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International Journal of Bioprinting                          Hybrid biofabrication of neurosecretory structures


            1. Introduction                                    secretory  function  after  transplantation  in  mice .  Yu  et
                                                                                                      [22]
                                                               al. used parathyroid tissue and adipose-derived acellular
            Neuroendocrine organs play an important role in    extracellular matrix bioink to print  a pre-designed
            maintaining the survival of the human body, regulating the   polycaprolactone (PCL) grid . The results of  in vivo
                                                                                       [23]
            balance of the environment, protecting human tissue from   transplantation in rats showed that parathyroid tissue could
            emergency responses, and avoiding external infection .   maintain its activity for 4 weeks and exhibited the function of
                                                        [1]
            Major brain trauma, vascular diseases, tumors, and other   secreting parathyroid hormone. Zubizarreta et al. printed a
            insults  can  lead  to  loss of  function of  neurosecretory   model of the female reproductive system in vitro through 3D
            organs, which leaves patients prone to infection, hormone   bioprinting . Because many endogenous and exogenous
                                                                        [24]
            imbalance, systemic complications, and even death due   factors affect female reproductive health and fertility, its
            to low hormones . Even partial removal of endocrine   function is to provide hormonal support and an anatomical
                          [2]
            organs  can  cause  loss  of  endocrine  function,  which   structure for the production of new offspring. Diao  et al.
            often necessitates long-term additional hormone drug   established a growth hormone pituitary adenoma model
            replacement therapy in affected individuals. In addition,   by 3D bioprinting, which showed that pituitary adenoma
            the systemic side effects caused by drugs are new factors   cells presented more active cell cycle progression and had
                                      [3]
            threatening the health of patients .               characteristics of proliferation and invasion of pituitary
                                                                          [25]
              Since the regeneration of endocrine organs remains a huge   adenoma cells . However, there remains a huge demand for
            challenge, biological manufacturing processes have become   3D bioprinting of neurosecretory structures with secretory
            a viable option in this regard. The manufactured endocrine   function for development and translational purposes.
            organs not only require new biological manufacturing   A single manufacturing technology often has inherent
            technologies for the implementation and maintenance of   defects in the manufacture of complex organs with special
            better organ characteristics, but also needs to be long-term   needs. However, hybrid biofabrication, which involves various
            and safe in nature as well as have a stable structure and   complementary biological manufacturing technologies,
            effective secretory function . Recently, as a new biological   avoids the defects of a single manufacturing technology and
                                 [4]
            manufacturing technology, 3D bioprinting has been gradually   gives full play to their respective advantages, better realizing
            translated into clinical application, which has shown great   the biological manufacturing and functional reconstruction
            potential in overcoming existing clinical challenges . Three-  of  complex  organs [26,27] .  Xu  et al.  used  electrospinning  of
                                                   [5]
            dimensional (3D) bioprinting is based on computer-aided   polycaprolactone fiber and inkjet bioprinting of rabbit
            living cell biomanufacturing technology, including extrusion   elastic chondrocytes suspended in fibrin-collagen hydrogel
            (mechanical and pneumatic) [6,7] , jetting (inkjet, microvalve,   alternately to construct a 3D structure layer-by-layer to
            laser-assisted, and acoustic) [8,9] , and vat polymerization   achieve a cartilage-like tissue formation, cartilage repair, and
            (stereolithography, digital light processing, and two-photon   regeneration in vivo . This method not only addressed the
                                                                              [28]
            polymerization) [10,11] . Irrespective of the type of bioprinting   demand for cartilage strength, but also solved the problem of
            technology, the purpose is to deposit cells, biomaterials, and   matrix microenvironment for the growth of chondrocytes.
            cytokines with high precision and to accurately control the   Hwang et al. developed a hybrid-encapsulated islet system
            spatial geometry, density, and controllable distribution of   based on biological printing technology, which not only
            loaded cells to realize 3D construction of a 3D-bioprinted   protected the growth microenvironment of islet cells from
            structure [12,13] . 3D bioprinting tissues has been reported,   attack by the immune system, but also provided a suitable
            including 3D-bioprinted liver tissue [14-16] , glomerulus ,   matrix environment to maintain the viability, proliferation,
                                                        [17]
            myocardial , brain , and skeletal muscle  and has been   and insulin production of islet cells . Yoon  et al. used
                           [19]
                                             [20]
                    [18]
                                                                                            [29]
            shown to maintain cell bioactivity, tissue morphological   3D-bioprinted hydrogel and electrospun flexible nanofibers
            structure, and organoid function. The tissue-like structures   to create 3D structures alternately, which could better achieve
            produced by the organisms also showed varying degrees of   shape fidelity, maintain structural accuracy, improve the
            biological functions. However, there is little research in the   mechanical properties of compressive strength, modulus,
            field of the biological manufacture of endocrine organs in   and springback limit, and even help open internal channels
            3D bioprinting. Wu et al. constructed a 3D ovarian follicular   for perfusion culture, ultimately generating bioprinted
            microenvironment using a 3D printing system based on   3D structures to maintain stronger biological activity .
                                                                                                           [30]
            gelatin methacryloyl (GelMA) and found that follicles grew   Hybrid biofabrication combined with 3D bioprinting
            and ovulated successfully in scaffolds and that metaphase II   and electrospinning technology avoids the problem of
            oocytes were present after maturation in vitro . Bulanova   insufficient structural strength of a simple hydrogel system
                                                [21]
            et al. used bioprinting technology to construct functional   and could maintain structural stability and better cell activity
            vascularized mouse thyroid structures in vitro and showed   for a longer time. Simultaneously, hybrid biofabrication is


            Volume 9 Issue 2 (2023)                        130                      https://doi.org/10.18063/ijb.v9i2.659
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