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International Journal of Bioprinting Magnetic (Bio)inks for tissue engineering

for inks that may or not contain cells. An overview on hydrogels should be biocompatible and present adequate
selected recent studies exploring approaches for 3D (bio) bioactive cues, mechanical properties, and degradation
printing of magnetic hydrogels is provided. profiles that mimic those of the target tissue according
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to whether the construct is supposed to replace the tissue
4.1. 3D extrusion bioprinting or support the regeneration process. Several examples of
3D (bio)printing is a technique that allows the hydrogels fabricated using 3D (bio)printing and of other
manufacturing of 3D, well-organized structures by types of constructs obtained through this manufacturing
applying layer-by-layer precise positioning of biomaterials, process are summarized in Table 3 and Figure 3.
biomolecules (e.g., growth factors ), and/or cells. This
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technique allows fabrication of constructs with different 4.2.1. Cartilage tissue engineering
biological and mechanical biomimicking features naturally Magnetic hydrogels are applied to cartilage tissue
found in the target tissue, with potential applications in engineering strategies. Magnetic nanoparticles can
tissue engineering, drug delivery, or in the development increase the chondrogenic differentiation potential of cells
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of organs on chips for disease modeling and drug through various mechanisms, namely upon internalization
screening. In this review, special attention is given to by the cells, by binding to their surface or serving as
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extrusion, the technique most predominantly reported a guide for their migration and condensation in one
to 3D (bio)printing of magnetic hydrogels. Additional single location, which is crucial in cartilage formation.
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information on inkjet and laser assisted-bioprinting However, the application of these hydrogels in this
methods can be found elsewhere. 49,52-54 field is very challenging given that cartilage tissue has a
3D extrusion bioprinting relies on pushing a bioink through highly complex structure, and the proper combination of
a syringe by either pneumatic or mechanical methods, to specific biochemical/physical cues is required to achieve
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produce a filament which is placed, layer by layer, in a specific functional tissue substitutes. Indeed, a method to produce
shape, according to a model designed using computer-aided such cartilage substitute with native-like extracellular
design (CAD) software. The bioink is composed by one or matrix composition and adequate mechanical properties
more biomaterial, cells, and, potentially, other biomolecules has not yet been developed. 3D (bio)printing of magnetic
to aid in cell function and/or proliferation. These must be hydrogels has the potential to construct a structure that
biocompatible and have mechanical, rheological, chemical, more closely resembles the native cartilaginous tissue by
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and biological characteristics that allow to produce a final accurately mimicking its natural architecture, which can
structure that resembles the tissue mechanics and structure, then be combined with an external magnetic stimulation
with high shape fidelity to the intended design and low batch- to further stimulate the scaffold’s microenvironment in a
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to-batch variation. 55 remote and non-invasive manner.
The main advantages of extrusion bioprinting, when In an attempt to mimic this specific microenvironment,
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compared to other advanced manufacturing techniques, Betsch et al. explored the insertion of time as a fourth
are its affordability and its ability to print bioinks with dimension in the bioprinting process of magnetic hydrogels
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high cell densities and to extrude more viscous solutions, aiming to generate two-layered constructs, each with a
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which allow for a diverse array of materials to be used in different fiber arrangement (aligned or random), built
bioinks formulation. While cell viability can be affected sequentially according to a time-dependent orientation of
by the high shear stresses the cells are subjected to, 3D the magnetic field. To achieve this goal, the authors used an
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extrusion bioprinting has been studied in several areas of agarose and type I collagen blend with streptavidin-coated
tissue engineering. 3,6,8,22,23,58 iron nanoparticles to improve the particles’ attachment
to the collagen fiber network. The results showed that the
4.2. Applications of 3D (bio)printed magnetic collagen fibers, within the scaffold, are aligned in parallel
hydrogels to the magnetic field due to the movement of the particles.
3D (bio)printing of magnetic hydrogels experienced Furthermore, the alignment of the fibers led to an increase
a growing interest for the manufacturing of smart in the compression moduli of the scaffolds. Human knee
and structure-defined scaffolds for tissue engineering articular chondrocytes were seeded on the two-layered
applications. Magnetically-responsive materials used scaffolds, one layer with horizontally aligned fibers and
for this purpose need to be compatible with the printing the other with randomly oriented fibers, mimicking the
process, namely in terms of rheological properties, gelation superficial and middle layers of articular cartilage tissue,
kinetics, and crosslinking nature. Furthermore, printing respectively. The results showed that the scaffolds were
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parameters such as printing resolution and shape fidelity cytocompatible, and the expression of collagens I and II
also affect the final characteristics of the hydrogels. These by the cells cultivated on the two-layered scaffolds was

Volume 10 Issue 1 (2024) 8 https://doi.org/10.36922/ijb.0965