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International Journal of Bioprinting                                3D bioprinting for musculoskeletal system




               MSDs affect 1.7 billion people and have become the   can effectively replicate desired mechanical characteristics
            leading cause of morbidity worldwide  according to the   and structures. 3D bioprinting allows for the precise and
            Global Burden of Disease Study.  Moreover, the incidence   controlled spatial arrangement of cells in 3D scaffold
                                     1,2
            of MSDs shows an increasing trend with the aging of the   materials. The development of increasingly sophisticated
            population. In the United States, for example, there are   and biomimetic tissue-engineered analogues holds the
            at least 70 million clinic visits and 130 million clinical   promise for producing patient-derived functional grafts as
            contacts for MSDs each year, resulting in more than $150   well as clinically predictive drug testing tools. Therefore,
            billion in the national healthcare system costs.  Mild   it is an emerging strategy of constructing tissues for
                                                     3
            MSDs can be addressed with physical therapy or drug   musculoskeletal regeneration, disease modeling, and drug
            intervention.  Severe  MSDs,  on  the  other  hand,  require   development by 3D bioprinting.
            surgical reconstruction. Autograft represents the gold   In this review, we provide a concise review of 3D
            standard for the treatment of severe MSDs, but is limited   bioprinting,  including  several  common  3D  bioprinting
            by donor site scarcity, morbidity, and pain.  Allografts and   techniques and bioinks. The application of these techniques
                                              4
            xenografts are feasible alternatives, although concerns   in musculoskeletal tissue regeneration is highlighted.
            regarding immunological incompatibility, rejection risk,   Following that, recent advances of 3D bioprinting for
            and infectious agent transmission remain.  Therefore, novel   musculoskeletal disease modeling and drug screening are
                                             5
            approaches to regenerating damaged musculoskeletal
            tissues are urgently needed.                       summarized. Finally, we discuss the existing challenges and
                                                               future perspectives of 3D bioprinting for musculoskeletal
               Tissue engineering enables the creation of viable   regeneration and disease modeling.
            scaffolds for the regeneration of damaged tissues. Since
            the beginning, tissue engineering has the prospect of   2. Brief overview of 3D bioprinting
            generating tissues for a variety of purposes, ranging from
            in  vitro disease modeling to  in  vivo tissue regeneration.   3D bioprinting is the process of patterning and assembling
            Tissue-engineered scaffolds provide a hospitable   bioactive  materials,  such  as  growth  factors,  cells,  and
            microenvironment  for  cell  adhesion,  spreading,  biomaterials based on predefined 3D designs, leading to the
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            proliferation, migration, and differentiation. Moreover, the   creation of a functional tissue construct.  3D bioprinting
            addition of bioactive molecules, such as drugs or growth   technology is a subclass of 3D printing technology that
            factors, can further enhance the ability of scaffolds to   is primarily used in the biomedical field. Traditional 3D
            promote cell differentiation and induce the formation of   printing often uses plastic or alloy materials for printing,
            target tissues. However, generating tissues that precisely   whereas the materials used in 3D bioprinting are called
            mimic  the  structural  and  functional  features  of  native   bioinks, which consist of living cells alone or together with
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            tissues remain unattainable in musculoskeletal tissue   supporting biomaterials such as hydrogels.  The major
            engineering, despite the promising translational potential   advantage of 3D bioprinting over other approaches, such
            of tissue engineering approaches. This is primarily due to   as microengineering and cell sheet engineering, is its
            the fact that conventional manufacturing technologies lack   ability to create spatially complex and heterogeneous tissue
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            the ability to accurately regulate the spatial arrangement of   constructs consisting of cells and/or various biomaterials.
            construction elements.  Furthermore, while spontaneous   Through 3D bioprinting, diverse cells and biomaterials
                              6
            cellular organization processes can build certain types of   can be localized to replicate the structural complexity
            fundamental biostructures, they are extremely difficult to   of tissues. The 3D bioprinting process can be achieved
            regulate and manage. Few technologies have so far been   through different technologies and each technique is based
            able  to  reconstruct  the  complex  tissue  architecture  and   on its own principles and has distinct requirements for the
            cell spatial heterogeneity, which are required to mimic the   materials to be used. Therefore, bioinks and bioprinting
            physiologic function.                              techniques need to be attuned to each other. The following
                                                               is a brief introduction to several common 3D bioprinting
               Recently, three-dimensional (3D) bioprinting is   technologies and bioinks.
            applied  in a variety of biomedical scenes, such as  tissue
            engineering, disease modeling, and drug screening.    2.1. Bioprinting technologies
                                                         7,8
            Compared with traditional tissue engineering approaches,   3D bioprinting technologies create functional tissue
            3D bioprinting has several advantages, such as determining   constructs based on the principles of layer-by-layer
            tissue form prior to printing, and acts as a bridge to clinical   stacking and consistent self-assembly.  According to
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            application. The advancement of 3D bioprinting has   the  adopted  bioprinting  techniques,  these  layers  can  be
            substantially expanded the field of musculoskeletal tissue   integrated by different means, such as heat, light radiation,
            engineering by allowing the development of scaffolds that   and chemical crosslinking. The current mainstream 3D


            Volume 10 Issue 1 (2024)                        76                          https://doi.org/10.36922/ijb.1037
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