Tissue regeneration of sensitive tissues calls for injectable scaffolds, which are minimally invasive and offer minimal damage to the native tissues. However, most of these systems are inherently isotropic and do not mimic the complex hierarchically ordered nature of the native extracellular matrices. This review focuses on the different approaches developed in the past decade to bring in some form of anisotropy to the conventional injectable tissue regenerative matrices. These approaches include introduction of macroporosity, in vivo pattering to present biomolecules in a spatially and temporally controlled manner, availability of aligned domains by means of self-assembly or oriented injectable components, and in vivo bioprinting to obtain structures with features of high resolution that resembles native tissues. Toward the end of the review, different techniques to produce building blocks for the fabrication of heterogeneous injectable scaffolds are discussed. The advantages and shortcomings of each approach are discussed in detail with ideas to improve the functionality and versatility of the building blocks.

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.

Micron‐scale anisometric microgels have received increasing attention to replace macromolecule solutions to create injectable 3D regenerative hydrogels. Interlinking these rod‐shaped microgels results in microporous constructs, while incorporating magnetic nanoparticles inside the microgels enables their alignment to introduce directionality. This report demonstrates that the angle of microgel alignment in a static external magnetic field can be pre‐programmed, broadening their applicability to artificially assemble into specific architectures. The magnetic rod‐shaped polyethylene glycol microgels are prepared via in mold polymerization. Ellipsoidal maghemite nanoparticles, integrated as responsive fillers are pre‐aligned either parallel or orthogonal to the long axis of the microgel with a weak magnetic field during rod fabrication to implement additional control over their magnetic orientation and allow their precise manipulation and actuation. The magnetic response of the microgels to static and rotating magnetic fields is discussed depending on various process and design parameters, such as magnetic field strength, angular frequency, and pre‐alignment. Finally, the applicability of the approach for tissue engineering is highlighted by growing mouse fibroblasts in three dimensions within Anisogels, i. e., hydrogels containing a mixture of rods with both a parallel and orthogonal orientation, marking a new step toward more advanced functional cell templating for tissue engineering.