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International Journal of Bioprinting 3D bioprinting for musculoskeletal system

thought to provide more stable structural support for the A common solution is to bioprint the cell-laden porous
growth of viable cells after printing than soft hydrogels. In construct, but its structure is prone to collapse due to the
order to maintain high shape fidelity during cell culture, poor mechanical properties of hydrogels. Especially for the
a minimum stiffness of 10 kPa is required in bioprinted centimeter-scale construct, the internal porous structure
constructs. In addition to meeting the requirements is difficult to maintain effectively. Another solution is
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of cell culture, the bioprinted constructs also need to a synchronous bioprinting strategy that incorporates
withstand the complex mechanical environment faced sacrificial materials. The synergistic interaction between
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by musculoskeletal tissues upon implantation. Such cells and sacrificial biomaterials enhances the printing
strict requirements have led to a shortage of bioinks performance of each component, making it easier to
available for musculoskeletal tissue regeneration. The manufacture complex constructs.
development of new formulation of bioinks is a research Printing vascularized constructs holds the promise
focus in this field. The simultaneous possession of all of overcoming size limitations. Printing individual
the required properties by a single component bioink blood vessels is relatively easy to achieve. However, the
is a challenging task for 3D bioprinting of functional construction of the entire blood vessel network (from
tissues. Researchers are focusing their attention on large-scale to small-scale vessels) is an important issue
multicomponent bioinks, which not only contribute to the to be solved in the field of 3D bioprinting. Brassard et
expansion of biofabrication windows, but also enhance the al. developed a novel organoid printing technology,
functionality and complexity of bioprinted constructs. For BATE, which successfully constructed highly biomimetic
example, a nanoengineered ionic covalent entanglement centimeter-scale tissues, including branch vascular system,
(NICE) bioink was described for the bioprinting of opening up new ways for bioprinting and vascularization
complex and large-scale tissue constructs. Because of of large-sized constructs. The functionalization of
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the unique rheological properties and biological clues of printed constructs is highly dependent on the maturity
the bioink, the encapsulated cells can proliferate stably of the tissue. By altering the physicochemical signals in
and maintain a high survival rate in the bioink. Moreover, the printed construct, cell behaviors can be regulated to
the printed constructs demonstrated good shape fidelity promote tissue maturation. The culture conditions after
and mechanical strength through the synergistic action printing also affect the process of tissue maturation.
of multiple crosslinking mechanisms. The incorporation
of polymer fibers into bioinks can also increase the For clinical use, 3D-bioprinted tissue constructs are
mechanical properties of printed constructs. For example, either surgically implanted in the body after in vitro
the combination of porous PCL fiber meshes and GelMA incubation for maturation or directly generated in tissue
hydrogels loaded with amorphous magnesium phosphate defects by in situ bioprinting. The former strategy requires
significantly improved the mechanical properties of a long time to complete the entire process, which is not
the printed structure and delayed its degradation, conducive to clinical translational application. By means
providing mechanical support for the recruitment and of a robotic manipulator, in situ bioprinting allows for
differentiation of progenitor cells to promote bone tissue the direct construction of functional tissue constructs
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regeneration. In addition to improving the bioink at target locations based on imaging information.
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formulation, the strategy of combining 3D bioprinting To obtain target structures, traditional bioprinting
with 3D-printed scaffold as a support material can methods require direct access to the printing location
significantly improve the mechanical properties of the and allow the printing head to move freely along the x,
entire structure. For example, MSCs-laden fibroin-based y, and z axes. Thus, the current application of in situ
bioinks were bioprinted into 3D-printed PCL frameworks 3D bioprinting is limited to externally exposed damaged
to create constructs with enhanced mechanical properties. areas or sites requiring surgical exposure. Developing
The mechanically reinforced constructs supported robust new 3D printing technologies to expand the application
vascularization and graft mineralization when implanted scope would be a promising solution. Minimally
in vivo. 62 invasive or noninvasive approach is one of the major
trends in clinical treatments. In this context, the concept
The creation and functionalization of large-sized tissue
constructs remains a great challenge in 3D bioprinting. of noninvasive in vivo 3D bioprinting attracts increasing
attention. Based on that, Chen et al. explored near-
The vascular system within the tissue/organ provides the infrared (NIR) light-responsive 3D printing technology
necessary nutrients and allows for metabolic exchange. The to fabricate tissue constructs in vivo in a non-invasive
construction of the nutrient network is necessary when the manner. By modulation and irradiation of NIR, the
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size of the printed tissue construct is greater than 200 µm, injected bioinks can be bioprinted into tissue constructs
which exceeds the diffusion limit of nutrients and oxygen.
with customized patterns. With this approach, living

Volume 10 Issue 1 (2024) 96 https://doi.org/10.36922/ijb.1037