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International Journal of Bioprinting                                      OMT-loaded spinal cord scaffold



            staining results of the nestin  cells in and around the   in-depth research and try to explore other tissues or organs
                                    +
            lesions  in  the  scaffold  group  and  scaffold  +  OMT  group   that can replace the ECM of the spinal cord.
            indicated that some components of the composite scaffold
            might  positively  affect  the  activation  and  migration  of   5. Conclusion
            endogenous NSCs. In addition, composite scaffolds could   In this study, we fabricated PCL microfiber-reinforced
            induce the differentiation of NSCs toward neurons and   spinal cord ECM hydrogel-based scaffolds loaded with
            promote their maturation. OMT has anti-inflammatory,   OMT. The composite scaffolds promoted the differentiation
            antioxidant, and anti-fibrosis effects. After the occurrence of   of NSCs into neurons and inhibited the differentiation
            SCI, inflammatory mediators and oxidizing substances will   of NSCs into astrocytes. Composite scaffolds provided a
            be produced at the injured site. The addition of OMT may   suitable microenvironment for  in vivo spinal cord tissue
            inhibit further development of inflammation at the injured   regeneration and guided the directional growth of axons.
            site, and reportedly, OMT can promote the repair of SCI.   OMT further promoted nerve regeneration and reduced the
            Thus, the addition of OMT may promote nerve regeneration.  formation of glial scaring around the lesions. In addition, the
               After SCI, astrocytes at the lesion site and around the   transplantation of a scaffold with OMT significantly improved
            lesion usually proliferate and activate in  large quantities   the motor function of rats with SCI. This study suggests a
            to form glial scars , which are undoubtedly a significant   simple way to fabricate advanced materials with the required
                          [53]
            obstacle to the regeneration of the central nervous system.   composition, desirable topographical cues, and excellent
            Most of the previous studies were focused on effectively   therapeutic capability for the clinical treatment of SCI.
            promoting nerve regeneration, whereas only a few studies
            were focused on preventing glial scarring [54,55] . OMT is   Acknowledgments
            a Chinese patented medicine that inhibits the fibrosis of   None.
            various  tissues  and  organs [35,56] .  Relevant  studies  have
            shown that intraperitoneal injection of different doses   Funding
            of OMT could promote recovery from SCI to different
            degrees, but its effect on glial scars is unknown .   This work was supported by National Natural Science
                                                        [36]
            Therefore, we encapsulated OMT into composite scaffolds   Foundation of China (Grant No. 32160209, 82160357
            to explore whether it could inhibit glial scarring. The   and 82071361), and Guangxi Key Laboratory of
            results confirmed that the scaffold + OMT group had the   Basic and Translational Research of Bone and Joint
            least number of GFAP  cells, indicating that OMT plays   Degenerative Diseases, China (Grant No. 21-220-06).
                              +
            a role in inhibiting glial scarring. Unlike previous studies   Department of Education of Guangdong Province, China
            that directly injected OMT into the lesion site to achieve   (2021ZDZX2014), Key Science and Technology Project
            only a short-term drug delivery, we loaded OMT into the   of Social Development Foundation of Dongguan, China
            hydrogel, which avoided its rapid removal from the body   (20211800904542).
            and achieved a sustained release.
                                                               Conflict of interest
               Activation of microglia and production of various
            cytokines after SCI leads to increased inflammatory response   The authors have no conflicts of interest to declare.
            and enhanced activation of TGF-β and Smad2 pathways .
                                                        [57]
            The GF-β/Smad pathway contributes to scar formation   Author contributions
            and plays a role in recovery from injury, but excessive scar   Conceptualization: Yujin Tang, Jia Liu
            tissue formation can interfere with functional recovery .   Formal  analysis: Jing Zhou, Junming Wan, Xingchang
                                                        [58]
            OMT can inhibit the TGF-β/Smad pathway [59,60] . Our study   Zhao, Liqiang Wang
            found an interesting phenomenon, that is, the release of   Investigation: Shiqiang Song, Xingchang Zhao
            OMT affects the differentiation direction of NSCs and   Methodology: Chengliang Yang, Chuanchuan Zheng
            can inhibit the expression of astrocytes, thus reducing the   Supervision: Yujin Tang, Jia Liu
            formation of the glial scar. We speculated that it may be   Writing – original draft: Shiqiang Song
            related to the TGF-β/Smad signaling pathway, which will   Writing – review & editing: Chong Wang, Kai Li
            be further studied in the future.
                                                               Ethics approval and consent to participate
               One drawback of this study is that it is difficult to obtain
            an ECM of the human spinal cord. Therefore, we resorted   The animal experiments in this study were approved
            to using ECM of the spinal cord in rats, which is relatively   and agreed by the Animal Ethics Committee of Youjiang
            easy to obtain. In the future, we will continue to conduct   Medical University for Nationalities.


            Volume 9 Issue 3 (2023)                        115                         https://doi.org/10.18063/ijb.692
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