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International Journal of Bioprinting                           Biomechanical mimic-based artificial oviduct system




            1. Introduction                                       Mechanotransduction is a well-defined biomechanical
                                                               process  and  an  important  regulator  of  many  cellular
            Infertility has increased globally since 1978 after the first   processes, such as stem cell differentiation, tumorigenesis,
            baby was born by in vitro fertilization, and the number of   cancer metastasis, cell migration, and cell apoptosis.
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            patients that still require support by assisted reproduction   Biomechanical technologies are currently used for
            techniques (ART) to achieve pregnancy has grown and will   stem cell therapy and cancer therapy without radiation,
            continue to increase.  The success of in vitro fertilization   enhancing tissue regeneration based on biomaterial
                             1
            has improved dramatically with advances such as    stiffness.  Mechanotransduction and biomechanical
                                                                      7,14
            controlled ovarian hyperstimulation, oocyte and embryo   properties of the cellular environment are essential for
            cryopreservation, and intracytoplasmic sperm injection. 2–4   biological activities and affect these processes via physical
            However,  in  ART,  healthy  live  birth  ratios  remain   force.  Biomechanical technologies alter different
                                                                   15
            unsatisfactory for male and female infertility patients.   parameters for cell culture, including stiffness, sheer force,
            Therefore, in reproductive medicine, the development   and  contact  force.   However,  biomechanical  signaling
                                                                              16
            of new technologies  is required to overcome infertility.   under these conditions is incompletely understood and
            Therefore, the present study sought to determine if   is contingent on the type of biomaterials and biophysical
            recapitulating the biomechanical properties of the oviduct   force.  For reproductive cells and systems, such as oocytes
                                                                   17
            could contribute to the success of reproductive medicine. 5–7
                                                               and embryos, optimal biomechanical parameters and
               The oviduct is a complex tube bridging the ovary to   mechanisms of mechanical signaling in response to specific
                                         8,9
            the uterus in mammalian females.  The oviduct has a   forces are incompletely understood and must be elucidated
            tubular structure that supports cellular and molecular   to improve clinical applications.
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            processes necessary for normal fertilization and zygote   3D  bioprinting  allows  the fabrication  of materials
            development to produce a viable embryo. Therefore,   with desired mechanical properties and uses components
            oviduct  fluid  supports  important  biological  factors,   such as  plastic  and  viscoelastic materials.  As  the 3D
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            such as growth factors, hormones, and nutrients, to   structure can be programmed via computer-aided design/
            promote fertilization and preimplantation embryonic   computer-aided manufacturing (CAD/CAM) systems,
            development.  These factors are well-defined and are used   bioprinting can produce complex 3D shapes with high
                       10
            in embryo culture media for in vitro fertilization of human   reproducibility. 20–22  Bioprinting is extensively employed
            oocytes and embryos.  However, oviducts also have   to replicate 3D-functional living tissue, as it enables
                               11
            specific biomechanical properties that support fertilization   the creation of hydrogels that closely mimic  in vivo
                                 6
            and embryo development.  The human oviduct comprises
            three primary longitudinal regions designated from the   conditions, and can be applied to tissues with rigid to soft
                                                                            However, few studies have applied 3D
                                                               properties.
                                                                       21,23,24
            ovary to the uterus: (i) the infundibulum (fimbriae in   bioprinting technologies to reproductive tissue. Previously,
            humans), which comprises primarily ciliated epithelial   Wu et al. used 3D bioprinting to construct an ovarian
            cells; (ii) the ampulla, which contains large numbers of   scaffold with functional ovarian follicle units to mimic
            ciliated epithelial cells and is the site of fertilization; and   the ovaries.  However, research on the oviduct, which
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            (iii) the isthmus, which is abundant in secretory epithelial   is essential to develop a healthy pregnancy, is limited,
            cells.  The  oviduct  transports  gametes  and embryos,   particularly regarding the effects of mechanical culture
                9
            and provides biochemical and biophysical support for   conditions on mechanical stimulation signaling. 26
            preimplantation embryonic development.  In addition,
                                              5–7
            direct and indirect evidence  suggests both physical and   Hydrogels used for 3D bioprinting must mimic the
            molecular interactions among gametes, embryos, and the   tissue  microstructure  and provide  a  suitable  cellular
                                                                              23
            oviduct. Oviduct dysfunction can lead to infertility or   microenvironment.  Hydrogels should also be easy to
            pathophysiological conditions such as ectopic pregnancy   process and possess biological and physical properties
            due to impaired embryo transport. Biomechanical support   that induce necessary cell interactions and responses.
            is necessary to prevent ectopic pregnancy, which occurs due   Gelatin  methacryloyl  (GelMA)  hydrogels  are  commonly
            to impaired embryo transport.  The oviduct also provides   used due to their biocompatibility and easily manipulated
                                    9
            mechanical stimulations,  such as  sheer  force,  nano-  physical properties.  GelMA is a gelatin substrate that
                                                                               27
            vibration, and shaking to support embryo development.   uses the methacrylic anhydride (MA) reaction to induce
            Nano-vibration culture systems are currently in use for   photocrosslinking.  Therefore, GelMA has sol–gel
                                                                              28
            ARTs.  Previously, mechanical properties of the human   transition properties that can be adjusted by temperature,
                 5
            oviduct have been identified analyzed by JPK NanoWizard   and the methacrylamide and methacrylate side groups
            II AFM (NanoWizard II, JPK, Berlin, Germany) and   on the GelMA chains can manipulate photocrosslinking.
            reported at about 11.5 kPa. 12                     In addition, GelMa supports cell behavior because it has
            Volume 10 Issue 4 (2024)                       446                                doi: 10.36922/ijb.3346
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