typically composed of randomly oriented polymer networks, resulting in homogeneous structures with isotropic properties different from those observed in biological systems. Magnetic materials have been proposed as potential agents to provide hydrogels with the anisotropy required for their use on tissue engineering. Moreover, the intrinsic properties of magnetic nanoparticles enable their use as magnetomechanic remote actuators to control the behavior of the cells encapsulated within the hydrogels under the application of external magnetic fields. In this review, we combine a detailed summary of the main strategies to prepare magnetic nanoparticles showing controlled properties with an analysis of the different approaches available to their incorporation into hydrogels. The application of magnetically responsive nanocomposite hydrogels in the engineering of different tissues is also reviewed.

Engineering next-generation bioinks with nanoparticles: moving from reinforcement fillers to multifunctional nanoelements

“…67,68 Therefore, the incorporation of anisotropic fillers can be leveraged for supporting not only the printing process but also to promote cell alignment required to recreate anisotropic tissues such as tendon, muscle, cartilage, and their interfaces. 12,21 Other types of nanofillers have also been evaluated to provide bioinks with enhanced mineralization functionality. For instance, the addition of strontium-carbonate NPs has been demonstrated as an efficient strategy to increase the printability and the mineralization degree of GelMA-based hydrogels, thus inducing the osteogenic differentiation of the MSCs encapsulated within the nanocomposite 3D bioprinted constructs.…”

“…[77][78][79][80] On the other hand, magnetic materials have been used to provide nanocomposite hydrogels with anisotropic structure and magnetomechanic stimulation properties through the application of external magnetic fields. 12 The intrinsic properties of magnetic nanoparticles (MNPs) allow control over their distribution within the 3D space of hydrogel networks by applying magnetic radiations, opening the possibility to the design of anisotropic magneticallyresponsive constructs. 12 MNPs with superparamagnetic behavior are especially appealing for this purpose since in this regime, the particles do not retain any magnetization energy after the application of an external magnetic field, which precludes the formation of aggregates and allows full control over their magnetic guidance/distribution.…”

“…12 The intrinsic properties of magnetic nanoparticles (MNPs) allow control over their distribution within the 3D space of hydrogel networks by applying magnetic radiations, opening the possibility to the design of anisotropic magneticallyresponsive constructs. 12 MNPs with superparamagnetic behavior are especially appealing for this purpose since in this regime, the particles do not retain any magnetization energy after the application of an external magnetic field, which precludes the formation of aggregates and allows full control over their magnetic guidance/distribution. 81,82 The incorporation of nanofillers to render light-responsive hydrogels has also been explored, being graphite-graphene oxide structures among the most commonly utilized for this fabrication strategy.…”

“…In this sense, printable hydrogels can be modified with nanoparticles (NPs) and/or biological factors, among others, for the biofabrication of 3D constructs that seek to replicate the main characteristics and properties of native tissues. [12][13][14][15] In pioneering works that have used such strategy, the addition of nanofillers was shown to allow tuning the physical characteristics of the bioinks, such as viscosity, stiffness, and nonlinear viscoelasticity (shear-thinning behavior), in order to improve their printability. 16,17 In general, the mechanical properties of hydrogels proportionally improve with nanofillers concentration, but the incorporation of these nanostructures can, on the other hand, have either positive or negative affects over the printing fidelity of the constructs, depending on the type of filler and its concentration.…”

Improving the mechanical performance of P(N‐hydroxymethyl acrylamide/acrylic acid/2‐acrylamido‐2‐methylpropanesulfonic acid) hydrogel via hydrophobic modified nanosilica

“…Commonly, hydrogels are fabricated from natural polymers such as gelatin, collagen, chitosan, hyaluronic acid, or from synthetic polymers such as poly(ethylene glycol), poly(glycolic acid), or poly(vinyl alcohol) 4 . Hydrogels are widely used in various fields, including sewage treatment, 5,6 artificial intelligences, 7,8 drug delivery, 9,10 tissue engineering, 11,12 wound dressing, 13 and so forth. In many industrial applications, the hydrogels need higher mechanical properties.…”