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International Journal of Bioprinting 3D bioprinting for musculoskeletal system

Pluronic F127 is most commonly used in 3D bioprinting. activities including mineral transfer, hematopoiesis,
Pluronic F127 solution can flow at low temperature (<10°C), and hormone modulation. The cell types of bone tissue
which is conducive to cell encapsulation and dispersion. As include bone progenitor cells, osteoblasts, osteocytes, and
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the temperature rises, the solution gradually transitions to a osteoclasts, which are responsible for regulating the process
gel state by self-assembly. Due to its inverse thermogelling of bone formation and resorption. Despite the remarkable
properties, Pluronic F127 gained much attention in the field regenerative capacity of bone tissue, significant challenges
of 3D bioprinting. Mozetic et al. developed a thermosensitive remain when it comes to repairing large segmental bone
bioink based on Pluronic/alginate blends and investigated its defects caused by various factors, such as tumor resection,
effect on the behaviors of C2C12 cells. This system enables infections, or trauma. 47,48 Clinicians often have to resort to
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printing of cell-laden structures with good shape retention surgical intervention in cases where significant bone defects
under physiological conditions. Shearing forces generated need to be repaired, with autografts, allografts, xenografts,
during the printing process induced cellular alignment and inorganic grafts being the most commonly used
along the deposition direction. The resulting constructs approaches for repairing bone defects. 49,50 However, existing
demonstrated high cell viability and enhanced myogenic gene clinical treatments for bone repair suffer from several
expression. Polyethylene glycol (PEG) is another common shortcomings, such as donor-site morbidity, anatomical
synthetic material used in 3D bioprinting. Polyethylene mismatch, inadequate bone volume, graft absorption, and
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glycol diacrylate (PEGDA), a derivative of PEG, has reactive rejection. To address these limitations, the demand for
acrylate groups at both ends and can be used to prepare tissue-engineered bone substitutes has been on the rise,
hydrogels by photocuring. A study has demonstrated that leading to the development of new, converging technologies
the mechanical performance of bioprinted constructs can that offer hope for more effective and sustainable bone repair
be flexibly adjusted by altering the concentration of PEGDA solutions. As a cutting-edge technology, 3D bioprinting has
in bioinks. As a synthetic polyether, PEO is broadly used been widely used in the field of bone regeneration due to
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in the field of 3D bioprinting owing to its biocompatibility, its significant potential to create functional bone grafts
inertness, and ease of molecular modification. Several (Table 1). For example, recent advances in 3D bioprinting
studies have demonstrated that the addition of PEO can have enabled the development of multicell co-culture
enhance the strength of hydrogen bonding between gelatin models that hold promise for simulating the intricate cellular
chains, leading to phase separation of gelatin/PEO aqueous interactions present in native bone tissue. By constructing
solution. Therefore, PEO often functions as a porogen in the a sophisticated microenvironment, these models provide
bioink system for the generation of micropores in the printed the necessary conditions to investigate and understand the
construct. 45,46 Based on this principle, Ying et al. developed delicate cell–cell interactions that underpin the function
a novel bioink consisting of GelMA and PEO and induced of bone tissue. Tang et al. used GelMA to bioprint a bone
the formation of uniformly dispersed PEO droplets in the construct in which Hertwig’s epithelial root sheath cells
continuous GelMA phase. The printed construct with and dental papilla cells were recombined to mimic the
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highly interconnected pores was generated by removing the microenvironment of cell–cell interaction in vivo. The
PEO phase from the photocrosslinked GelMA hydrogel. formation of the mineralization texture and improved
bone regeneration were observed after implantation of the
3. 3D bioprinting for musculoskeletal construct in an alveolar bone defect model, which may be
attributed to cell–cell interactions (Figure 1).
regeneration
Abbreviations: DFC, dental follicle cell; DPC,
Tissue defects caused by trauma, tumor removal, or dental papilla cell; GelMA: gelatin methacrylate; HERS,
congenital malformations require reconstruction Hertwig’s epithelial root sheath; LAP, lithium phenyl-2, 4,
of anatomy and restoration of function through the 6-trimethylbenzoylphosphinate; UV, ultraviolet.
introduction of custom-made constructs to fill the defects.
Various tissue constructs fabricated by 3D bioprinting Angiogenesis and osteogenesis are considered tightly
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have shown great application potential in the field of coupled during bone development and regeneration.
musculoskeletal tissue engineering. In this section, Vascularization is one of the key factors affecting the
we discuss the recent advances in 3D bioprinting for effectiveness of bioprinted scaffolds for bone regeneration
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musculoskeletal tissue regeneration. in bone tissue engineering. The constructs bioprinted
using stem cells and endothelial cells demonstrated higher
3.1. Bone osteogenic potential than the stem cell constructs. Nulty
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Bone tissue is a hard connective tissue consisting of et al. used fibrin-based bioinks to prepare a prevascularized
cancellous and cortical bone. It not only offers structural construct with customized shapes and sizes. The construct
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support and protection but also sustains various metabolic can significantly promote the formation and development

Volume 10 Issue 1 (2024) 79 https://doi.org/10.36922/ijb.1037