How do the Local Physical, Biochemical, and Mechanical Properties of an Injectable Synthetic Anisotropic Hydrogel Affect Oriented Nerve Growth?

Abstract

As an injectable tissue regenerative platform, Anisogel aims to recapitulate the complex and anisotropic architecture of native extracellular matrix by the use of magneto‐responsive microgels, which are oriented under a low magnetic field of ≈100 mT, while a surrounding hydrogel matrix cross‐links around them. This system promotes the oriented growth of neurons when cultured in vitro. In this study, how the local microgel properties affect neurite outgrowth and orientation is aimed to understand using dorsal root ganglia from chicken embryos. When the surrounding matrix is a synthetic poly(ethylene glycol) hydrogel, the microgel concentration and length required to achieve oriented nerve growth is higher compared to fibrin‐based Anisogels. Microgels should be stiffer than the matrix for cells to sense the mechanical anisotropy but a wide range of microgel stiffness leads to similar cell alignment and growth. On the other hand, modification of the microgels with common extracellular matrix molecules enhances nerve growth but deteriorates nerve alignment compared to bioinert microgels in a cell adhesive surrounding gel. Finally, covalently coupling these microgels to the surrounding matrix reduces both cellular orientation and outgrowth suggesting a reduction in the ability of cells to sense the anisotropy.

Cell Development Enhanced Bionic Silk Hydrogel on Remodeling Immune Pathogenesis of Spinal Cord Injury via M2 Polarization of Microglial

“…The mechanical properties of substrates have been demonstrated to be important regulators on cell behavior. [21,25] Recent findings have implicated that neural stem cells preferentially differentiate into neurons on soft materials (G′ < 1 kPa). [39] Therefore, the mechanical properties and gelation efficiency of the hydrogels were investigated via rheological analysis.…”

“…[ 19 ] Biomaterial scaffolds with tunable mechanical properties and bionic structures have been reported to facilitate cell adhesion/differentiation and neurite regrowth for accelerating nerve repair. [ 20–24 ] Particularly, softer biomaterials encourage neuronal differentiation of NPCs and enable axon regrowth, whereas stiffer biomaterials encourage NPCs to differentiate into astrocytes. [ 25 ] Meanwhile, scaffolds modified with extracellular matrix (ECM)‐mimicking molecules, such as RGD (Arg‐Gly‐Asp) peptides, can provide enhanced cell adhesion cues to facilitate cell attachment and axonal regrowth, and promote anti‐inflammatory M2 macrophage polarization by activating 𝛼 v 𝛽 3 integrin.…”

Magnetic hydrogels with ordered structure for biomedical applications

“…Different from hydrogels without oriented structure, those ordered hydrogels were able to guide the growth and extension of fibroblasts and nerve cells, providing a minimal invasive route for complex tissues regeneration. In a recent research, the types of hydrogel matrix and its stiffness, and surface biomodifications were also proved to affect the cell responses ( Babu et al, 2022 ). Micro hydrogel with small size is another method to realize minimal invasion and remote control.…”

Magnetically Actuable Complex‐Shaped Microgels for Spatio‐Temporal Flow Control

“…[ 29 ] The magnetic nanoparticles are usually dispersed in the reaction mixture and integrated during the polymerization of the hydrogels. [ 20,21,25 ] Magnetic microgel rods loaded with SPIONs fabricated via PRINT were found to align exclusively along the magnetic field as a consequence of their shape anisotropy. [ 22 ] To pre‐program the magnetic response and pre‐define the magnetic moment of the microgels, only a few studies have explored the possibility of fabricating anisometric microgels under the presence of an external magnetic field.…”

“…As an example, the magnetic response of rod-shaped microgels can be used to remotely control their orientation during the scaffold build-up to guide cell growth. [20] Besides allowing to control the structural assembly, [21][22][23] magnetic responsive building blocks are ultimately expected to provide the possibility to study mechanotransduction similar to light-responsive soft hydrogels. [24] Several examples of the incorporation of magnetic materials into hydrogels and microgels by various fabrication methods are reported in the literature.…”