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REVIEW ARTICLE

           Advanced 3D-Printing Bioinks for Articular Cartilage

           Repair


           Qiushi Liang 1,2† , Yuanzhu Ma , Xudong Yao *, Wei Wei *
                                                       1,3
                                        2†
                                                                    1,3
           1 International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, China
           2 Zhejiang University-University of Edinburgh Institute, Zhejiang University, Hangzhou, 310000, China
           3 Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of
           Medicine, Hangzhou, 310000, China.
           † These authors contributed equally to this work

           Abstract: Chondral lesions caused by stressors, such as injury or inflammation, lead to osteoarthritis (OA). OA is a degenerative
           joint disease that has become a challenge worldwide. As the articular cartilage is incapable of self-regeneration due to the
           absence of vessels and nerves, novel cartilage repair techniques are urgently needed. Three-dimensional (3D) bioprinting,
           which allows the precise control of internal architecture and geometry of printed scaffolds, has stepped up to be a promising
           strategy in cartilage restoration. With regards to 3D bioprinting, bioinks with proper chemical and mechanical properties play
           one of the most critical roles in designing successful cartilage tissue constructs. In particular, hydrogels as 3D hydrophilic
           cross-linked polymer networks are highly recommended as bioinks because of their fine biocompatibility, easy fabrication,
           and tunable mechanical strength. Herein, we highlight the widely used polymers for hydrogel preparation and further provide
           a non-exhaustive overview of various functional modified additives (such as cells, drugs, bioactive factors and ceramic) to
           exploit the unique properties suitable for bioprinted cartilage. Finally, a prospective on future development for 3D-bioprinting
           in cartilage repair is elucidated in this review.

           Keywords: Osteoarthritis; Hydrogels; Silk fibroin; Collagen; Polyethylene glycol

           *Correspondence to: Xudong Yao, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, No. N1, Shangcheng Avenue, Yiwu,
           322000, China; 0617555@zju.edu.cn; Wei Wei, International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of
           Medicine, Yiwu, China 322000; zjewwei@zju.edu.cn
           Received: January 30, 2022; Accepted: March 11, 2022; Published Online: April 22, 2022

           (This article belongs to the Special Issue: Composite/Multi-component Biomaterial Inks and Bioinks)
           Citation: Liang Q, Ma Y, Yao X, et al., 2022, Advanced 3D-Printing Bioinks for Articular Cartilage Repair. Int J Bioprint, 8(3):511. http://doi.
           org/10.18063/ijb.v8i3.511

           1. Introduction                                     in the synovial joints caused by the progressive loss of
                                                               articular cartilage . Briefly, stressors such as cartilage
                                                                              [4]
           Articular cartilage is  an avascular connective tissue
           that  works  to  lubricate  the  friction  between  the  joint   injury or inflammation may cause the hypersecretion of
           surfaces .  The  only  cell  constituting  this  hyaline   pro-inflammatory cytokines. It promotes the expression
                  [1]
           tissue is the chondrocyte. It is usually embedded in the   of  metalloproteinases  (MMPs)  and  a  disintegrin  and
           extracellular matrix (ECM) mainly consisting of type II   an  MMPs  with  thrombospondin  motifs  (ADAMTS)
           collagen (COL II) network and aggrecan proteoglycan   (Table 4). MMP and ADAMTS enzymes then contribute
           (Table 4) .  The  damage  of  cartilage  may  lead  to   to the decomposition of aggrecan proteoglycan, which
                   [2]
           osteoarthritis (OA) (Table 4), which is the most common   is regarded as a significant early event contributing to
                                                                                                 [2]
           degenerative joint disease that affects over 303 million   the deconstruction of cartilage tissue .  In  addition,
           people  worldwide .  OA  is  characterized  by  severe   collagenases  of  the  MMP  family,  such  as  MMP-13,
                           [3]
           joint pain, swelling, and sound or sensation of grating   lead to the degradation of ECM COL. In turn, the defect
           © 2022 Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and
           reproduction in any medium, provided the original work is properly cited.
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