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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        3D-bioprinted RGD-Alg/GelMA/PCL scaffolds

                                        laden with Schwann-like cells for peripheral
                                        nerve reconstruction



                                        Shijun Li 1,2† id , Zichao Wang 1,2† id , Zongxi Wu id , Shang Xie 1,2  id ,
                                                                             3
                                        Xiaofeng Shan 1,2  id , Qing Li * id , and Zhigang Cai * id
                                                               2,4
                                                                                  1,2
                                        1 Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of
                                        Stomatology, Beijing, China
                                        2 National Center for Stomatology & National Clinical Research Center for Oral Diseases & National
                                        Engineering Research Center of Oral Biomaterials and Digital Medical Devices& Beijing Key
                                        Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key
                                        Laboratory for Dental Materials, Beijing, China
                                        3 Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Sun Yat-sen University &
                                        Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China
                                        4 Center for Digital Dentistry, Second Clinical Division, Peking University School and Hospital of
                                        Stomatology, Beijing, China
                                        (This article belongs to the Special Issue: 3D Printing for Tissue Engineering and Regenerative Medicine)


                                        Abstract
                                        Autograft nerve transplantation is widely considered the gold standard for treating
                                        peripheral nerve defects, but it does have certain drawbacks. Alternatively, tissue
            † These authors contributed equally
            to this work.               engineering holds significant promise for nerve regeneration. In this study, three-
                                        dimensional (3D) bioprinting was utilized to fabricate a nerve regenerative conduit
            *Corresponding authors:     with arginine-glycine-aspartic acid-modified sodium alginate (RGD-Alg)/gelatin
            Qing Li
            (qingli@hsc.pku.edu.cn)     methacrylate (GelMA)/polycaprolactone (PCL) laden with induced Schwann-like stem
            Zhigang Cai                 cells from human-exfoliated deciduous teeth (scSHEDs). Stem cells from human-
            (c2013xs@163.com)           exfoliated deciduous teeth (SHEDs) could be stably induced into scSHEDs, as indicated
            Citation: Li S, Wang Z, Wu Z,    by  enhanced  immunofluorescence  staining  for  S-100β,  GFAP,  and  P0  proteins.
            et al. 3D-bioprinted RGD-Alg/  The physical properties of the 6% RGD-Alg/5% GelMA hydrogel were determined
            GelMA/PCL scaffolds laden with   through rheological and maximum tensile testing, displaying decent mechanical and
            Schwann-like cells for peripheral
            nerve reconstruction.       rheological characteristics. Incorporating PCL layers into the hydrogel significantly
            Int J Bioprint. 2024;10(4):2908.    enhanced the scaffold’s physical properties. Live/dead cell staining and nerve growth
            doi: 10.36922/ijb.2908      factor (NGF) release test confirmed the growth of scSHEDs within the 6% RGD-Alg/5%
            Received: February 8, 2024  GelMA hydrogel. S-100β immunofluorescence and cytoskeleton stainings verified the
            Accepted: April 15, 2024    growth of scSHEDs within the scaffold. Eight weeks after anastomosis in rat models
            Published Online: May 13, 2024  with sciatic nerve defects, electrophysiological examination, functional assessment,
            Copyright: © 2024 Author(s).   and immunohistochemical staining were conducted. The results indicated that the
            This is an Open Access article   3D-bioprinted scSHED-laden RGD-Alg/GelMA/PCL scaffold enhanced the efficacy of
            distributed under the terms of the
            Creative Commons Attribution   promoting nerve regeneration compared to the hydrogel and hydrogel/PCL scaffolds.
            License, permitting distribution,   Overall, this study highlighted the potential of scSHEDs and PCL enhancement as viable
            and reproduction in any medium,   improvements to RGD-Alg/GelMA hydrogels for constructing nerve regenerative
            provided the original work is
            properly cited.             conduit. The 3D-bioprinted composite scaffold is expected to provide new insights
                                        into peripheral nerve regeneration and has a wide range of clinical prospects.
            Publisher’s Note: AccScience
            Publishing remains neutral with
            regard to jurisdictional claims in
            published maps and institutional   Keywords: 3D bioprinting; Neural tissue engineering; Schwann-like cells; Stem cells
            affiliations.               from human-exfoliated deciduous teeth; Hydrogel; Polycaprolactone


            Volume 10 Issue 4 (2024)                       459                                doi: 10.36922/ijb.2908
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