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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Chondrocyte spheroid-laden microporous

                                        hydrogel-based 3D bioprinting for cartilage
                                        regeneration



                                        Ruiquan Liu , Litao Jia , Jianguo Chen ,Yi Long , Jinshi Zeng , Siyu Liu , Bo Pan ,
                                                                        1
                                                           2
                                                  1
                                                                                3
                                                                                                           1
                                                                                                    2
                                                                                           1
                                        Xia Liu *, and Haiyue Jiang *
                                              2
                                                               1
                                        1 Department of Auricular Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical
                                        Sciences and Peking Union Medical College, Beijing 100144, China
                                        2 Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking
                                        Union Medical College, Beijing 100144, China
                                        3
                                        Department  of Biomedical  Engineering,  School  of Medicine,  Tsinghua-Peking  Center  for Life
                                        Sciences, Tsinghua University, Beijing 10084, China
                                        Abstract
                                        Three-dimensional (3D) bioprinting has brought new promising strategies for the
                                        regeneration of cartilage with specific shapes. In cartilage bioprinting, chondrocyte-
                                        laden hydrogels are the most commonly used bioinks. However, the dispersion of cells
                                        and the dense texture of the hydrogel in the conventional bioink may limit cell–cell/
                                        cell–extracellular matrix (ECM) interactions, counting against cartilage regeneration
                                        and maturation. To address this issue, in this study, we developed a functional bioink
                                        for  cartilage  bioprinting  based  on  chondrocyte  spheroids  (CSs)  and  microporous
            *Corresponding authors:     hydrogels, in which CSs as multicellular aggregates can provide extensive cell–
            Haiyue Jiang
            (jianghaiyue@psh.pumc.edu.cn)   cell/cell–ECM  interactions  to  mimic  the  natural  cartilage  microenvironment,  and
            Xia Liu                     microporous hydrogels can provide space and channel for the growth and fusion of the
            (liuxia@psh.pumc.edu.cn)    CSs. Firstly, we used a non-adhesive microporous system to produce homogeneous
            Citation: Liu R, Jia L, Chen J,   self-assembled CSs in high-throughput and evaluated the influence of different CSs
            et al., Chondrocyte spheroid-  preparation parameters (cell number and culture time) on CSs, which aids in the
            laden microporous hydrogel-  preparation of bioink suitable for cartilage bioprinting. Then, polyethylene oxide (PEO)
            based 3D bioprinting for cartilage
            regeneration. Int J Bioprint.   was introduced into gelatin methacrylate (GelMA) to prepare microporous hydrogel.
            2024;10(1):0161.            Finally, the CS-laden microporous hydrogels were printed, and the constructs were
            doi: 10.36922/ijb.0161      implanted into nude mice. The results showed that the CSs with 500 cells cultured
            Received: May 11, 2023      for 1 day exhibited better proliferation and growth ability in microporous hydrogels
            Accepted: June 14, 2023     compared  to  those  with  more  cells  and  cultured  for  longer  time.  In  addition,  the
            Published Online: July 28, 2023
                                        results also demonstrated that the CS-laden bioink can be successfully printed into
            Copyright: © 2023 Author(s).   predefined lattice-shape constructs with little cell damage and regenerated cartilage
            This is an Open Access article   tissue  in vivo with a structure similar to natural cartilage characterized by typical
            distributed under the terms of the
            Creative Commons Attribution   lacunae structure and abundant cartilage-specific ECM deposition. In summary, our
            License, permitting distribution,   study verified the feasibility and advantages of using CSs as building blocks in cartilage
            and reproduction in any medium,   bioprinting, which provides novel strategies for the fabrication and regeneration of
            provided the original work is
            properly cited.             patient-specific shaped cartilage.
            Publisher’s Note: AccScience
            Publishing remains neutral with   Keywords: 3D bioprinting; Chondrocyte spheroids; Microporous hydrogels;
            regard to jurisdictional claims in
            published maps and institutional   Cartilage regeneration
            affiliations.


            Volume 10 Issue 1 (2024)                       199                        https://doi.org/10.36922/ijb.0161
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