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International Journal of Bioprinting 3D bioprinting for musculoskeletal system

control group. Utilizing the swelling properties of gelatin, and limited tissue availability. 144-146 Currently, effective
4D-conceptualized gelatins films with grooves were further treatment options are lacking due to some challenges,
fabricated to bundle the cell-laden GelMA microfibers, including poor blood supply, complex 3D structure
thereby simulating the structure of the native perimysium. with personalized size parameters, deformability, and
Despite these advances, the dynamic changes of aligned unique resistance to tension and compression of the
muscle cells during myotube formation and maturation meniscus. 140,147 Therefore, advanced strategies, including
in large-scale bioprinted construct remain elusive. To this 3D bioprinting for the engineering of fibrocartilage
end, Fan et al. constructed skeletal muscle fiber bundles tissues, are urgently needed. Table 4 presents the recent
with different widths by 3D bioprinting and evaluated the 3D bioprinting studies on meniscus regeneration.
effect of different spatial constraints on the alignment and Meniscus regeneration is severely hampered by a poor
differentiation of muscle cells. The results showed that the match between the implanted scaffolds and the host,
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degree of myotube differentiation was negatively correlated because even the slight adjustments in implant position
with the thickness of the printed muscle bundle. Moreover, can influence contact stress and joint biomechanics. To
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the alignment and maturation of muscle fibers may be address this issue, an anatomically shaped and patient-
affected by the structure width and the forces exerted. It is specific construct was developed via inkjet bioprinting
suggested that physical factors play an indispensable role in for meniscus regeneration (Figure 4). First, MRI data
the generation of skeletal muscle tissue. from a healthy volunteer’s medial meniscus were
3.4. Meniscus obtained to design a STL model. The 3D model was then
The meniscus is a semilunar wedge-shaped fibrocartilage imported into the printer system to guide the subsequent
tissue, which acts a pivotal part in knee locomotion. Its printing process. The bioprinted construct showed good
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primary functions include the distribution and transfer biocompatibility while satisfying shape adaptation.
of mechanical load, shock absorption, joint lubrication, Likewise, Stocco et al. employed an extrusion 3D
and stability. 140,141 The meniscus has a distinctive zonal bioprinter to fabricate a meniscus biomimetic scaffold
organization and structure. The outer region (the red- with compatible anatomical shape using type I collagen
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red zone) is more ligament-like and contains elongated and aligned electrospun nanofibrous mats. The
fibroblast-like cells. This region has predominantly type bioprinting was implemented using a virtual meniscus
I collagen and is equipped with self-healing ability due model created from patient MRI images. The structural
to the presence of blood supply. The inner region, also integrity, shape fidelity, and mechanical strength of
known as the white–white zone, is dominated by round the scaffolds were enhanced by the addition of aligned
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chondrocyte-like cells that are embedded within an ECM nanofibers sheets. In general, hydrogel-based bioinks
rich in type II collagen and glycosaminoglycans (GAGs). alone are too mechanically weak to form self-supporting
This region demonstrates limited regenerative capacity stable constructs. Biocompatible synthetic polymers are
owing to its deficient vascularization. The red–white zone, often used to help maintain the construct’s shape and
a transitional zone with features of both red–red zone improve its mechanical strength. Chae et al. developed
and white–white zone, separates the two zones. Meniscus a biocompatible and functional meniscus construct
lesion is a prevalent orthopedic sports injury that affects using polyurethane_poly(ε-caprolactone) (PU_PCL)
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knee balance and causes pain and joint dysfunction. and a dECM-derived bioink. The ECM components in
Suturing of defects and partial meniscus replacement the bioink provided the embedded cells with a friendly
are often used to repair smaller meniscal tears, which microenvironment for proliferation and differentiation
restore the function of the meniscus to some extent. while PU_PCL imparted robust mechanical properties
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For irreparable meniscal tears, surgical interventions and structural stability to the construct. Jian et al. used
including meniscectomy or meniscus allograft a dual-nozzle printing system and a mixture of PCL and
transplantation are required. The removal of unstable, cell-laden GelMA/MECM bioink to create a biomimetic
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damaged meniscus tissues through partial meniscectomy meniscal scaffold. The scaffold resembled the native
is still the gold-standard surgical intervention of meniscal meniscus in terms of morphology and composition
tears, accounting for half of arthroscopic knee surgeries in and promoted the formation of meniscal tissues in a
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the United States. Nevertheless, meniscectomy disrupts nude mouse model. The organization of cellular and
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the biomechanics of the joint, leading to a dramatically matrix components is essential for musculoskeletal
increased risk of development of knee osteoarthritis tissues to perform their functions. 158,159 For the meniscus,
in the long term. Meniscus allograft transplantation the circumferential organization of collagen fibers and
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also has limitations, such as unfavorable compatibility, cellular components in the outer region enables them to
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inappropriate graft sizing, risk of immunogenicity, withstand hoop stresses. Thus, in addition to replicating

Volume 10 Issue 1 (2024) 88 https://doi.org/10.36922/ijb.1037