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International Journal of Bioprinting                                3D bioprinting for musculoskeletal system




            3.5. IVD                                           to electrospinning, 3D printing allows customization of
            Located between adjacent vertebrae, IVD consists of three   the scaffold without additional assembly steps. Bhunia
            elements: nucleus pulposus (NP), annulus fibrosus (AF),   et al. fabricated an engineered AF scaffold based on silk
            and cartilaginous endplate. It is a complex fibrocartilaginous   fibroin (SF) and carrageenan by 3D printing technology.
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            structure that absorbs and transfers mechanical load from   The scaffold simulated the multilamellar structure of the
            various directions and allows flexible movement of the   native AF and showed good mechanical properties. In
            spine.  IVD is prone to degradation and has poor self-  addition, the scaffold supported cell growth and promoted
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            healing ability due to its avascularity.  IVD degeneration   the production of AF-specific ECM.  The accuracy of
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            (IVDD) is a pathological process characterized by disorder   printing is an important factor affecting the structure
            of ECM structure, loss of proteoglycan, herniation of NP,   and function of 3D-printed scaffolds. Liu et al. used the
            and loss of disc height. The etiology of IVDD is complex   electrohydrodynamic 3D printing technique to prepare
            and involves many pathogenic  factors, such as trauma,   an AF scaffold with high resolution for IVD regeneration
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            aging, spinal deformities, and genetic factors.  As the   (Figure 5).  After finite element analysis, the design of the
            most common cause of low back pain, IVDD results in a   structure was optimized before printing. The implanted
            large number of patients with disability. Every year, more   scaffold maintained the height of the disc and promoted
            than 500 million people worldwide suffer from low back   the partial recovery of the biomechanical function of IVD.
            pain, imposing tremendous socioeconomic burden on   Hu  et al. developed a bioink composed of gellan gum
            humans . The current treatment for IVDD includes   and PEGDA for the bioprinting of IVD in combination
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            conservative treatments and surgical treatments. The former   with poly(lactic acid) (PLA).  The bioprinted construct
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            includes steroid injections, nonsteroidal anti-inflammatory   exhibited excellent mechanical properties and supported
            drugs, and physiotherapy, and the latter includes spinal   high cell viability. Although bioprinted tissue constructs
            fusion, total IVD replacement, and discectomy. These   have shown promising results in musculoskeletal tissue
            interventions can relieve symptoms; however, none of   engineering, 3D bioprinting of IVD is still rudimentary.
            them has been successful in reversing IVDD progression
            and restoring disc function. Moreover, some treatments,   4. 3D bioprinting for disease modeling
            such as spinal fusion, can alter the biomechanics of the   For  a  long  time,  preclinical  drug  screening  mainly
            spine, leading to an increased risk of degeneration of   relies on the use of animal models.  As an alternative to
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            adjacent discs.  Hence, novel intervention measures that   human disease research, animal models offer a controlled
            can effectively slow down the degeneration process and   experimental system, which maintains the overall
            regenerate degenerated IVD are urgently needed.    complexity of cells, tissues, and other factors within
               Several studies have attempted to use tissue    organ systems. However, biomedical results of animal
            engineering for IVD regeneration but have encountered   models often do not fully represent the actual status of
            many challenges. 172-174  Among them, the preparation of   human diseases due to the vast genetic, phenotypic, and
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            engineered scaffolds is a tricky problem because of the   physiological differences between animals and humans.
            complex microstructure of IVD, especially the AF. Accurate   Even by means of genetically engineered animal models, it
            simulation of biomimetic AF anatomical structure is   is difficult to simulate the critical biological characteristics
            the key to the function restoration of IVD. This relies on   of diseased cells and their microenvironment, diseased
            advanced scaffold preparation methods. Electrospinning   tissues or organs, or their physiology in patients. Moreover,
            is a widely used technique for the preparation of fibers,   ethical concerns must be taken into account when carrying
            which can be several microns or even nanometers in   out animal experiments.  These limitations impede the
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            diameter. Electrospun nanofibers are considered excellent   translation of results from animal experiments into human
            engineered materials due to their good biocompatibility,   treatments.  Another approach for drug validation is 2D
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            controllable  mechanical  properties,  and  similar  culture of human cells that provides valuable insights into
            characteristics to natural ECM. To mimic the hydrophilic   pathological mechanisms in a more controlled manner. This
            environment and hierarchical structure of native AF, Yang   approach has the advantages of ease of use, low cost, and
            et al. used electrospinning technology to prepare a scaffold   potentially high throughput, thus enabling the testing of
            consisting of PCL, poly(lactic-co-glycolic acid) (PLGA)   multiple conditions and treatments in a short time. Despite
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            and type I collagen.  In vivo experiments showed that the   these advantages, 2D cultured cells are obviously deficient
            scaffold achieved good integration with the surrounding   in complex 3D structures and interactions found in vivo,
            host tissues and promoted the recovery of disc function. In   which are essential for maintaining proper functional
            recent years, 3D printing technology has risen in popularity   phenotypes in the musculoskeletal system. Shortcomings
            and has been used in IVD tissue engineering. In contrast   in existing drug screening strategies have led to a growing

            Volume 10 Issue 1 (2024)                        91                          https://doi.org/10.36922/ijb.1037
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