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International Journal of Bioprinting                            Biocompatible 3D printing photosensitive resin



            plays different roles through p53, JNK, and p38 signaling   addition, the NIPUA photosensitive resin also showed
            pathways [33,34] . When DNA is damaged, GADD45a    good thermal stability and did not deform at 69°C. Most
            upregulation promotes stem cell apoptosis  Furthermore,   importantly, we evaluated the biocompatibility of NIPUA
                                             [35]
            CDKN1a was downregulated in NIPUA compared with the   by comparing it with commercial resins. The commercial
            Trans or White group. CDKN1a is the most widely known   resins demonstrated more pronounced toxicity and may
            cell  cycle  inhibitory  protein  with  the  broadest  kinase   pose a safety hazard during implantation as a surgical
            activity . It is one of the most important downstream   guide, whereas the NIPUA resin has good biocompatibility
                  [36]
            genes of the p53 gene and is a major component in the   in vitro and  in vivo. This paper presents an ingenious
            regulation of cell cycle arrest after DNA damage . Our   method for the fabrication of medical-grade NIPUA from
                                                    [37]
            results indicate that compared to NIPUA, the commercial   renewable materials, broadening the possibility of NIPUA
            resins are highly toxic, which affect the cell cycle and cause   photosensitive  resin  as  a  3D  bioprinting  material  and
            DNA damage.                                        providing important direction for its clinical application.
               In addition, MYC expression level was upregulated in
            NIPUA compared with the Trans or White group. There   Acknowledgments
            is positive feedback between MYC and Wnt signaling   None.
            pathways . Several ligand-membrane receptor pro-
                   [38]
            growth signaling pathways pass through MYC, such   Funding
            as Notch and EGFR [39-41] . Low expression of MYC in   This work was supported by Guangdong Basic and
            commercial resins may activate cell cycle checkpoints,   Applied Basic Research Foundation (2020B1515120075),
            causing cell growth arrest and death or even carcinogenesis.   Key Research and Development Program of Guangzhou
            The  expression  of  PLK1  was  upregulated  in  NIPUA   (202007020002),  and Dongguan  Sci-tech  Commissioner
            compared with the Trans or White group. PLK1 plays an   Program (20221800500032).
            important role in mitosis, participating in centrosome
            migration and spindle assembly [42,43] . There is a negative   Conflict of interest
            feedback regulation between a Fas-associated protein with
            the death domain (FADD) and PLK1. Inhibition of PLK1   The authors declare no conflicts of interest.
            activity impairs autophagy and weakens the interaction
            of  FADD  with  downstream  signaling  proteins  such  as   Author contributions
            caspase-8 . The upregulation of PLK1 levels in the NIPUA   Conceptualization: Zhichao Zheng, Janak L. Pathak
                   [44]
            group reduced malignant cell proliferation and inhibited   Formal analysis: Yan Wang, Zhichao Zheng, Weiwei Feng
            the possibility of carcinogenesis. BUB1b is involved in   Funding acquisition: Huade Zheng
            regulating the spindle assembly checkpoint (SAC) . The   Investigation: Yan Wang, Weicong Wu, Chuangang Yang
                                                    [45]
            SAC maintains genomic stability by delaying cell division   Methodology: Lihong Wu
            and ensuring proper chromosome segregation [46,47] .   Resources: Weiwei Feng, Lihong Wu
            Mutations or abnormal expressions of SAC proteins lead   Project administration: Huade Zheng
            to the development of cancer . BUB1b directly interacts   Supervision: Lihong Wu, Huade Zheng
                                   [48]
            with CDC20 in the mitotic checkpoint complex, thereby   Visualization: Yan Wang
            inhibiting mitotic prophase . Thus, the high expression   Writing – original draft: Yan Wang
                                  [49]
            of BUB1b in the NIPUA group ensured the correct    Writing – review & editing: Janak L. Pathak, Huade Zheng
            chromosome  segregation  and  inhibited  unlimited  cell
            proliferation.                                     Ethics approval and consent to participate

            4. Conclusion                                      All animal experiments were approved by the committee
                                                               of the laboratory animal center at Guangdong Huawei
            In this study, we first synthesized a low-toxic NIPU resin   Testing Co, LTD (No.202209004).
            via the green synthesis method. We investigated the effect
            of different content of PEGDA on the physicochemical   Consent for publication
            properties  of the  photosensitive resin.  A  non-isocyanate
            polyurethane NIPUA with strong mechanical properties,   Not applicable.
            high thermal stability, and good biosafety was obtained.
            When the content of PEGDA was 12 wt.%, NIPUA       Availability of data
            reached its peak in tensile and flexural strength. In   The data will be provided upon reasonable request.



            Volume 9 Issue 3 (2023)                         90                         https://doi.org/10.18063/ijb.684
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