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International Journal of Bioprinting        3D printed topographically fabricated micron track peripheral nerve conduit



            treatment of PNI using natural and synthetic biomaterials.   alignment, with neuronal axons extending maximally at
            Unfortunately, a significant amount of improvement is still   30–100 μm grooved fibers . Micro-nano topologies have
                                                                                    [28]
            needed to improve peripheral nerve function after surgical   been demonstrated to effectively induce SC migration and
            repair. The failure of artificial nerve conduits is attributed to   orientation without affecting the original physiological
            the slow migration of cells and axons and the disorganized   functions of SCs by Yang  et al.  In addition, micron-
                                                                                         [29]
            growth of new nerve tissue .                       topological track structures can regulate genes involved in
                                 [6]
                                                               myelin formation .
                                                                             [30]
               Treatment of long-distance nerve defects has optimally
            been done with autologous nerve grafting , particularly   It has been found that physisorption or chemical cross-
                                              [7]
            when direct end-to-end suturing is not feasible. There are a   linking can  immobilize  many  biomolecules  on nerve
            few limitations using autologous nerve grafting. First, there   conduits to accelerate nerve regeneration, including nerve
            are only a limited number of sources of the donor’s nerves,   growth factors, DNA, and peptides. These biomolecules,
            and the selection of a donor’s nerve causes the denervation   however,  promote  cell  attachment  and  spreading  but  do
            in the corresponding area. Second, clinical use of the   not regulate cell migration or growth. Hence, the rapid
            donor’s nerve is limited by its differences in dimensions   proliferation of Schwann cells and directional axonal
            from the injured nerve .                           growth can be achieved by introducing both growth factors
                              [8]
                                                               and micron tracks to make suitable nerve conduits.
               For a wide range of nerve regeneration applications,
            nerve conduits have become an alternative to autologous   In this study, a 3D-printed topology micron track
            nerve  grafts  due  to  advancements  in  biomaterials  and   conduit (MTC) was used to repair long-distance PNI with
            designs [9,10] . Many studies aim to promote peripheral   ridge/groove structures and special functional group (-NH ,
                                                                                                            2
            nerve regeneration by increasing the conductivity of   -OH) cues (Figure 1A). The physicochemical properties
            the  conduit .  In  light  of  this,  more  polymer-based   of the prepared hydrogels were investigated, including
                      [11]
            functional nerve-guided conduits are being developed [12,13] .   morphology and stress. Various topological cues and factor
            Furthermore, a variety of methods, including physical,   loading were examined in vitro to determine their synergistic
            chemical, and biological modifications, have been used over   effects on Schwann cell growth (Figure  1B). Interestingly,
            the last decade to modify nerve conduits by manipulating   the MTC had good hemostatic and antimicrobial effects
            the factors that increase Schwann cell migration and   (Figure 1C and D). Additionally, we implanted this conduit
            axonal growth, such as surface charge, functional groups   into a 15-mm sciatic nerve defect in Sprague Dawley
            (-NH , -COOH), surface topography, growth factors, and   (SD) rats in order to systematically evaluate its effect on
                2
            proteins [14,15] . Surface topography plays an important role   nerve regeneration (Figure 1E). To evaluate the effects of
            in guiding the contact of Schwann cells. Multiple studies   the treatment, morphological, immunofluorescence, and
            have demonstrated that ordered tracks regulate Schwann   electrophysiological analyses were conducted. Furthermore,
            cell proliferation, differentiation, and neuronal elongation   the CatWalk method was used to analyze muscle function.
            direction [16,17] . They have found that Schwann cells migrate   For the repair of long-segment peripheral nerve defects, the
            along nerve conduits with directional tracks, which   results of this study will provide an important experimental
            provide the microenvironment for accurate nerve repair.   and theoretical basis. Peripheral nerve regeneration can be
            In  contrast,  lack  of  an  oriented  topography  may  lead  to   improved with the bionic microenvironmental scaffolds
            random growth of nerve tissue and delay regeneration .   currently being developed.
                                                        [9]
            Electrostatic spinning, three-dimensional (3D) printing,
            and microneedle have been used to fabricate topographies   2. Materials and methods
            such as ridge/groove structures, columnar fibers, or   2.1. Materials
            spherical structures on neural implants [18–23] . However,   Chitosan (deacetylation degree 75–85%, molecular weight =
            relatively few studies have shown how uniformly aligned   100,000), acetic acid, acetone, sodium hydroxide, methanol,
            micron tracks influence cell growth, differentiation, and   and acetic anhydride are the products of MACKLIN.
            neural  regeneration .  According  to  several  studies,   Phosphate-buffered saline (PBS) and dulbecco’s modified
                            [24]
            the regeneration of neurons is affected by topology as a   eagle medium (DMEM) were purchased from Cytiva/
            physical factor . For example, PC12 cells can adhere and   Hyclone. Fetal bovine serum (FBS) was purchased from
                       [25]
            orient better to nanogrooved surfaces . Micropatterns on   Serapro.
                                          [26]
            polyester films modified with graphene oxide nanosheets
            promoted the migration of SCs in a directional direction .   2.2. Fabrication of the MTC and MTC@NT3
                                                        [27]
            In the report, SCs migrate fastest along stripes and have   One hundred and forty grams of 4% chitosan was added
            the strongest adhesion between cells. According to   to 3500 ml of 2% acetic acid solution and stirred for 2 h
            Omidinia-Anarkoli et al., grooved fibers facilitate synapse   until all the chitosan was dissolved and filtered through a

            Volume 9 Issue 5 (2023)                        419                         https://doi.org/10.18063/ijb.770
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