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International Journal of Bioprinting 3D bioprinting for musculoskeletal system

for VML are limited. The most common procedure is functional features of natural skeletal muscle. Kim et al.
muscle flap transplantation, which involves the transfer fabricated human skeletal muscle constructs that were
of autologous tissue with blood and nerve supply from integrated with neural cells via bioprinting and evaluated
the donor site to the injured site in the patient. Despite the effects of neural input on the bioprinted constructs.
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some beneficial outcomes, this treatment suffers from the The results showed that the neural-skeletal muscle
common drawbacks of autologous tissue transplantation, constructs achieved rapid integration with the host neural
such as donor tissue deficiency, donor site morbidity, and network and enhanced the recovery of muscle function.
potential graft failure. 120,121 Another treatment option is 3D-bioprinted constructs have mechanical properties
physical therapy, which compensates for the functional that are similar to native tissue, which is especially
deficits associated with VML defects by hypertrophy of important for musculoskeletal tissue regeneration. A
the remaining muscles. However, this treatment is not new bioprinting strategy, assembled cell-decorated
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suitable for large-scale VML defects, and VML patients are collagen (AC-DC) bioprinting, was invented to fabricate
often unable to perform physical exercise, limiting its use musculoskeletal tissue implants for the reconstruction of
in clinic. These concerns have led to the investigation of damaged tissues. The mechanical properties of resultant
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novel regenerative medicine treatments. implants consisting of robust glyoxal crosslinked collagen
A variety of 3D bioprinting techniques have been microfibers and human-related cells were comparable
investigated in order to create skeletal muscle grafts with to or better than those of native tissue, and they could
regenerative potential for VML repair (Table 3). Choi et al. facilitate function restoration.
developed a granule-based printing reservoir to fabricate Muscle fiber bundles fuse to form skeletal muscle with a
volumetric muscle constructs based on cell-laden dECM highly parallel-aligned structure that is essential for effective
bioinks. The resultant constructs supported high cell force transfer and anisotropic locomotion. 140-142 Therefore,
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viability and enhanced muscle formation to promote the fabrication of biomimetic muscle constructs to simulate
muscle regeneration. Behre et al. prepared patient-specific the aligned structure, which can stimulate 3D cell alignment,
scaffolds for VML repair using ECM-based bioinks. is crucial for skeletal muscle tissue regeneration. Numerous
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This fabrication process was implemented with the attempts have been made in muscle cell alignment by
freeform reversible embedding of suspended hydrogels improving the bioprinting strategies. 28,128,136 Li et al.
(FRESH) 3D bioprinting technology, which allows the developed bioinks based on viscoelastic hydrogels, which
ECM hydrogel to match the tissue defects and manage enhanced the arrangement of the cell microenvironment.
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the characteristics of the construct microstructure. The Combined with the gel-in-gel strategy, the bioprinted
creation of anisotropic muscle tissues remains a challenge biomimetic scaffold with aligned structure was prepared
for traditional 3D extrusion bioprinting. In combination for VML repair. The scaffold demonstrated the capacity
with the ice-templating method, Luo et al. developed an to induce the alignment and elongation of 3D myoblasts.
innovative bioprinting technology, namely vertical 3D Distler et al. demonstrated that the microstructure of
extrusion cryo-bioprinting. With precise temperature the hydrogel could be oriented by adjusting printing
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control, GelMA-based bioinks can be bioprinted into conditions, such as nozzle diameter and extrusion pressure,
freestanding filamentous constructs with interconnected, thus guiding the orientation of cell growth. During the
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anisotropic, and gradient microchannels. Using this 3D printing process, the orientation of C2C12 cells in the
technology, the printed muscle-tendon units showed printing direction increased with the rise of the shear force
high cell survival and desired cell arrangement. Without in the printing head. Kim et al. described an innovative
using the toxic materials, Mostafavi et al. developed bioprinting strategy for the guidance of the muscle cells.
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GelMA-based foam bioinks for the preparation of To induce the alignment of laden myoblasts, they designed
tissue engineering scaffolds. Homogeneous and collagen-based bioinks mixed with gold nanowires, which
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interconnected pores were generated by mechanical provided aligned topological clues to the cells in response
stirring of the precursor gel solution at a high rate, to the external electric field (Figure 3B and C). The bioink
which facilitated cell infiltration and spreading in the supported high cell viability, and the printed structures
hydrogels. The porous bioinks were compatible with demonstrated excellent myoblast alignment and efficient
both conventional and handheld bioprinters (Figure myotube formation. Yeo et al. described a novel bioprinting
3A). Moreover, the constructs bioprinted based on the method in combination with the electrohydrodynamic-
bioinks presented significant regenerative potential direct-writing (EHD-DW) procedure, which enabled the
as evidenced by a mouse VML model. Successful biofabrication of high-resolution microscale structures.
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biofabrication of skeletal muscle constructs for VML Alginate/fibrin bioinks loaded with myoblasts or
repair requires precisely replicating the structural and endothelial cells can be printed into spatially patterned

Volume 10 Issue 1 (2024) 85 https://doi.org/10.36922/ijb.1037